Which Factors Might Enhance Safety of Immunotherapy in Your Clinic

David I Bernstein MD FAAAI

Professor of Medicine and Environmental Health

Division of Immunology and Allergy

University of Cincinnati

Disclosures

bull Consultant Merck TEVA Genentech

bull Clinical Research Grants Amgen GlaxoSmithKline Greer Johnson amp Johnson Merck Teva Pfizer Genentech Array Cephalon Novartis BoeringerIngelheim Medimmune

Objectives

1 Recognize factors in an allergy clinic associated with a higher rate of adverse events with subcutaneous AIT

2 Recommend actions that might augment safety of subcutaneous AIT

AAAAIACAAI surveys 39 yr experience of fatal anaphylaxis to allergen injections in North America

83 confirmed fatal reactions1990-2001 1 in 25 million injection visits

or 34 events per year

1973 18 1984 17 1989 41 2001 6 2007 1 2012

Lockey et al Reid et al Bernstein et al Bernstein et al JACI 1987 JACI 1993 JACI 2004 Annals 2010

Number of deaths with SCIT injections

1 confirmed fatal reaction in the US 2008-2011

Safety Factors implicated in fatal SCIT reactions (n=34)

1 Uncontrolled asthma 622 Prior systemic reactions 533 Pollen season 474 Epi delay not given 435 DosingAdmin Errors 356 None reported 177 Inadequate wait 128 Home administration 99 blockersACE Inhibitors 22

Reid M et al JACI 1993 n=17 Bernstein et al JACI 2004 n=17

Lessons Learned in Assessing Risk of SCIT

Fatal Reaction (2009)

bull 43 year old male morbidly obesebull Hx of severe asthma controlled but not on ICSbull Positive prick tests 67 of allergensbull Hypertension AODM lisinopril 40 mg qd x 2 wksbull 110 buildup vialbull Immediate pruritus urticarial angioedema GI

symptoms upperlower airway obstruction hypotension and shock

bull Immediate Treatment 03 mg Epi x 5 (IM) IV fluids tracheostomy by EMS

Epstein et al JACI in practice (in press)

AAAAIACAAI surveillance study (initiated in 2008)

Project AIMS

1 Estimate annual incidence of fatal reactions from

SCIT and skin testing in North America

2 Define relative incidence of systemic allergic

reactions of varying severity

3 Identify clinical practice patterns that may impact

risk of fatal and non-fatal reactions

Bernstein Ann Allergy 2010

Participationndash 4 year study

Population AAAAI and ACAAI member practices prescribing SCIT participation

ndash June 2008 - June 2009 49bull 1922 prescribers of SCIT

ndash August 2009 ndash July 2010 37bull 1453 prescribers

ndash August 2010 ndash August 2011 27

bull 1072 prescribers

ndash September 2011-September 2012 27bull 1073 prescribers

Bernstein et al AAACI 2010 Epstein et al AAACI 2011 2013

WAO Severity Grading of SRs (Years 4 amp5)

bull Grade I Symptom(s) signs of 1 organ system present generalized urticaria withwithout angioedema (NOT laryngeal tongue or uvular) or nausea or upper respiratory symptoms (eg itching of the palate and throat sneezing) or conjunctivalsymptoms

bull Grade 2 Asthma RESPONDING to an inhaled bronchodilator andor GI symptoms including abdominal cramps vomiting or diarrhea or uterine cramps

bull Grade 3 Severe asthma NOT RESPONDING to a bronchodilator or laryngeal uvular or tongue edema with or without stridor

bull Grade 4 Respiratory failure or hypotension with or without loss of consciousness

Modified from Cox JACI 2010

AAAAIACAAI Survey Years 1-4Systemic reaction rate 10000 injection visits

76

23

03

102

67

27

04

97

66

29

04

98

54

23

03 001

8

0

2

4

6

8

10

12

Grade 1 SRs Grade 2 SRs Grade 3 SRs Grade 4 SRs All SRs

Year 1

Year 2

Year 3

Year 4

Epstein et al JACI in practice (in press)

Systemic reactions ndash 01 of injection visits and 14 of injections begin 30 min after injections

4 of all SRs are severe (darrBP airway compromise)

AAAAIACAAI Year 3 Survey

Do you perform pre-injection screening of asthmatics

86

845

1

33

15

42

10

0

10

20

30

40

50

60

70

80

90

100

always often sometimes never

Asthma symptoms

Lung function

N=270 practices

Practices with Grade 3 SRs were no more likely to screen for asthma symptoms than those with only Grade 1 or no SRs

Percent

Epstein et al JACI in

practice (in press)

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

Disclosures

bull Consultant Merck TEVA Genentech

bull Clinical Research Grants Amgen GlaxoSmithKline Greer Johnson amp Johnson Merck Teva Pfizer Genentech Array Cephalon Novartis BoeringerIngelheim Medimmune

Objectives

1 Recognize factors in an allergy clinic associated with a higher rate of adverse events with subcutaneous AIT

2 Recommend actions that might augment safety of subcutaneous AIT

AAAAIACAAI surveys 39 yr experience of fatal anaphylaxis to allergen injections in North America

83 confirmed fatal reactions1990-2001 1 in 25 million injection visits

or 34 events per year

1973 18 1984 17 1989 41 2001 6 2007 1 2012

Lockey et al Reid et al Bernstein et al Bernstein et al JACI 1987 JACI 1993 JACI 2004 Annals 2010

Number of deaths with SCIT injections

1 confirmed fatal reaction in the US 2008-2011

Safety Factors implicated in fatal SCIT reactions (n=34)

1 Uncontrolled asthma 622 Prior systemic reactions 533 Pollen season 474 Epi delay not given 435 DosingAdmin Errors 356 None reported 177 Inadequate wait 128 Home administration 99 blockersACE Inhibitors 22

Reid M et al JACI 1993 n=17 Bernstein et al JACI 2004 n=17

Lessons Learned in Assessing Risk of SCIT

Fatal Reaction (2009)

bull 43 year old male morbidly obesebull Hx of severe asthma controlled but not on ICSbull Positive prick tests 67 of allergensbull Hypertension AODM lisinopril 40 mg qd x 2 wksbull 110 buildup vialbull Immediate pruritus urticarial angioedema GI

symptoms upperlower airway obstruction hypotension and shock

bull Immediate Treatment 03 mg Epi x 5 (IM) IV fluids tracheostomy by EMS

Epstein et al JACI in practice (in press)

AAAAIACAAI surveillance study (initiated in 2008)

Project AIMS

1 Estimate annual incidence of fatal reactions from

SCIT and skin testing in North America

2 Define relative incidence of systemic allergic

reactions of varying severity

3 Identify clinical practice patterns that may impact

risk of fatal and non-fatal reactions

Bernstein Ann Allergy 2010

Participationndash 4 year study

Population AAAAI and ACAAI member practices prescribing SCIT participation

ndash June 2008 - June 2009 49bull 1922 prescribers of SCIT

ndash August 2009 ndash July 2010 37bull 1453 prescribers

ndash August 2010 ndash August 2011 27

bull 1072 prescribers

ndash September 2011-September 2012 27bull 1073 prescribers

Bernstein et al AAACI 2010 Epstein et al AAACI 2011 2013

WAO Severity Grading of SRs (Years 4 amp5)

bull Grade I Symptom(s) signs of 1 organ system present generalized urticaria withwithout angioedema (NOT laryngeal tongue or uvular) or nausea or upper respiratory symptoms (eg itching of the palate and throat sneezing) or conjunctivalsymptoms

bull Grade 2 Asthma RESPONDING to an inhaled bronchodilator andor GI symptoms including abdominal cramps vomiting or diarrhea or uterine cramps

bull Grade 3 Severe asthma NOT RESPONDING to a bronchodilator or laryngeal uvular or tongue edema with or without stridor

bull Grade 4 Respiratory failure or hypotension with or without loss of consciousness

Modified from Cox JACI 2010

AAAAIACAAI Survey Years 1-4Systemic reaction rate 10000 injection visits

76

23

03

102

67

27

04

97

66

29

04

98

54

23

03 001

8

0

2

4

6

8

10

12

Grade 1 SRs Grade 2 SRs Grade 3 SRs Grade 4 SRs All SRs

Year 1

Year 2

Year 3

Year 4

Epstein et al JACI in practice (in press)

Systemic reactions ndash 01 of injection visits and 14 of injections begin 30 min after injections

4 of all SRs are severe (darrBP airway compromise)

AAAAIACAAI Year 3 Survey

Do you perform pre-injection screening of asthmatics

86

845

1

33

15

42

10

0

10

20

30

40

50

60

70

80

90

100

always often sometimes never

Asthma symptoms

Lung function

N=270 practices

Practices with Grade 3 SRs were no more likely to screen for asthma symptoms than those with only Grade 1 or no SRs

Percent

Epstein et al JACI in

practice (in press)

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

Objectives

1 Recognize factors in an allergy clinic associated with a higher rate of adverse events with subcutaneous AIT

2 Recommend actions that might augment safety of subcutaneous AIT

AAAAIACAAI surveys 39 yr experience of fatal anaphylaxis to allergen injections in North America

83 confirmed fatal reactions1990-2001 1 in 25 million injection visits

or 34 events per year

1973 18 1984 17 1989 41 2001 6 2007 1 2012

Lockey et al Reid et al Bernstein et al Bernstein et al JACI 1987 JACI 1993 JACI 2004 Annals 2010

Number of deaths with SCIT injections

1 confirmed fatal reaction in the US 2008-2011

Safety Factors implicated in fatal SCIT reactions (n=34)

1 Uncontrolled asthma 622 Prior systemic reactions 533 Pollen season 474 Epi delay not given 435 DosingAdmin Errors 356 None reported 177 Inadequate wait 128 Home administration 99 blockersACE Inhibitors 22

Reid M et al JACI 1993 n=17 Bernstein et al JACI 2004 n=17

Lessons Learned in Assessing Risk of SCIT

Fatal Reaction (2009)

bull 43 year old male morbidly obesebull Hx of severe asthma controlled but not on ICSbull Positive prick tests 67 of allergensbull Hypertension AODM lisinopril 40 mg qd x 2 wksbull 110 buildup vialbull Immediate pruritus urticarial angioedema GI

symptoms upperlower airway obstruction hypotension and shock

bull Immediate Treatment 03 mg Epi x 5 (IM) IV fluids tracheostomy by EMS

Epstein et al JACI in practice (in press)

AAAAIACAAI surveillance study (initiated in 2008)

Project AIMS

1 Estimate annual incidence of fatal reactions from

SCIT and skin testing in North America

2 Define relative incidence of systemic allergic

reactions of varying severity

3 Identify clinical practice patterns that may impact

risk of fatal and non-fatal reactions

Bernstein Ann Allergy 2010

Participationndash 4 year study

Population AAAAI and ACAAI member practices prescribing SCIT participation

ndash June 2008 - June 2009 49bull 1922 prescribers of SCIT

ndash August 2009 ndash July 2010 37bull 1453 prescribers

ndash August 2010 ndash August 2011 27

bull 1072 prescribers

ndash September 2011-September 2012 27bull 1073 prescribers

Bernstein et al AAACI 2010 Epstein et al AAACI 2011 2013

WAO Severity Grading of SRs (Years 4 amp5)

bull Grade I Symptom(s) signs of 1 organ system present generalized urticaria withwithout angioedema (NOT laryngeal tongue or uvular) or nausea or upper respiratory symptoms (eg itching of the palate and throat sneezing) or conjunctivalsymptoms

bull Grade 2 Asthma RESPONDING to an inhaled bronchodilator andor GI symptoms including abdominal cramps vomiting or diarrhea or uterine cramps

bull Grade 3 Severe asthma NOT RESPONDING to a bronchodilator or laryngeal uvular or tongue edema with or without stridor

bull Grade 4 Respiratory failure or hypotension with or without loss of consciousness

Modified from Cox JACI 2010

AAAAIACAAI Survey Years 1-4Systemic reaction rate 10000 injection visits

76

23

03

102

67

27

04

97

66

29

04

98

54

23

03 001

8

0

2

4

6

8

10

12

Grade 1 SRs Grade 2 SRs Grade 3 SRs Grade 4 SRs All SRs

Year 1

Year 2

Year 3

Year 4

Epstein et al JACI in practice (in press)

Systemic reactions ndash 01 of injection visits and 14 of injections begin 30 min after injections

4 of all SRs are severe (darrBP airway compromise)

AAAAIACAAI Year 3 Survey

Do you perform pre-injection screening of asthmatics

86

845

1

33

15

42

10

0

10

20

30

40

50

60

70

80

90

100

always often sometimes never

Asthma symptoms

Lung function

N=270 practices

Practices with Grade 3 SRs were no more likely to screen for asthma symptoms than those with only Grade 1 or no SRs

Percent

Epstein et al JACI in

practice (in press)

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

AAAAIACAAI surveys 39 yr experience of fatal anaphylaxis to allergen injections in North America

83 confirmed fatal reactions1990-2001 1 in 25 million injection visits

or 34 events per year

1973 18 1984 17 1989 41 2001 6 2007 1 2012

Lockey et al Reid et al Bernstein et al Bernstein et al JACI 1987 JACI 1993 JACI 2004 Annals 2010

Number of deaths with SCIT injections

1 confirmed fatal reaction in the US 2008-2011

Safety Factors implicated in fatal SCIT reactions (n=34)

1 Uncontrolled asthma 622 Prior systemic reactions 533 Pollen season 474 Epi delay not given 435 DosingAdmin Errors 356 None reported 177 Inadequate wait 128 Home administration 99 blockersACE Inhibitors 22

Reid M et al JACI 1993 n=17 Bernstein et al JACI 2004 n=17

Lessons Learned in Assessing Risk of SCIT

Fatal Reaction (2009)

bull 43 year old male morbidly obesebull Hx of severe asthma controlled but not on ICSbull Positive prick tests 67 of allergensbull Hypertension AODM lisinopril 40 mg qd x 2 wksbull 110 buildup vialbull Immediate pruritus urticarial angioedema GI

symptoms upperlower airway obstruction hypotension and shock

bull Immediate Treatment 03 mg Epi x 5 (IM) IV fluids tracheostomy by EMS

Epstein et al JACI in practice (in press)

AAAAIACAAI surveillance study (initiated in 2008)

Project AIMS

1 Estimate annual incidence of fatal reactions from

SCIT and skin testing in North America

2 Define relative incidence of systemic allergic

reactions of varying severity

3 Identify clinical practice patterns that may impact

risk of fatal and non-fatal reactions

Bernstein Ann Allergy 2010

Participationndash 4 year study

Population AAAAI and ACAAI member practices prescribing SCIT participation

ndash June 2008 - June 2009 49bull 1922 prescribers of SCIT

ndash August 2009 ndash July 2010 37bull 1453 prescribers

ndash August 2010 ndash August 2011 27

bull 1072 prescribers

ndash September 2011-September 2012 27bull 1073 prescribers

Bernstein et al AAACI 2010 Epstein et al AAACI 2011 2013

WAO Severity Grading of SRs (Years 4 amp5)

bull Grade I Symptom(s) signs of 1 organ system present generalized urticaria withwithout angioedema (NOT laryngeal tongue or uvular) or nausea or upper respiratory symptoms (eg itching of the palate and throat sneezing) or conjunctivalsymptoms

bull Grade 2 Asthma RESPONDING to an inhaled bronchodilator andor GI symptoms including abdominal cramps vomiting or diarrhea or uterine cramps

bull Grade 3 Severe asthma NOT RESPONDING to a bronchodilator or laryngeal uvular or tongue edema with or without stridor

bull Grade 4 Respiratory failure or hypotension with or without loss of consciousness

Modified from Cox JACI 2010

AAAAIACAAI Survey Years 1-4Systemic reaction rate 10000 injection visits

76

23

03

102

67

27

04

97

66

29

04

98

54

23

03 001

8

0

2

4

6

8

10

12

Grade 1 SRs Grade 2 SRs Grade 3 SRs Grade 4 SRs All SRs

Year 1

Year 2

Year 3

Year 4

Epstein et al JACI in practice (in press)

Systemic reactions ndash 01 of injection visits and 14 of injections begin 30 min after injections

4 of all SRs are severe (darrBP airway compromise)

AAAAIACAAI Year 3 Survey

Do you perform pre-injection screening of asthmatics

86

845

1

33

15

42

10

0

10

20

30

40

50

60

70

80

90

100

always often sometimes never

Asthma symptoms

Lung function

N=270 practices

Practices with Grade 3 SRs were no more likely to screen for asthma symptoms than those with only Grade 1 or no SRs

Percent

Epstein et al JACI in

practice (in press)

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

Safety Factors implicated in fatal SCIT reactions (n=34)

1 Uncontrolled asthma 622 Prior systemic reactions 533 Pollen season 474 Epi delay not given 435 DosingAdmin Errors 356 None reported 177 Inadequate wait 128 Home administration 99 blockersACE Inhibitors 22

Reid M et al JACI 1993 n=17 Bernstein et al JACI 2004 n=17

Lessons Learned in Assessing Risk of SCIT

Fatal Reaction (2009)

bull 43 year old male morbidly obesebull Hx of severe asthma controlled but not on ICSbull Positive prick tests 67 of allergensbull Hypertension AODM lisinopril 40 mg qd x 2 wksbull 110 buildup vialbull Immediate pruritus urticarial angioedema GI

symptoms upperlower airway obstruction hypotension and shock

bull Immediate Treatment 03 mg Epi x 5 (IM) IV fluids tracheostomy by EMS

Epstein et al JACI in practice (in press)

AAAAIACAAI surveillance study (initiated in 2008)

Project AIMS

1 Estimate annual incidence of fatal reactions from

SCIT and skin testing in North America

2 Define relative incidence of systemic allergic

reactions of varying severity

3 Identify clinical practice patterns that may impact

risk of fatal and non-fatal reactions

Bernstein Ann Allergy 2010

Participationndash 4 year study

Population AAAAI and ACAAI member practices prescribing SCIT participation

ndash June 2008 - June 2009 49bull 1922 prescribers of SCIT

ndash August 2009 ndash July 2010 37bull 1453 prescribers

ndash August 2010 ndash August 2011 27

bull 1072 prescribers

ndash September 2011-September 2012 27bull 1073 prescribers

Bernstein et al AAACI 2010 Epstein et al AAACI 2011 2013

WAO Severity Grading of SRs (Years 4 amp5)

bull Grade I Symptom(s) signs of 1 organ system present generalized urticaria withwithout angioedema (NOT laryngeal tongue or uvular) or nausea or upper respiratory symptoms (eg itching of the palate and throat sneezing) or conjunctivalsymptoms

bull Grade 2 Asthma RESPONDING to an inhaled bronchodilator andor GI symptoms including abdominal cramps vomiting or diarrhea or uterine cramps

bull Grade 3 Severe asthma NOT RESPONDING to a bronchodilator or laryngeal uvular or tongue edema with or without stridor

bull Grade 4 Respiratory failure or hypotension with or without loss of consciousness

Modified from Cox JACI 2010

AAAAIACAAI Survey Years 1-4Systemic reaction rate 10000 injection visits

76

23

03

102

67

27

04

97

66

29

04

98

54

23

03 001

8

0

2

4

6

8

10

12

Grade 1 SRs Grade 2 SRs Grade 3 SRs Grade 4 SRs All SRs

Year 1

Year 2

Year 3

Year 4

Epstein et al JACI in practice (in press)

Systemic reactions ndash 01 of injection visits and 14 of injections begin 30 min after injections

4 of all SRs are severe (darrBP airway compromise)

AAAAIACAAI Year 3 Survey

Do you perform pre-injection screening of asthmatics

86

845

1

33

15

42

10

0

10

20

30

40

50

60

70

80

90

100

always often sometimes never

Asthma symptoms

Lung function

N=270 practices

Practices with Grade 3 SRs were no more likely to screen for asthma symptoms than those with only Grade 1 or no SRs

Percent

Epstein et al JACI in

practice (in press)

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

Lessons Learned in Assessing Risk of SCIT

Fatal Reaction (2009)

bull 43 year old male morbidly obesebull Hx of severe asthma controlled but not on ICSbull Positive prick tests 67 of allergensbull Hypertension AODM lisinopril 40 mg qd x 2 wksbull 110 buildup vialbull Immediate pruritus urticarial angioedema GI

symptoms upperlower airway obstruction hypotension and shock

bull Immediate Treatment 03 mg Epi x 5 (IM) IV fluids tracheostomy by EMS

Epstein et al JACI in practice (in press)

AAAAIACAAI surveillance study (initiated in 2008)

Project AIMS

1 Estimate annual incidence of fatal reactions from

SCIT and skin testing in North America

2 Define relative incidence of systemic allergic

reactions of varying severity

3 Identify clinical practice patterns that may impact

risk of fatal and non-fatal reactions

Bernstein Ann Allergy 2010

Participationndash 4 year study

Population AAAAI and ACAAI member practices prescribing SCIT participation

ndash June 2008 - June 2009 49bull 1922 prescribers of SCIT

ndash August 2009 ndash July 2010 37bull 1453 prescribers

ndash August 2010 ndash August 2011 27

bull 1072 prescribers

ndash September 2011-September 2012 27bull 1073 prescribers

Bernstein et al AAACI 2010 Epstein et al AAACI 2011 2013

WAO Severity Grading of SRs (Years 4 amp5)

bull Grade I Symptom(s) signs of 1 organ system present generalized urticaria withwithout angioedema (NOT laryngeal tongue or uvular) or nausea or upper respiratory symptoms (eg itching of the palate and throat sneezing) or conjunctivalsymptoms

bull Grade 2 Asthma RESPONDING to an inhaled bronchodilator andor GI symptoms including abdominal cramps vomiting or diarrhea or uterine cramps

bull Grade 3 Severe asthma NOT RESPONDING to a bronchodilator or laryngeal uvular or tongue edema with or without stridor

bull Grade 4 Respiratory failure or hypotension with or without loss of consciousness

Modified from Cox JACI 2010

AAAAIACAAI Survey Years 1-4Systemic reaction rate 10000 injection visits

76

23

03

102

67

27

04

97

66

29

04

98

54

23

03 001

8

0

2

4

6

8

10

12

Grade 1 SRs Grade 2 SRs Grade 3 SRs Grade 4 SRs All SRs

Year 1

Year 2

Year 3

Year 4

Epstein et al JACI in practice (in press)

Systemic reactions ndash 01 of injection visits and 14 of injections begin 30 min after injections

4 of all SRs are severe (darrBP airway compromise)

AAAAIACAAI Year 3 Survey

Do you perform pre-injection screening of asthmatics

86

845

1

33

15

42

10

0

10

20

30

40

50

60

70

80

90

100

always often sometimes never

Asthma symptoms

Lung function

N=270 practices

Practices with Grade 3 SRs were no more likely to screen for asthma symptoms than those with only Grade 1 or no SRs

Percent

Epstein et al JACI in

practice (in press)

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

Fatal Reaction (2009)

bull 43 year old male morbidly obesebull Hx of severe asthma controlled but not on ICSbull Positive prick tests 67 of allergensbull Hypertension AODM lisinopril 40 mg qd x 2 wksbull 110 buildup vialbull Immediate pruritus urticarial angioedema GI

symptoms upperlower airway obstruction hypotension and shock

bull Immediate Treatment 03 mg Epi x 5 (IM) IV fluids tracheostomy by EMS

Epstein et al JACI in practice (in press)

AAAAIACAAI surveillance study (initiated in 2008)

Project AIMS

1 Estimate annual incidence of fatal reactions from

SCIT and skin testing in North America

2 Define relative incidence of systemic allergic

reactions of varying severity

3 Identify clinical practice patterns that may impact

risk of fatal and non-fatal reactions

Bernstein Ann Allergy 2010

Participationndash 4 year study

Population AAAAI and ACAAI member practices prescribing SCIT participation

ndash June 2008 - June 2009 49bull 1922 prescribers of SCIT

ndash August 2009 ndash July 2010 37bull 1453 prescribers

ndash August 2010 ndash August 2011 27

bull 1072 prescribers

ndash September 2011-September 2012 27bull 1073 prescribers

Bernstein et al AAACI 2010 Epstein et al AAACI 2011 2013

WAO Severity Grading of SRs (Years 4 amp5)

bull Grade I Symptom(s) signs of 1 organ system present generalized urticaria withwithout angioedema (NOT laryngeal tongue or uvular) or nausea or upper respiratory symptoms (eg itching of the palate and throat sneezing) or conjunctivalsymptoms

bull Grade 2 Asthma RESPONDING to an inhaled bronchodilator andor GI symptoms including abdominal cramps vomiting or diarrhea or uterine cramps

bull Grade 3 Severe asthma NOT RESPONDING to a bronchodilator or laryngeal uvular or tongue edema with or without stridor

bull Grade 4 Respiratory failure or hypotension with or without loss of consciousness

Modified from Cox JACI 2010

AAAAIACAAI Survey Years 1-4Systemic reaction rate 10000 injection visits

76

23

03

102

67

27

04

97

66

29

04

98

54

23

03 001

8

0

2

4

6

8

10

12

Grade 1 SRs Grade 2 SRs Grade 3 SRs Grade 4 SRs All SRs

Year 1

Year 2

Year 3

Year 4

Epstein et al JACI in practice (in press)

Systemic reactions ndash 01 of injection visits and 14 of injections begin 30 min after injections

4 of all SRs are severe (darrBP airway compromise)

AAAAIACAAI Year 3 Survey

Do you perform pre-injection screening of asthmatics

86

845

1

33

15

42

10

0

10

20

30

40

50

60

70

80

90

100

always often sometimes never

Asthma symptoms

Lung function

N=270 practices

Practices with Grade 3 SRs were no more likely to screen for asthma symptoms than those with only Grade 1 or no SRs

Percent

Epstein et al JACI in

practice (in press)

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

AAAAIACAAI surveillance study (initiated in 2008)

Project AIMS

1 Estimate annual incidence of fatal reactions from

SCIT and skin testing in North America

2 Define relative incidence of systemic allergic

reactions of varying severity

3 Identify clinical practice patterns that may impact

risk of fatal and non-fatal reactions

Bernstein Ann Allergy 2010

Participationndash 4 year study

Population AAAAI and ACAAI member practices prescribing SCIT participation

ndash June 2008 - June 2009 49bull 1922 prescribers of SCIT

ndash August 2009 ndash July 2010 37bull 1453 prescribers

ndash August 2010 ndash August 2011 27

bull 1072 prescribers

ndash September 2011-September 2012 27bull 1073 prescribers

Bernstein et al AAACI 2010 Epstein et al AAACI 2011 2013

WAO Severity Grading of SRs (Years 4 amp5)

bull Grade I Symptom(s) signs of 1 organ system present generalized urticaria withwithout angioedema (NOT laryngeal tongue or uvular) or nausea or upper respiratory symptoms (eg itching of the palate and throat sneezing) or conjunctivalsymptoms

bull Grade 2 Asthma RESPONDING to an inhaled bronchodilator andor GI symptoms including abdominal cramps vomiting or diarrhea or uterine cramps

bull Grade 3 Severe asthma NOT RESPONDING to a bronchodilator or laryngeal uvular or tongue edema with or without stridor

bull Grade 4 Respiratory failure or hypotension with or without loss of consciousness

Modified from Cox JACI 2010

AAAAIACAAI Survey Years 1-4Systemic reaction rate 10000 injection visits

76

23

03

102

67

27

04

97

66

29

04

98

54

23

03 001

8

0

2

4

6

8

10

12

Grade 1 SRs Grade 2 SRs Grade 3 SRs Grade 4 SRs All SRs

Year 1

Year 2

Year 3

Year 4

Epstein et al JACI in practice (in press)

Systemic reactions ndash 01 of injection visits and 14 of injections begin 30 min after injections

4 of all SRs are severe (darrBP airway compromise)

AAAAIACAAI Year 3 Survey

Do you perform pre-injection screening of asthmatics

86

845

1

33

15

42

10

0

10

20

30

40

50

60

70

80

90

100

always often sometimes never

Asthma symptoms

Lung function

N=270 practices

Practices with Grade 3 SRs were no more likely to screen for asthma symptoms than those with only Grade 1 or no SRs

Percent

Epstein et al JACI in

practice (in press)

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

Participationndash 4 year study

Population AAAAI and ACAAI member practices prescribing SCIT participation

ndash June 2008 - June 2009 49bull 1922 prescribers of SCIT

ndash August 2009 ndash July 2010 37bull 1453 prescribers

ndash August 2010 ndash August 2011 27

bull 1072 prescribers

ndash September 2011-September 2012 27bull 1073 prescribers

Bernstein et al AAACI 2010 Epstein et al AAACI 2011 2013

WAO Severity Grading of SRs (Years 4 amp5)

bull Grade I Symptom(s) signs of 1 organ system present generalized urticaria withwithout angioedema (NOT laryngeal tongue or uvular) or nausea or upper respiratory symptoms (eg itching of the palate and throat sneezing) or conjunctivalsymptoms

bull Grade 2 Asthma RESPONDING to an inhaled bronchodilator andor GI symptoms including abdominal cramps vomiting or diarrhea or uterine cramps

bull Grade 3 Severe asthma NOT RESPONDING to a bronchodilator or laryngeal uvular or tongue edema with or without stridor

bull Grade 4 Respiratory failure or hypotension with or without loss of consciousness

Modified from Cox JACI 2010

AAAAIACAAI Survey Years 1-4Systemic reaction rate 10000 injection visits

76

23

03

102

67

27

04

97

66

29

04

98

54

23

03 001

8

0

2

4

6

8

10

12

Grade 1 SRs Grade 2 SRs Grade 3 SRs Grade 4 SRs All SRs

Year 1

Year 2

Year 3

Year 4

Epstein et al JACI in practice (in press)

Systemic reactions ndash 01 of injection visits and 14 of injections begin 30 min after injections

4 of all SRs are severe (darrBP airway compromise)

AAAAIACAAI Year 3 Survey

Do you perform pre-injection screening of asthmatics

86

845

1

33

15

42

10

0

10

20

30

40

50

60

70

80

90

100

always often sometimes never

Asthma symptoms

Lung function

N=270 practices

Practices with Grade 3 SRs were no more likely to screen for asthma symptoms than those with only Grade 1 or no SRs

Percent

Epstein et al JACI in

practice (in press)

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

WAO Severity Grading of SRs (Years 4 amp5)

bull Grade I Symptom(s) signs of 1 organ system present generalized urticaria withwithout angioedema (NOT laryngeal tongue or uvular) or nausea or upper respiratory symptoms (eg itching of the palate and throat sneezing) or conjunctivalsymptoms

bull Grade 2 Asthma RESPONDING to an inhaled bronchodilator andor GI symptoms including abdominal cramps vomiting or diarrhea or uterine cramps

bull Grade 3 Severe asthma NOT RESPONDING to a bronchodilator or laryngeal uvular or tongue edema with or without stridor

bull Grade 4 Respiratory failure or hypotension with or without loss of consciousness

Modified from Cox JACI 2010

AAAAIACAAI Survey Years 1-4Systemic reaction rate 10000 injection visits

76

23

03

102

67

27

04

97

66

29

04

98

54

23

03 001

8

0

2

4

6

8

10

12

Grade 1 SRs Grade 2 SRs Grade 3 SRs Grade 4 SRs All SRs

Year 1

Year 2

Year 3

Year 4

Epstein et al JACI in practice (in press)

Systemic reactions ndash 01 of injection visits and 14 of injections begin 30 min after injections

4 of all SRs are severe (darrBP airway compromise)

AAAAIACAAI Year 3 Survey

Do you perform pre-injection screening of asthmatics

86

845

1

33

15

42

10

0

10

20

30

40

50

60

70

80

90

100

always often sometimes never

Asthma symptoms

Lung function

N=270 practices

Practices with Grade 3 SRs were no more likely to screen for asthma symptoms than those with only Grade 1 or no SRs

Percent

Epstein et al JACI in

practice (in press)

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

AAAAIACAAI Survey Years 1-4Systemic reaction rate 10000 injection visits

76

23

03

102

67

27

04

97

66

29

04

98

54

23

03 001

8

0

2

4

6

8

10

12

Grade 1 SRs Grade 2 SRs Grade 3 SRs Grade 4 SRs All SRs

Year 1

Year 2

Year 3

Year 4

Epstein et al JACI in practice (in press)

Systemic reactions ndash 01 of injection visits and 14 of injections begin 30 min after injections

4 of all SRs are severe (darrBP airway compromise)

AAAAIACAAI Year 3 Survey

Do you perform pre-injection screening of asthmatics

86

845

1

33

15

42

10

0

10

20

30

40

50

60

70

80

90

100

always often sometimes never

Asthma symptoms

Lung function

N=270 practices

Practices with Grade 3 SRs were no more likely to screen for asthma symptoms than those with only Grade 1 or no SRs

Percent

Epstein et al JACI in

practice (in press)

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

AAAAIACAAI Year 3 Survey

Do you perform pre-injection screening of asthmatics

86

845

1

33

15

42

10

0

10

20

30

40

50

60

70

80

90

100

always often sometimes never

Asthma symptoms

Lung function

N=270 practices

Practices with Grade 3 SRs were no more likely to screen for asthma symptoms than those with only Grade 1 or no SRs

Percent

Epstein et al JACI in

practice (in press)

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

Does adjusting doses during peak pollen seasons impact SR rates (Year 4 n=235)

Epstein et al JACI in practice (in press)

29 30

14

12

0

5

10

15

20

25

30

35

Build-up (129 SRs) Maintenance (126 SRs)

Pe

rce

nt

of

pra

ctic

es

Never Adjust

SometimesOften orAlways Adjust

Grade 3 or 4 SRsplt0001

Practices never reducing doses during peak pollen seasons in build-up or maintenance vials were significantly more likely to report Grade 3 or 4 SRs

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

Pollen seasons during which SRs occurred (Year 4 n=200 practices)

Epstein et al JACI in practice (in press)

24

23

123

35

Grass

Trees

Weeds

Other Pollen Season

Not during pollenseason

There were significantly more SRs during

Grass and Tree Season combined plt0001

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

AAAAIACAAI Year 4 SurveyNumber of practices using various build-up strategies

268 practices= 93 of patients

73 practices= 46 of patients 32 practices=

21 of patients

6 practices=05 of patients

0

50

100

150

200

250

300

Conventional build-up

Cluster build-up Rush build-up Other

As in Year 3 Cluster and Rush Build-up were associated with an increased risk of

Systemic Reactions (plt0001)

Epstein et al JACI in practice (in press)

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

What clinical practices decrease the risk of SRs associated with cluster and rush

(Year 4 n=74 practices)

bull Pre-medication did not lower the risk of SRs (p=02)

bull Practices with an earlier change to conventional SCIT had fewer SRs (168 per practice vs 353 per

practice) but this was not significant (p=02)

ndash There was a trend suggesting that an earlier change to conventional SCIT was associated with fewer Grade 3 SRs (p=007)

Epstein et al JACI in practice (in press)

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

IT Practice Parameter 3rd update ndash ACE Inhibitors

bull Summary Statement 40 ACE inhibitors have been associated with greater risk for more severe reaction from venom IT and field stings ACE inhibitor discontinuation should be considered for patients receiving venom immunotherapy No enhanced risk in patients on aeroallergen IT JACI Immunotherapy Practice Parameter 2011 3rd update

ndash Case reports of anaphylaxis with VIT in 2 pts on ACE INH tolerated injections after discontinuing drug

ndash Risk for severe anaphylaxis to VIT in pts treated with ACE INH was confirmed in a prospective study

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

1 Action plan for managing late onset systemic reactions (self-injectable EPI in high risk pts)

2 Reduce doses during patientsrsquo peak pollen season3 Exclusion of at high risk patients prior anaphylaxis severe

poorly controlled asthma cardiac disease4 Universal pre-injection screening for asthma control

(symptoms plusmn lung function)5 30 minute post-injection observation period6 Facility prepared to immediately treat anaphylaxis with

epinephrine especially during accelerated build-up7 Double check patients ID (eg birth date)8 Avoidance of ACE inhibitors for venom AIT

bull What high dose ACEi in patients receiving aeroallergen SCIT

Clinical Practice Recommendations

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

Acknowledgements IT Surveillance Project

1 Funded by ACAAI and AAAAI grants

2 AAAAIACAAI participants

3 ImmunotherapyDiagnostics Committees

ndash Support and sponsorship

4 Karen Murphy BS CCRN

ndash Research coordinator data collection

5 Tolly Epstein MD MS Gary M Liss MD MS Data analysis manuscript preparation

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol

References 1 Lockey RF Benedict LM Turkeltaub PC Bukantz SC Fatalities from immunotherapy (IT) and skin testing (ST) J Allergy Clin

Immunol 1987 79660-77

2 Bernstein DI Wanner M Borish L Liss GM Twelve-year survey of fatal reactions to allergen injections and skin testing 1990-2001 J Allergy Clin Immunol 2004 1131129-36

3 Reid MJ Lockey RF Turkeltaub PC Platts-Mills TA Survey of fatalities from skin testing and immunotherapy 1985-1989 J Allergy Clin Immunol 1993 926-15

4 Amin HS Liss GM Bernstein DI Evaluation of near-fatal reactions to allergen immunotherapy injections J Allergy Clin Immunol 2006 117169-75

5 Bernstein DI Epstein T Murphy-Berendts K Liss GM Surveillance of systemic reactions to subcutaneous immunotherapy injections year 1 outcomes of the ACAAI and AAAAI collaborative studyAnn Allergy Asthma Immunol 2010 Jun104(6)530-5

6 Liss GM Murphy-Berendts K Epstein T Bernstein DI Factors associated with severe versus mild immunotherapy-related systemic reactionsA case-referent studyJ Allergy Clin Immunol2011 May127(5)1298-300

7 Cox L Nelson H Lockey R et al Allergen immunotherapy a practice parameter third update J Allergy Clin Immunol 2011 Jan127(1 Suppl)S1-55

8 Nelson H Nolte H Creticos P Maloney J Wu J and Bernstein D Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults (J Allergy Clin Immunol 201112772-80)

9 Epstein TG Liss GM Murphy-Berendts K Bernstein DIAnn Allergy Asthma Immunol Immediate and delayed-onset systemic reactions after subcutaneous immunotherapy injections ACAAIAAAAI surveillance study of subcutaneous immunotherapy-year 2 2011 Nov107(5)426-431e1 Epub 2011 Jun 17

10 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAI and ACAAI surveillance study of subcutaneous immunotherapy Year 3 what practices modify the risk of systemic reactions Ann Allergy Asthma Immunol2013110274-8 8 e1

11 Epstein TG Liss GM Murphy-Berendts K Bernstein DI AAAAIACAAI Surveillance Study of Subcutaneous Immunotherapy ndash Year 4 JACI in practice (in press)

bull Tol