SLE Discussion Topics

The Path to Diagnosis

Pathogenesis

Impact on Patients: Mortality and Morbidity

The Burden of Lupus

Patient Support

2

The Path to Diagnosis

SLE Is an Autoimmune Disease That Primarily Affects Women of Childbearing Age

SLE is a chronic, multisystem autoimmune disease characterized by:1

Diverse clinical manifestations, which are the result of inflammation in affected organ systems2

Being potentially life threatening when major organs are affected1

Waxing and waning disease activity1

SLE patient population:

Nine out of 10 cases occur in women,3 with the majority diagnosed between 15 and 45 years of age4

Tends to be more severe in men vs women5

More common and severe among nonwhite populations6-9*

4

*Nonwhite populations include those of African, Asian, Australian Aboriginal, Hispanic, and Native American descent.

1. ACR Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 1999;42:17851796. 2. Wallace DJ, Hahn B, eds. Dubois' Lupus Erythmatosus. 7th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2007. 3. DCruz DP, et al. Lancet. 2007;369:587596. 4. Cervera R, et al. Medicine. 1993;72:113-124. 5. Tan TC, et al. J Rheumatol. 2012;39:759-769. 6. Samanta A, et al. Ann Rheum Dis. 1991;50(7):490-492. 7. Boyer GS, et al. J Rheumatol. 1991;18:1477-1484. 8. Bossingham D. Lupus. 2003;12:327-331. 9. Fernandez M, et al. Arthritis Rheum. 2007;57(4):576-584.

A Range of Organ Systems May Be Involved

ACR Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 1999;42:1785-1796.

Central Nervous System

Eyes and Mucous Membranes

Kidneys

GastrointestinalMusculoskeletal

Hematologic

Skin Heart and Lungs

5

1. ACR Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 1999;42:1785-1796. 2. Heinlen LD, et al. Arthritis Rheum. 2007;56:2344-2351.

3. ACR Ad Hoc Committee on Neuropsychiatric Lupus Nomenclature. Arthritis Rheum. 1999;42:599-608.

American College of Rheumatology (ACR) criteria were developed to classify patients diagnosed with SLE for research studies, not for clinical use1

Four of 11 criteria must be met at any time in the patients history

Additional symptoms indicating SLE may be evident upon presentation1

Symptoms Are Highly Varied

ACR SLE Classification Criteria1Some Additional Clinical

Features of SLE

Cutaneous Malar rash Discoid rash Photosensitivity Oral ulcers

Musculoskeletal Arthritis without deformed joints

Cardiopulmonary Pleuritis or pericarditis (inflammation of lining of the chest cavity

or heart)

Renal Proteinuria or cellular casts (excess protein or cells in urine)

Neurologic Seizures or psychosis

Hematologic Hemolytic anemia, leukopenia, lymphopenia, or thrombocytopenia

(decreased red blood cells, white blood cells, or platelets)

Immunologic Antibodies to native DNA, Smith antigen (Sm), or phospholipid Antinuclear antibodies (ANA)

Fatigue1,2

Unexplained fever1

Myositis2 (muscle weakness)

Alopecia1,2 (hair loss)

Raynaud phenomenon1,2

(pale or purple fingers and toes)

Vasculitis1,2 (inflamed blood vessels)

Nausea, vomiting1

Peripheral neuropathy1

Sicca complex2 (dry mouth or eyes)

Headache2,3

Psychiatric disorders (eg, depression, anxiety)3

6

Similarity and Overlap Between SLE Manifestations and Multiple Other Conditions1,2

SLE Manifestation1 Other Condition

Lupus arthritisFibromyalgia with positive ANA;

rheumatoid arthritis3,4

Thrombocytopenia Idiopathic thrombocytopenic purpura5

Positive ANA Antiphospholipid antibody syndrome2,6

Serositis Undifferentiated connective tissue disease7,8

Malar rash Rosacea; polymorphous light eruptions9,10

1. ACR Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 1999;42:1785-1796. 2. Cervera R, et al. Arthritis Rheum. 2002;46(4):1019-1027.

3. Calvo-Alen J, et al. Arthritis Rheum. 1995;38(10):1475-1484. 4. Levin RW, et al. Scand J Rheumatol. 1996;25(5):277-281. 5. John ML, Scharrer I. Hamostaseologie. 2012;32

Suppl 1:S86-S89. 6. Narain S, et al. Arch Intern Med. 2004;164:2435-2441. 7. Williams HJ, et al. J Rheumatol. 1999;26(4):816-825. 8. Bodolay E, et al. Clin Exp Rheumatol.

2003;21(3):313-320. 9. Black AA, et al. Lupus. 1992;1:229-237. 10. Pincus LB, et al. J Cutan Pathol. 2010;37:416-425.

Malar Rash Rosacea

Reproduced with permission courtesy of the National Rosacea Society

7

2013 American College of Rheumatology. Used with permission.

Variability in Symptoms at Presentation and Over Time Can Result in Difficulty in Diagnosis

Accurate diagnosis may take several years1

SLE may co-present with other autoimmune diseases2

Patients with SLE may present with different symptoms at different times3

No single test is sufficient to establish diagnosis4

SLE should be suspected in patients with manifestations in 2 organ systems

1. Hopkinson ND, et al. Ann Rheum Dis. 1994;53(10):675-680. 2. McDonagh JE, Isenberg DA. Ann Rheum Dis 2000;59:230-232. 3. Heinlen LD, et al. Arthritis Rheum.

2007;56:2344-2351. 4. ACR Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis Rheum. 1999;42:1785-1796. 5. Narain S, et al. Arch Intern Med.

2004;164:2435-2441.

In a study of 263 patients with presumptive SLE who were referred to an autoimmune disease center, 48% were ultimately diagnosed with a

different disorder5

8

9

Patient Case Study: Clinical Perspective*

Presentation

Patient presented with edema of ankles, fatigue

Patient reports joint pain, cold hands and feet, fever

Joint pain follow-up visit. X-ray indicates no erosion or subluxation. Patient reports all symptoms resolved

Rash on cheeks and nose

Dermatologist report

Patient presented with severe abdominal pain; reports occasional fever

Gastroenterologist report

Patient presented with severe Raynaud phenomenon

*Patient case study is for educational purposes only and represents hypothetical patient.

Denise G., 26-year-old African American female

Jun 11, 2010

Dec 20, 2010

Jan 20, 2011

Aug 22, 2011

Feb 1, 2012

Feb 7, 2012

Jul 16, 2012

Aug 15, 2011

Aug 9, 2012

Apparent effect from recent flight; advised to sleep with legs elevated

Flu test negative. Referred for x-ray of painful joints. Scheduled follow-up visit

Patient advised to make an appointment if symptoms return

Referred to dermatologist

Diagnosed with rosacea

Referred to gastroenterologist

Symptoms resolved prior to visit without intervention, possible inflammatory bowel disease

Referred to rheumatologist

Next Steps/Follow-UpDate

Rheumatologist report SLE diagnosis

9

Presentation

Patient presented with edema of ankles, fatigue

Patient reports joint pain, cold hands and feet, fever

Joint pain follow-up visit. X-ray indicates no erosion or subluxation. Patient reports all symptoms resolved

Rash on cheeks and nose

Dermatologist report

Patient presented with severe abdominal pain; reports occasional fever

Gastroenterologist report

Patient presented with severe Raynaud phenomenon

Denise G., 26-year-old African American female

Jun 11, 2010

Dec 20, 2010

Jan 20, 2011

Aug 22, 2011

Feb 1, 2012

Feb 7, 2012

Jul 16, 2012

Aug 15, 2011

Aug 9, 2012

Apparent effect from recent flight; advised to sleep with legs elevated

Flu test negative. Referred for x-ray of painful joints. Scheduled follow-up visit

Patient advised to make an appointment if symptoms return

Referred to dermatologist

Diagnosed with rosacea

Referred to gastroenterologist

Symptoms resolved prior to visit without intervention, possible inflammatory bowel disease

Referred to rheumatologist

Next Steps/Follow-UpDate

Rheumatologist report SLE diagnosisAug 9, 2012 Rheumatologist report SLE diagnosis

Jun 11, 2010

Patient Case Study: Clinical Perspective*

*Patient case study is for educational purposes only and represents hypothetical patient.

Denise G.: On the Path to Diagnosis

10

I felt so tired again today, even though yesterdayI was fine!

My fever keeps coming and going.

Why cant any of the doctors figure out whats wrong with me?

My friends are starting to think its all in my head, and sometimes I would wonder if theyre right

Why is this happening to me?

Patient perspective is for educational purposes only

and represents hypothetical patient.

2/1/2010

RS27960Sticky NoteMarked set by RS27960

Pathogenesis

UV light

Environmental Triggers

Immune Dysregulation

Multiple Factors Result in Systemic Immune Dysregulation Leading to SLE*

SLE

Sex Hormone InteractionsFemale predominance

Mok CC, Lau CS. J Clin Pathol. 2003;56(7):481-490.

Multiple Genetic Polymorphisms

12

*Etiology is unknown, but factors presented here are thought to have major roles.

13

Immune Dysregulation Has Multiple Consequences

Defective clearance mechanisms fail to remove cellular material exposed through normal apoptosis (cell death)1

Failure of normal immune checkpoints leads to loss of self-tolerance2

Abnormal immune cells treat the bodys own cellular components like foreign pathogens and produce autoantibodies1

1. Mok CC, et al. J Clin Pathol. 2003;56:481-490. 2. Tsokos GC. N Engl J Med. 2011;365:2110-2121.

14

Immune Dysregulation Has Multiple Consequences (cont)

SLE is characterized by pathologic production of antibodies directed against self-antigens1

Antinuclear antibodies are hallmark of disease

Abnormal activation of B and T cells

Autoantibodies form immune complexes with self-antigen that get deposited in tissue2,3

Defective clearance mechanisms allow complexes to persist2,3

Deposition of autoreactive B cells and immune complexes in tissues result in inflammation and can lead to organ damage2,3

Damaged tissue stimulates additional immune response and inflammation, creating a vicious cycle of immune overactivity2-4

1. Muoz LE, et al. Rheumatology (Oxford). 2005;44:1101-1107. 2. Mok CC, et al. J Clin Pathol. 2003;56:481-490. 3. Tsokos GC. N Engl J Med. 2011;365:2110-2121. 4. Crow MR. Arthritis Res Ther. 2009;11:245-256.

Numerous Factors Contribute to Underlying SLE

Pathogenesis and Subsequent Organ Damage1,2

Initiate Autoimmunity Immune Dysfunction

Inflammation and Organ/Tissue Damage

Genetic Susceptibility

(Immune-Related)

Stimuli(eg, Environmental,

Hormonal)

MusculoskeletalSystem

Brain

Heart

Lungs

Skin

Kidneys

Adaptive Immune System Activation

Immune Reactivity

Cytokines

Cytokines

Innate ImmuneSystem Activation

Autoantibodies

Cytokines

Autoimmune Amplification

1. Tsokos GC. N Engl J Med. 2011;365:2110-2121. 2. Mok CC, et al. J Clin Pathol. 2003;56:481-490. 3. Crow MR. Arthritis Res Ther. 2009;11:245-256. 15

Impact on Patients: Mortality and Morbidity

Bernatsky S, et al. Arthritis Rheum. 2006;54:2550-2557.

SLE Is a Chronic Disease With Higher Than Expected Mortality Rate

Collaboration of the Systemic Lupus International Collaborating Clinics (SLICC) and the Canadian Network for Improved Outcomes in Systemic Lupus (CaNIOS) investigator groups (US, Canada, England, Scotland, Iceland, Sweden, South Korea). Death data were prospectively collected or acquired through probabilistic linkage to vital statistics registries. Expected deaths in the general population were determined by multiplying person-years at risk in the cohort by the geographically appropriate age-, sex-, and calendar-year period-matched mortality rates. Risk of death was assessed as a standardized mortality ratio, calculated as the observed number of deaths divided by the number expected in the general population. Duration of disease at time of enrollment was

Compared to the general population,mortality rates were estimated to be1: ~8x higher from

renal causes

~5x higher from infections

~2x higher from heart disease

Organ damage is one of the most important correlates with mortality2

*Cause of death was acquired through probabilistic linkage to vital statistics registries. It is possible that the primary cause of death when identified as lupus was actually another

condition (eg, cardiovascular disease or infection), but the patients preexisting diagnosis of SLE may have led to this being listed as the cause of death.

1. Bernatsky S, et al. Arthritis Rheum. 2006;54:2550-2557. 2. Alarcon GS, et al. Arthritis Care Res. 2001(2);45:191-202.

23

109

53 2

Column1

Most Common Causes of Death1

(N=1255)*

Most Common Causes of Death in SLE Are Conditions Typically Associated With Aging1

Collaboration of the Systemic Lupus International Collaborating Clinics (SLICC) and the Canadian Network for Improved Outcomes in Systemic Lupus (CaNIOS) investigator groups (US, Canada, England, Scotland, Iceland, Sweden, South Korea). Mortality data were collected for 9547 patients followed 1958-2001 (76,948 person-years). A total of 1255 deaths occurred. Specific causes of death were not available from all cohorts. Duration of disease at time of enrollment was

Percentage of Patients With Permanent Organ Damage

*The SDI (SLICC/ACR Damage Index) is a widely accepted scale that measures irreversible changes present for at least 6 months attributable to lupus, concomitant diseases,

or treatment in 12 organ systems.

Chambers SA, et al. Rheumatology (Oxford). 2009;48:673-675.

One-Third of SLE Patients Accrue Permanent Organ Damage Within 5 Years of Diagnosis

10%

33%

51% 55%65%

100%

0

20

40

60

80

100

1 Year (N=232)

5 Years (N=232)

10 Years (N=232)

15 Years (N=143)

20 Years (N=75)

25 Years (N=6)

Pe

rce

nt

of

Pa

tie

nts

Wit

h S

DI*

1

5 Years(N=232)

1 Year(N=232)

10 Years(N=232)

15 Years(N=143)

20 Years(N=75)

25 Years(N=6)

0.11 0.42 0.77 1.01 1.26 2.17Mean

Damage Score

Retrospective analysis of records for patients with 10 years of consistent follow-up presenting at the University College London Hospital SLE clinic. Year 0 represents time of diagnosis. Mean age at diagnosis was 31.2 years, 95% of patients were female, 72% were white, 14% were black, 10% were Asian (Indian), and 4% were other.

19

0

10

20

30

40

50

60

0 1 2 3 4 5

Percentage of Patients With Organ Damage Over 5 Years of Follow-Up

(N=298)

Disease Activity Over 5 Years of Follow-Up (N=298)

Patients Still Accrue Organ Damage Even With Low/Moderate Disease Activity

0

2

4

6

8

0 1 2 3 4 5

*The SLEDAI-2K (SLE Disease Activity Index 2000) is a validated measure of global SLE disease activity.The SDI (SLICC/ACR Damage Index) is a validated measure of to assess damage in SLE.Urowitz MB, et al. Arthritis Care Res. 2012;64:132-137.

Me

an

To

tal S

LE

DA

I-2

K*

Years in Registry

Pe

rce

nt

of

Pa

tie

nts

Wit

h S

DI

>0

Years in Registry

Prospective analysis of patients in the SLICC cohort recruited within 15 months of diagnosis and followed annually for 5 years. Mean age at enrollment: 35.3 years; 87% female; 55% white, 12% black, 14% Asian, 16% Hispanic, 2% other. At enrollment, mean disease duration=5.5 months; mean SLEDAI-2K score=5.9.

20

Organ Damage May Be Subclinical inSLE Patients

Higher in SLE patients vs controls2,3

Prevalence of plaque in internal carotid artery is 3x higher

Inadequate blood-vessel dilation (endothelial dysfunction), a sign of early plaque formation, is twice as common

1. Houssiau FA, et al. Br J Rheumatol. 1998;37(4):448-453. 2. Ahmad Y, et al. Rheumatology. 2007;46:983988. 3. El-Magadmi M, et al. Circulation. 2004;110:399-404.

Subclinical Cardiovascular Disease

Patients and Their Clinicians May Be Unaware As Organ Damage Accrues

Osteonecrosis may be

asymptomatic in SLE

patients1

Bone Tissue Death

53% of Osteonecrotic Hips May Be Asymptomatic1

21

Cognitive Impairment*4Cardiovascular Disease1 Osteoporosis2 ESRD3

Organ Damage Can Result in Development of Chronic Diseases Usually Associated With Increased Age

22

ESRD =end-stage renal disease.

*Cognitive impairment involves dysfunction in the areas of complex attention, learning, memory, visual perception, and arithmetic. Impairment may involve specific domains or be global.

1. Esdaile JM, et al. Arthritis Rheum. 2001;44:2331-2337. 2. Ramsey-Goldman, et al. Arthritis Rheum. 1999;42(5):882-890. 3. Ward MM. Arch Intern Med. 1992;152(10):2082-2088.

4. Petri M, et al. J Rheumatol. 2008;35:17761781.

Esdaile JM, et al. Arthritis Rheum. 2001;44:2331-2337.

Risks for coronary heart disease (CHD) and stroke are estimated to be significantly higher than in the general population

Cardiovascular Disease Can Be an Ongoing Issue for Patients With SLE

Cardiovascular Disease

Risk for GeneralPublic

7.5x risk of CHD compared to age-matched

controls

7.9x risk of stroke

compared to age-matched controls

23

Incidence of Myocardial Infarction (MI) in Young, Premenopausal Women Is High

Manzi S, et al. Am J Epidemiol. 1997;145:408-415.

Prospective analysis of the incidence of MI in 498 women with SLE. Cardiovascular incidence rates were compared to 2208 women of similar age participating in the Framingham Offspring Study, a prospective investigation of cardiovascular disease in the children of the 5209 men and women who participated in the original Framingham Heart Study. A comparison of MI rates was made over the same time period (1980-1993).

Compared to the general population, rate of MI was higher in women with SLE overall

Rate of MI is more than50 times greater for women with SLE aged 35-44

Incidence of MI in Women by Age

0

1

2

3

4

5

6

7

8

9

15-24 25-34 35-44 45-54 55-64

General Population

SLE PatientsIn

cid

en

ce

Rate

of

MI

p

er

10

00

Pe

rso

n-Y

ea

rs

(n=2208)

(n=498)

24

Ramsey-Goldman, et al. Arthritis Rheum. 1999;42(5):882-890.

Fracture Risk

Risk for GeneralPublic

Estimated 5x more likely to have bone fracture compared

to age-matched controls

18- to 24-year-olds are estimated to be 12x more

likely to have bone fracture

Fracture risk is estimated to be significantly higher than in the general population

Osteoporosis Is a Major Concern for Patients With SLE

25

Nephritis* Impacts the Majority of Patients As SLE Progresses

Nephritis

Cumulative incidence of 54%1*

54%

Present in 34% of adult patients at time of diagnosis1*

34%

26

Prevalence is higher in African Americans and Hispanics than in

whites1; higher in men than in women2

Renal damage is one of the most important predictors of mortality

for patients with SLE3

ESRD=end-stage renal disease

*Lupus nephritis defined as (1) renal biopsy demonstrating WHO, class II-V histopathology; and/or (2) proteinuria 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the

following features also attributable to SLE and present on 2 or more visits, done at least 6 months apart: proteinuria 2+, serum creatinine 1.4mg/dl, creatinine clearance

79ml/min, 10 red blood cells or white blood cells per high power field (HPF), 3 granular or cellular casts per HPF. Patients in whom other diseases (such as diabetes) might have

explained abnormal urinary findings were excluded.Patients were followed for a mean of 5.5 years, and up to 8 years.

Renal damage ascertained using the SLICC Damage Index (SDI) at last visit.

1. Bastian HM, et al. Lupus. 2002;11:152-160. 2. Tan TC, et al. J Rheumatol. 2012;39(4):759-769. 3. Danila MI. Rheumatology. 2009;48:542-545.

Involvement of cerebral microvasculature may result in

diverse central nervous system syndromes6

Neuropsychiatric Syndromes Affect From 37% to 80% of SLE Patients1-5*

Most Common Manifestations1

Cognitive dysfunction7

Headache

Depression

Anxiety

Less Common Manifestations1

Seizures

Psychosis

Movement disorders

*Definition of neuropsychiatric lupus included headache, per American College of Rheumatology criteria. Not all manifestations observed in SLE patients may be attributed to SLE. Cognitive dysfunction included difficulties in attention, concentration, memory, and visual perception.

1. Brey RL, et al. Neurology. 2002;58:1214-1220. 2. Hanly JG, et al. J Rheumatol. 2004;31(11):2156-2162. 3. Sanna G, et al. J Rheumatol. 2003;30(5):985-992. 4. Mikdashi

J, Handwerger B. Rheumatology. 2004;43:1555-1560. 5. Hanly JG, et al. Ann Rheum Dis. 2010;69(3):529-535. 6. Brooks WM, et al. Arthritis Rheum. 2010;62(7):2055-2063.

7. Kajs-Wyllie M. J Neurosci Nurs. 2002;34(4):176-183. 27

Patient Case Study: Clinical Perspective*

Patient presents with edema of ankles, hands, eye area; reports increased fatigue and need to urinate at night. Lab tests reveal proteinuria with hematuria and cellular casts

*Patient case study is for educational purposes only and represents hypothetical patient.

Cheryl M., 38-year-old white female

Patient scheduled for renal biopsyApr 18, 2008

Mar 16, 2009

June 22, 2010

Nov 18, 2009

Apr 28, 2008

July 15, 2010

Sept 24, 2010

Renal biopsy report

Annual physical exam Lab tests indicate hypertension, hyperlipidemia, and insulin resistance

Painful frequent urination Urinary tract infection confirmed

Broken wrist from minor fall. Referred for DEXA scan

Results reveal patient hasosteopenia

Continued edema, fatigue, headaches. Urine is foamy

Lab tests reveal proteinuria with hematuria, cellular casts, elevated serum creatinine. Renal biopsy indicates class V membranous lupus nephritis

Follow-up appointment: persistent proteinuria with hematuria, cellular casts, elevated serum creatinine. Urine is brown. Patient reports numbness in extremities, frequent vomiting

Diagnosed with end stage renal disease, placed on dialysis, added to kidney transplant list

38-year-old white female, diagnosed with SLE in 1998

Presentation Next Steps/Follow-UpDate

28

Renal biopsy indicates class III focal lupus nephritis

Patient presents with edema of ankles, hands, eye area; reports increased fatigue and need to urinate at night. Lab tests reveal proteinuria with hematuria and cellular casts

Cheryl M., 38-year-old white female

Patient scheduled for renal biopsyApr 18, 2008

Mar 16, 2009

June 22, 2010

Nov 18, 2009

Apr 28, 2008

July 15, 2010

Sept 24, 2010

Renal biopsy report

Annual physical exam Lab tests indicate hypertension, hyperlipidemia, and insulin resistance

Painful frequent urination Urinary tract infection confirmed

Broken wrist from minor fall. Referred for DEXA scan

Results reveal patient hasosteopenia

Continued edema, fatigue, headaches. Urine is foamy

Lab tests reveal proteinuria with hematuria, cellular casts, elevated serum creatinine. Renal biopsy indicates class V membranous lupus nephritis

Follow-up appointment: persistent proteinuria with hematuria, cellular casts, elevated serum creatinine. Urine is brown. Patient reports numbness in extremities, frequent vomiting

Diagnosed with end stage renal disease, placed on dialysis, added to kidney transplant list

38-year-old white female, diagnosed with SLE 1998

Presentation Next Steps/Follow-UpDate38-year-old white female, diagnosed with SLE in 1998

Diagnosed with end-stage renal disease, placed on dialysis, added to kidney transplant list

28

Sept 24, 2010

Renal biopsy indicates class III focal lupus nephritis

*Patient case study is for educational purposes only and represents hypothetical patient.

Patient Case Study: Clinical Perspective*

This is supposed

to be the prime of

my life, but some

mornings I wake

up feeling like Im

80 years old. I feel

so weak since the

last renal biopsy,

Patient perspective is for educational purposes only and represents hypothetical patient.

and today I began

writing my will.

This is not where

I expected to be

at age 38!

29

7/29/2010

Cheryl M.: Facing End-Stage Renal Disease

The Burden of Lupus

In a telephone survey of 829 patients with SLE:

Nearly all patients (91%) had 1 valued life activity affected by SLE

Almost half (49%) were unable to perform 1 valued life activity

Patients With SLE Have Impaired Function Affecting Multiple Aspects of Daily Life

Katz P, et al. Arthritis Rheum. 2008;59:465-473.

42% 44%50%

58% 61%73% 74%

83%

0

20

40

60

80

100

Pe

rce

nt

of

Pa

tie

nts

Some of the Valued Life Activities Affected by SLE (N=829)

Prospective phone interview study of patients participating in the University of California at San Francisco Lupus Outcomes Studies. Valued life activity (VLA) disability was assessed using a scale rating the difficulty of performing 21 activities. Changes in VLA disability were assessed for 1 year from baseline. Affected VLAs were those with any level of difficulty or inability to perform. Mean age at baseline was 47.2 years, mean duration of SLE was 12.7 years, 91% were women, and 70% were white.

31

SLE Can Make the Demands of Everyday Life More Challenging

Multiple symptoms can make simple tasks seem impossible

Fatigue

Skin manifestations

Joint stiffness

Pain

Depression

Cognitive dysfunction

National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. Lupus: A patient care guide for nurses and other health

professionals.3rd ed. 2006. http://www.niams.nih.gov/Health_Info/Lupus/Lupus_Guide/chapter_1.asp#chp1_tre. Accessed May 8, 2013. 32

Fatigue Is One of the Most Prevalent Clinical Manifestations of SLE

88.7 85.5 82.6

0

10

20

30

40

50

60

70

80

90

100

Caucasian African American Hispanic

Zonana-Nacach A, et al. Lupus. 2000;9:101-109.

Pre

va

len

ce

of

Fa

tig

ue

(%

)

Prevalence of Fatigue Across Ethnic

Groups (N=223)

LUMINA=LUpus in MInorities: NAture Versus Nurture.

A subanalysis of 223 patients participating in LUMINA, a prospective, multiethnic study of the outcome of SLE patients diagnosed 5 years prior to study entry, conducted jointly by the University of Alabama at Birmingham, the University of Texas-Houston Health Science Center, and the University of Texas Medical Branch at Galveston.

Fatigue is prevalent across caucasians, African Americans, and Hispanics

Severity may be related to psychosocial factors and/or disease activity

33

(n=71) (n=83) (n=69)

Skin Manifestations and Photosensitivity Limit Activities of Daily Life

Cutaneous lupus with photosensitivity is associated with significant impairments related to symptoms, emotions, daily functioning, and overall quality of life1

Photosensitivity was self-reported in 68% of patients with cutaneous lupus1

Disease activity may be triggered by fluorescent lights as well as sunlight2

May cause patients to avoid outdoor activities1,3

1. Foering K, et al. J Am Acad Dermatol. 2012;66(2):220-228. 2. Rihner M, McGrath H Jr. Arthritis Rheum. 1992;35:949-952. 3. Wysenbeek AJ, et al. Ann Rheum Dis.

1989;48(6):461-463. 34

Survey: Work Loss Is a Common Consequence of SLE

Results from the National Burden of Lupus Survey, conducted by Gfk Roper Public Affairs and Communications from July through September 2011. Survey was designed to evaluate the daily and long-term impact of lupus on health, family relationships, career, and quality of life, and to identify potential gaps in communication. Includes feedback from 957 people in the lupus community (502 people with SLE [75% female], 204 supporters, 251 rheumatologists who treat SLE). Funded and developed by GlaxoSmithKline.

*To some extent.

Gfk Custom Research North America. National Burden of Disease Survey. 2011.

Only 31% of patients reported being employed

full time

63% quit work and/or retired earlier than

planned

67% reported reducing the

number of hours worked

83% said that having to leave their job was devastating*

84% said that not working

makes them feel inadequate*

35

SLE Increases Pregnancy Risks

SLE increases several risks to mother and child1,2

Risk of neonatal death is 7x greater than for the general population; risk of fetal death is 5x greater2

Yet the majority of women with SLE can have successful pregnancies1

Conceiving when lupus has been in remission 6 months significantly reduces risks3

Pregnancy loss has dropped from 43% (1960-1965) to 17% (2000-2003)4

1. Clowse MEB, et al. Am J Obstet Gynecol. 2008;199(2):127.e1-127.e6. 2. Yasmeen S, et al. J Matern Fetal Med. 2001 Apr;10(2):91-96. 3. Kwok LW, et al. Lupus. 2011;20:829-

836. 4. Clark CA. J Rheumatol. 2005;32(9):1709-1712. 36

Maternal Risks Fetal Risks

Preeclampsia1 Intrauterine growth restriction1

Thrombosis1 Preterm delivery2

Maternal mortality1 Neonatal/fetal death2

Pregnancy Risks May Lead Some Women to

Avoid Having Children

Concerns include1

Maternal/fetal risks

Medication teratogenicity

Fear of genetic transmission of

lupus to children*

Inability to care for child due to

disability or premature death

*SLE has a complex pattern of inheritance, involving multiple susceptibility genes. Both genetic and environmental factors play a role in the development of SLE, and transmission

cannot be predicted. Patient concerns about genetic transfer may be exaggerated.1,2

1. Clowse ME, et al. Arthritis Care Res. 2012;64:668-674. 2. Kelly JA, et al. Genes Immun. 2002;3(Suppl 1):S71-S85.

The majority of women with SLE

(>60%) have fewer biologic children than desired before

diagnosis, primarily by choice1

37

80% reported that lupus negatively impacted their ability to fulfill various family roles2

Mother/father

Husband/wife

Breadwinner

88% reported that poor mental health impaired their ability to participate in activities they found enjoyable2

*To some extent.1. Boomsma MM, et al. Arthritis Rheum. 2002;47:196-201. 2. Hassett AL, et al. Arthritis Care Res (Hoboken). 2012;64(9):1341-1348. 3. Gfk Custom Research North America. National Burden of Disease Survey. 2011.

SLE Impacts Psychosocial Well-Being and Interpersonal Relationships1

Depression is common and some patients are suicidal1

68%88%

68% said lupus affects virtually

every relationship they have3*

88% reported mental health and well-being of their entire family was affected by lupus2

38

Survey: Invisible Symptoms Create a Disconnect Between Patients and Those Around Them

Results from the National Burden of Lupus Survey, conducted by Gfk Roper Public Affairs and Communications from July through September 2011. Survey was designed to evaluate the daily and long-term impact of lupus on health, family relationships, career, and quality of life, and to identify potential gaps in communication. Includes feedback from 957 people in the lupus community (502 people with SLE [75% female], 204 supporters, 251 rheumatologists who treat SLE). Funded and developed by GlaxoSmithKline.

87% of patients say they

downplay symptoms to

avoid upsetting their families*

87%DownplaySymptoms

75% of patients say their family and

friends think they can do more than

they actually can*; think they can

improve their condition by eating

better or exercising more (80%)*;

and believe they can identify with

living with lupus (67%)*

MostFeel

Misunderstood

ManyFeel

Unsupported

Only 52% of patients say their family and friends are

very supportive; 78% of supporters describe

themselves as very supportive

39*To some extent.

Gfk Custom Research North America. National Burden of Disease Survey. 2011.

Denise G.: Living With SLE

40

My coworkers dont understand how it feels to be this tired. They resent that Im less productive.

I stopped making plans with friends because I never

know what tomorrow will bring. They take it personally. They dont realize how real my symptoms are.

Im starting to feel so alone.

Patient perspective is for educational purposes only

and represents hypothetical patient.

11/14/2012

Patient Support

Survey: Communication Gaps Exist Between Patients and Caregivers

Results from the National Burden of Lupus Survey, conducted by Gfk Roper Public Affairs and Communications from July through September 2011. Survey was designed to evaluate the daily and long-term impact of lupus on health, family relationships, career, and quality of life, and to identify potential gaps in communication. Includes feedback from 957 people in the lupus community (502 people with SLE [75% female], 204 supporters, 251 rheumatologists who treat SLE). Funded and developed by GlaxoSmithKline.

42

52% of patients with lupus report they

minimize their symptoms when they talk to their

physicians*

72% of physicians are unaware that patients

tend to under-report

their symptoms*

*To some extent.

Gfk Custom Research North America. National Burden of Disease Survey. 2011.

87% of patients wish there were more resources available to them*

43

Survey: Patients May Feel Less Supported Than Their Doctors Realize

Results from the National Burden of Lupus Survey, conducted by Gfk Roper Public Affairs and Communications from July through September 2011. Survey was designed to evaluate the daily and long-term impact of lupus on health, family relationships, career, and quality of life, and to identify potential gaps in communication. Includes feedback from 957 people in the lupus community (502 people with SLE [75% female], 204 supporters, 251 rheumatologists who treat SLE). Funded and developed by GlaxoSmithKline.

54% of doctors

are frustrated by the limited

resources available to

educate their patients*

*To some extent.

Gfk Custom Research North America. National Burden of Disease Survey. 2011.

Patient Counseling May Improve Quality of Life for Those With SLE1

Unpredictable nature of SLE had the greatest impact on emotional distress and quality of life2*

Frequency of flare was associated with depression and anxiety3

Increased education and perception of control over the illness were associated with reduced depression and anxiety regarding SLE challenges3

Environmental triggers, such as exposure to ultraviolet light, may be modified to limit onset and severity of flares4

1. Karlson EW, et al. Arthritis Rheum. 2004;50(6):1832-1841. 2. Gfk Custom Research North America. National Burden of Disease Survey. 2011. 3. Beckerman NL, et al. J Multidiscip Healthc. 2011;4:63-72. 4. National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. Lupus: A patient care guide for nurses and other health professionals. 3rd ed. 2006. http://www.niams.nih.gov/Health_Info/Lupus/Lupus_Guide/chapter_1.asp#chp1_tre. Accessed May 8, 2013. 44

*To some extent.

Patient Interactions Are Opportunities to Provide Support

Foster open communication1

Ask how patients are coping1

Changes in physical appearance

Limitations on daily function

Emotional state

Socioeconomic challenges

Emphasize participation in patient

support groups and other resources1

Provide patient education1

1. Beckerman NL, et al. J Multidiscip Healthc. 2011:63-72. 2. National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. Lupus:

A patient care guide for nurses and other health professionals. 3rd ed. 2006. ttp://www.niams.nih.gov/Health_Info/Lupus/Lupus_Guide/chapter_1.asp#chp1_tre.

Accessed May 8, 2013. 45

Remind patients to schedule regular preventive care visits2

Primary care, gynecologist, dentist, optometrist

Empower Patients to Take Charge of the Factors They Can Control

Diet1

Eat a balanced diet to minimize cardiovascular risk and inflammation,

maintain bone health, and prevent anemia

Exercise1

As tolerated, for physical/mental health and reduced fatigue

Sunscreen1

Protect against both UVA and UVB rays, fluorescent lights

Broad-spectrum protection sunscreen with minimum SPF 15

Sleep1

8-10 hours a night to combat fatigue; naps whenever needed

Reinforce that need for rest is not laziness

Stress1-3

Practice stress management techniques

Smoking1

Emphasize the importance of not smoking

Immunizations1,4

Human papillomavirus; influenza and pneumococcal, with killed vaccines

1. National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. Lupus: A patient care guide for nurses and other health professionals. 3rd ed. 2006.

http://www.niams.nih.gov/Health_Info/Lupus/Lupus_Guide/chapter_1.asp#chp1_tre. Accessed May 8, 2013. 2. Greco CM, et al. Arthritis Rheum. 2004;51(4):625-634. 3. Da Costa D,

et al. Arthritis Care Res. 1999;12(2):112-119. 4. van Assen S, et al. Ann Rheum Dis. 2011;70:414-422. 46

Focus on the Positive

Results from the National Burden of Lupus Survey, conducted by Gfk Roper Public Affairs and Communications from July through September 2011. Survey was designed to evaluate the daily and long-term impact of lupus on health, family relationships, career, and quality of life, and to identify potential gaps in communication. Includes feedback from 957 people in the lupus community (502 people with SLE [75% female], 204 supporters, 251 rheumatologists who treat SLE). Funded and developed by GlaxoSmithKline.

More than half (56%) of people

with lupus reported feeling

hopeful or optimistic, regardless of lupus*

56%Feel

Hopeful

Living with lupus affects my life, but

does not define me as a person:

87%*

87%Dont Let Lupus

Define Them

My healthcare professional is the best there

is when it comes to managing my lupus:

82%*

82%Trust HCPWith Care

Positive Outlook

47*To some extent.

Gfk Custom Research North America. National Burden of Disease Survey. 2011.

I was so achy today, but I pushed myself to put on sunblock and go for a 20-minute walk because I promised Nurse Samuels I would.

I am so glad I did! It gave me energy.

The fresh air really reminded me to

take things one day at a time and appreciate everything I have.

Its strange, but in some ways, lupus has been a wake-up call.

Its caused me to slow down and realize what is truly important in life.

Patient perspective is for educational purposes only

and represents hypothetical patient.

48

3/25/2012

Denise G.: Facing SLE With a Positive Outlook

Key Takeaways

Key Takeaways

SLE is an autoimmune disease with a range of

manifestations and variable course, which make

diagnosis a challenge

502013 GlaxoSmithKline group of companies. All rights reserved.

Produced in USA. BN2280R0 May 2013

Key Takeaways

SLE is an autoimmune disease with a range of

manifestations and variable course, which make

diagnosis a challenge

The pathogenesis of SLE involves immune dysfunction

leading to autoantibody production, inflammation, and

organ/tissue damage

502013 GlaxoSmithKline group of companies. All rights reserved.

Produced in USA. BN2280R0 May 2013

Key Takeaways

SLE is an autoimmune disease with a range of

manifestations and variable course, which make

diagnosis a challenge

The pathogenesis of SLE involves immune dysfunction

leading to autoantibody production, inflammation, and

organ/tissue damage

Immune dysfunction and subsequent organ/tissue

damage leave patients with SLE at risk for serious

chronic conditions and premature mortality

502013 GlaxoSmithKline group of companies. All rights reserved.

Produced in USA. BN2280R0 May 2013

Key Takeaways

SLE is an autoimmune disease with a range of

manifestations and variable course, which make

diagnosis a challenge

The pathogenesis of SLE involves immune dysfunction

leading to autoantibody production, inflammation, and

organ/tissue damage

Immune dysfunction and subsequent organ/tissue

damage leave patients with SLE at risk for serious

chronic conditions and premature mortality

SLE has a significant impact on daily function, work loss,

interpersonal relationships, and emotional health

502013 GlaxoSmithKline group of companies. All rights reserved.

Produced in USA. BN2280R0 May 2013

Key Takeaways

SLE is an autoimmune disease with a range of

manifestations and variable course, which make

diagnosis a challenge

The pathogenesis of SLE involves immune dysfunction

leading to autoantibody production, inflammation, and

organ/tissue damage

Immune dysfunction and subsequent organ/tissue

damage leave patients with SLE at risk for serious

chronic conditions and premature mortality

SLE has a significant impact on daily function, work loss,

interpersonal relationships, and emotional health

Patient education and empowerment are valuable tools for improving quality of life

502013 GlaxoSmithKline group of companies. All rights reserved.

Produced in USA. BN2280R0 May 2013

Thank You!