of 57 /57

SLE Discussion Topics - Talk SLE€¦ · SLE Discussion Topics •The Path to Diagnosis ... Aug 9, 2012 ––Rheumatologist Rheumatologist reportreport –SLE SLE diagnosisdiagnosis

  • Author
    lecong

  • View
    221

  • Download
    0

Embed Size (px)

Text of SLE Discussion Topics - Talk SLE€¦ · SLE Discussion Topics •The Path to Diagnosis ... Aug 9,...

  • 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!