Daniel J. Wallace, MD, FACP, MACR - PowerPoint Presentation

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2. Daniel J. Wallace, MD, FACP, MACRAssociate Director, Rheumatology Fellowship ProgramBoard of Governors, Cedars-Sinai Medical CenterProfessor of Medicine, Cedars-Sinai Medical CenterDavid Geffen School of Medicine Center at UCLAIn affiliation with Attune Health

3. Learning ObjectivesApply the ACR diagnostic criteria to recognize patients who may have SLEUtilize and interpret laboratory findings to investigate possible SLEDevelop SLE treatment plans based on individual patients’ disease characteristics, treatment goals, and consensus recommendationsIdentify a validated SLE disease activity measure for regular patient monitoring

4. What Is Systemic Lupus Erythematosus?Systemic lupus erythematosus (SLE) is a progressive chronic autoimmune disease that results in inflammation and tissue damageCharacterized by flares, spontaneous remission, and relapsesHighly heterogeneousCan affect any part of the bodyOften damages skin, joints, heart, kidneys, lungs, nervous system

5. What Are Some Characteristics of Patients with SLE♀♂85% are womenDECADE1st 2nd3rd4th 5th6th7th8th9th10thPREVALENCERatio peaks in reproductive years Half develop organ-threatening diseaseNonorgan-threateningOrgan-threateningSex, Race, and EthnicityPetri M. Best Pract Res Clin Rheumatol. 2002;16:847-858. Petri M. Systemic Lupus Erythematosus. In: Imboden JB, et al, eds. Current Rheumatology Diagnosis and Treatment. 2007. Uramoto KM, et al. Arthritis Rheum. 1999;42(1):46-50. Rees F, et al. Ann Rheum Dis. 2017;69:2006-2017. Izmirly PM, et al. Arthritis Rheum. 2017;69:2006-2017.

6. Primary Care PhysiciansLupus Care SpecialistSLE SuspectedEstablish DiagnosisAssess Activity and SeverityDevelop Treatment PlanModerate/Severe Disease ManagementRefractory/Serious Disease ManagementAnnual ConsultationMonitoringDisease ActivityTreatment ToxicitiesMild DiseaseReferral Disease ActivityComplicationDisease Activity Monitoring

7. ACR (1997) Revised Criteria for Classification of SLESkin CriteriaButterfly rashDiscoid rashSun sensitivity Oral ulcerationsSystemic CriteriaArthritisSerositisKidney disorderNeurological disorderLaboratory CriteriaBlood abnormalitiesPositive ANA blood testImmunologic disorderAntiphospholipid antibodies, lupus anticoagulant, anti-DNA, false-positive syphilis test, positive anti-Sm4 of 11 needed for a diagnosisHochberg MC. Arthritis Rheum. 1997;40:1725. Tan EM, et al. Arthritis Rheum. 1982;25(11):1271-1277.

8. Petri M, et al. Arthritis Rheum 2009;60:S338.SLICC Revision of the ACR Classification of SLE Renal biopsy ORClinical criteria (at least 1)Cutaneous: acute or subacute cutaneous lupus, chronic cutaneous lupus, nasal/oral ulcers, nonscarring alopeciaInflammatory synovitis in ≥2 joints or ≥2 tender joints with morning stiffness that are observedOrgans: renal (U Pr/Cr >0.5G or RBC casts), neurologic (seizures, psychosis, mononeuritis multiplex, myelitis, peripheral or cranial neuropathy, cerebritis), hematologic (hemolytic anemia, WBC<4000 x 1 or lymphs <1000 x 1, platelets <100K once)Laboratory (at least 1)ANA, anti ds DNA (2x reference range if ELISA), anti Sm, anticardiolipin Ab 2X normal, lupus anticoagulant, biologic false positive, anti beta-2 glycoprotein, low C3, C4 or CH50, direct Coombs without hemolytic anemiaTotal of 4 clinical/lab criteria need to be present94% sensitive, 92% specific, fewer misclassifications (P=0.0082). 716 scenarios.

9. Common Signs and Symptoms of LupusPainful or swollen joints and muscle painUnexplained feverRashes, most common in sun exposed areasChest pain upon deep breathingUnusual loss of hairRaynaud’s phenomenonSensitivity to the sunEdema in legs or around eyesMouth ulcersSwollen glandsExtreme fatigue

10. Incidence of Clinical and Laboratory Manifestations of SLEPleural or Pericardial EffusionAdenopathy

11. Mucocutaneous Features of SLEMalar (butterfly) rashDiscoid lupus (DLE)Mucosal ulcersAlopeciaSubacute cutaneous lupus (SCLE)Cutaneous vasculitisBullous lupusPanniculitis

12. Malar RashErythema (redness)Flat or raisedOver the malar eminences (cheek bones) and bridge of the nose Resembles a butterflySpares the nasolabial foldsDifferentiates from rosacea which has a similar appearancePhotosensitiveCan be transient(several days or weeks)

13. Discoid LupusCan occur as part of systemic lupus or exist in isolation without any other organ involvement10% of discoid lupus patients will develop SLECoin-shaped scaly plaquesPlaques expand to form lesions with depressed central scarring and increased skin pigment around the edgeCan occur anywhere on the body, cause hair loss in the scalp

14. Vascular FeaturesVasomotor instability; dysautonomiaRaynaud’s phenomenon

15. Musculoskeletal InvolvementMusculoskeletal symptomsArthralgiaCommon presenting symptom (>76%)Usually symmetric hand and knee jointsArthritisSwelling erythema, warmth less commonNo bone erosion or fixed deformitiesMyositisInflammatory tendonitisMyalgiaMusculoskeletal system organ damageTendon degenerationFixed deformitiesOsteoporosis

16. SerositisLining of heart, lungs, abdomenPleuritis is inflammation of the lining of the lungsPericarditis is inflammation of the lining of the heartSymptoms include pain in chest with deep breathing or when lying flatFluid may accumulate (effusion) causing increased shortness of breath

17. Blood AbnormalitiesAnemiaDecreased red blood cells due to immune destruction/hemolysisThrombocytopeniaPlatelets < 100kLymphopenia/neutropenia Decreased white blood cells < 4k, particularly lymphocytes < 1.5kExclude other reasons MedicationsBlood lossInfectionDooley MA. In: Wallace DJ, Hahn BH, eds. Dubois’ Lupus Erythematosus. 8th Ed. Philadelphia, PA: Elsevier; 2012: 526.

18. Differential Diagnosis of SLEAutoimmuneRheumatoid arthritis, scleroderma, myositis, vasculitis, spondyloarthropathies, inflammatory bowel disorder, Behçet's disease, sarcoidosis, Sjogren’s syndrome, thyroiditis, polymyalgia rheumatica, undifferentiated connective tissue diseaseInfectionsTuberculosis, Lyme, Bacterial endocarditis, HIV, CMV, EBVFibromyalgiaAllergiesNeurologic disorders (esp myasthenia gravis, multiple sclerosis)Malignancy (esp, lymphoproliferative disorders)Drug-induced lupusChlorpromazine, methyldopa, isoniazid, hydralazine, procainamide, quinidinePsychiatric disordersBipolar illness, malnutrition, substance abuseWallace DJ. The Lupus Book. New York, NY: Oxford University Press; 2012. Manson JJ, et al. Orphanet Journal of Rare Diseases.2006, 1:6, http://bestpractice.bmj.com/best-practice/monograph/103/diagnosis/differential.html.

19. DiagnosisNo single test can determine whether a person has lupus, but several laboratory tests may help make a diagnosisDiagnostic TestsAntinuclear antibody (ANA) testAutoantibodies: anti-DNA, anti-Sm, anti-RNP, anti-Ro (SSA), and anti-La (SSB)Anticardiolipin antibodyAntiphospholipid antibodySkin biopsyKidney biopsyU.S. Department of Health and Human Services. National Institutes of Health. National Institute of Arthritis and Musculoskeletal and Skin Diseases. NIH Publication No. 03-4178. http://www.niams.nih.gov/Health_Info/Lupus/lupus_ff.asp. Accessed January 2013.

20. Summary of Useful Tests in SLESpecialized testing limited to selected clinical circumstances1234Routine screening for all patientsReadily available and inexpensive testing for select patients Reflex panel testing to characterize nature of lupus involvementLEVEL

21. Summary of Useful Tests in SLESpecialized testing limited to selected clinical circumstances1234Routine screening for all patientsReadily available and inexpensive testing for select patients Reflex panel testing to characterize nature of lupus involvementCBCComprehensive metabolic profileUrinalysisMuscle enzymesAcute phase reactants(eg, CRP, ESR)Chest X-rayEKGANAC3 or C4 complementAnti-dsDNATotal cost under $500

22. Summary of Useful Tests in SLESpecialized testing limited to selected clinical circumstances1234Routine screening for all patientsReadily available and inexpensive testing for select patients Reflex panel testing to characterize nature of lupus involvementClotting tests (eg, PTT)2D echoMusculoskeletalX-rays/ultrasoundRheumatoid factorAnti-CCPBone densitometryRelatively inexpensive

23. Summary of Useful Tests in SLESpecialized testing limited to selected clinical circumstances1234Routine screening for all patientsReadily available and inexpensive testing for select patients Reflex panel testing to characterize nature of lupus involvementAnti-SmAnti RNPAnti SSA (Ro) and SSB (La)Extractable nuclear antigensRPR (false positive syphilis serology)Lupus anticoagulantAnticardiolipin Other antiphospholipid antibodiesAntiphospholipid panel

24. Summary of Useful Tests in SLESpecialized testing limited to selected clinical circumstances1234Routine screening for all patientsReadily available and inexpensive testing for select patients Reflex panel testing to characterize nature of lupus involvementCT or MR imagingElectrical studies(eg, EEG, EMG)Bone scanNiche serologies (eg, Coombs, anti-histone, myositis panel)

25. Case Study: Diagnosing SLEKelsey, a 23-year-old Caucasian woman Unremarkable history until 3 months agoCurrently feels tired and achy, flu-like symptoms, heavier than usual periodsPhysical examSome fullness at MCP jointDull discomfort on taking deep breathsMild erythematous rash on cheeksMild erythema on forearmsSocialUnder stress at work, poor sleep, lack of exercise

26. Case Study: Laboratory FindingsNormal blood chemistry panelMild anemia (Hb = 11.0 g/dL) Ferritin = 8 ng/mLUrine: trace proteinuria, no casts or red cellsANA screen: notable for a 1:160 speckled patternSed rate = 30 mm/hrCRP 1.5 mg/L (normal < 1.0 mg/L)

27. Case Study: Work-UpSerologyRheumatoid factor: 25 (normal <20)Anti-CCP: negativeC3 complement: 68 (normal ≥ 70)C4 complement: 13 (normal ≥ 14)Anti-Sm, RNP, SSA, SSB, and anti-dsDNA: negativeChest X-ray: small right pleural effusionUrine protein/creatinine ratio: essentially negative

28. Kelsey’s SLE Diagnosis

29. Primary Care PhysiciansLupus Care SpecialistSLE SuspectedEstablish DiagnosisAssess Activity and SeverityDevelop Treatment PlanDisease Activity MonitoringModerate/Severe Disease ManagementRefractory/Serious Disease ManagementAnnual ConsultationMonitoringDisease ActivityTreatment ToxicitiesMild DiseaseReferral Disease ActivityComplication

30. Commonly Used SLE MedicationsMaidhof W, et al. P T. 2012 Apr; 37(4): 240-246.Inflammation, pain, feverT-cell, cytokinesInflammationT- and B-cellsB-cell survival and development

31. Currently Available OptionsPhysical Measures (All Patients)Establish DiagnosisDetermine Likely PrognosisAssess Severity and Organ InvolvementNo Major Organ InvolvementMajor Organ Involvement

32. AntimalarialsLow-dose steroidsAzathioprine/methotrexateCurrently Available OptionsPhysical Measures (All Patients)Establish DiagnosisDetermine Likely PrognosisAssess Severity and Organ InvolvementNo Major Organ InvolvementMajor Organ Involvement

33. Management of Nonorgan-Threatening LupusPhysical measures(eg, sun avoidance, exercise, splinting)MedicationCounselingSurgery (eg, biopsy)

34. Physical MeasuresSun avoidance, use of sunscreensTemperaturePhysical therapy (use of heat)Occupational therapyVocational rehabilitationExerciseDiet and vitaminsManagement of fatigue

35. Proactive and Preventive Strategies in SLEPatient education programsEliminate patient nonadherenceSpecialist accessExercise, PT, OT, ergonomic work stationsCognitive therapy (lupus fog), biofeedback (Raynaud’s)Aggressive vigilance for hypertension, hyperglycemia, hyperlipidemia, obesity, smoking cessationYearly bone densitometry and use of bisphosphonatesAnnual EKG, chest X-ray, duplex scanning, stress tests, 2-D echo for pulmonary pressures in high-risk patientsPrompt evaluation of all feversAntiphospholipid antibody screening and prophylaxis

36. Using NSAIDs for SLEFeversHeadacheArthralgias, myalgias, arthritisPleurisy, pericarditis

37. Treatment Algorithm (Partial)GC = systemic glucocorticoids HCQ = hydroxychloroquineIMM = immunomodulators MMF = mycophenolate mofetil AZA = azathioprine MTX = methotrexate RTX= rituximabBLM = belimumab CsA = cyclosporine ADLE = discoid lupus erythematosusIV CYC = intravenous cyclophosphamideOrgan Involvement1st Line or Induction2nd Line or Failure of Induction3rd LineConstitutional symptomsGC, HCQ, or combinationMMF, AZA, MTXSwitching to RTX or BLMWidespread DLEHCQ ± GCMMF, CsA, AZABLMUncomplicated digital/cutaneous vasculitisGC ± HCQ ± MTXAZA or MMFSwitching to IV CYCAdapted from: Muangchan C, et al. Arthritis Care Res (Hoboken). 2015;67(9):1237-1245.

38. Summary of Outcome Benefits and Disease-modifying Effects of Antimalarials in SLEHydroxychloroquineSustained benefit on overall survival, disease free survival, and damage accrualDelays the onset of SLE and reduces clinical flaresEarly use maximizes these benefitsProtective against thrombosis, even in APLA positive patientsAntimalarial class*Improve survival in time-dependent mannerAll 3 AMs have lipid-lowering properties which are apparent also in patients taking corticosteroidsBeneficial effect on glycemic status in SLE patients, and this benefit possibly increases with duration of useProtective effect against renal damage and major infections*Hydroxychloroquine, chloroquine, quinacrine; AM, antimalarial; APLA, antiphospholipid antibodies; HCQ, hydroxychloroquine

39. Using Antimalarials for LupusAfter 6-12 weeks, anti-inflammatory and sun protective80% response rate for nonorgan-threatening disease and cutaneous lupusDecreases flare rate and risk for organ disseminationAntiplatelet effects Lipid lowering effectsNo serious toxicity if appropriately monitoredCan be used in pregnancy and lactation

40. AAOS Recommendations on Screening for HCQ RetinopathyAt recommended doses (5.0 mg/kg real weight), the risk of toxicity… Up to 5 years  < 1% Up to 10 years  < 2% After 20 years  almost 20%ScreeningBaseline fundus exam to rule out preexisting maculopathyAnnual screening after 5 years for patients on acceptable doses and without major risk factorsPrimary screening tests Automated visual fields Spectral-domain optical coherence tomography (SD OCT)Retinopathy is not reversiblePatient education is crucialMarmor MF, et al; AAO. Ophthalmology. 2016;123(6):1386-1394.

41. HCQ TherapyEffective in early, mild diseaseAssociated with fewer thromboembolic eventsDecreases damage scores at 5 yearsBroder A, et al. J Rheumatol. 2013 Jan;40(1):30-3. Zheng ZH, et al. Lupus. 2012;21(10):1049-1056.Without HCQWith HCQP=0.003

42. Glucocorticoid TherapyMultiple agentsCortisol/hydrocortisone Prednisone/prednisolone Methylprednisolone Dexamethasone BetamethasoneWell-established benefitsAnti-inflammatory ImmunosuppressiveWell-established side effectsCV eventsDiabetes mellitus Osteoporosis, osteonecrosisInfectionsGlaucoma, cataractsPsychological disordersRuiz-Irastorza G, et al. Rheumatology (Oxford). 2012;51(7):1145-1153.

43. Corticosteroids and Immune SuppressionSuppress virtually every component of the immune responseWith chronic administration, expose patients to greater risk of viral and fungal infections

44. Steroid Use in Phase 3 TrialsPost-hoc analysis of 2 randomized trialsTrial designs allowed for steroid dose-adjustment based on patient’s disease activityPatients treated with belimumab had a smaller increase in cumulative corticosteroid dose because of greater decreases and smaller increases in doses*P<0.0001; **P=0.0165; †P=0.0005van Vollenhoven, et al. Arth Rheum. 2016;68:2184-2192***†

45. Effect of Prednisone on Organ DamagePrednisone Average Dose*Hazard Ratio> 0-6 mg/day1.16> 6-12 mg/day1.50>12-18 mg/day1.64> 18 mg/day2.51*Adjusting for confounding by indication due to SLE disease activityThamer M, et al. J Rheumatol. 2009;36:560–564.

46. Methotrexate (MTX)Most commonly prescribed RA DMARDNot FDA-approved for SLEUsed for moderate disease after HCQ failure/nontoleranceCommonly used for joint manifestations and as a steroid-sparing agentSakthiswary R, et al. Lupus. 2014;23(3):225-35.

47. Mycophenolate and AzathioprineMycophenolatePrimarily used for renal, or pulmonary involvementAzathioprineCan be used for renal, hematologic, musculoskeletal, dermatologic involvementCan be steroid sparing

48. Other Agents Used to Manage LupusSpecific agents for cutaneous subsetsRetinoids, antileprosy drugs, topical pimecrolimus or tacrolimusImmune thrombocytopenia (ITP)Danazol, intravenous immunoglobulin (IVIg), splenectomy, rituximabCNSIntrathecal methotrexate, cyclophosphamide, rituximabAntiphospholipid antibody syndrome (APS)Warfarin, heparin, platelet antagonistsRaynaud’sCalcium channel blockers, phosphodiesterase inhibitors, nitratesPulmonary hypertensionProstaglandins, phosphodiesterase inhibitors, endothelin blockers

49. Cyclophosphamide (IV)Mycophenolate mofetilCalcineurin inhibitors (cyclosporin A or tacrolimus)Biologics (eg, rituximab or belimumab) or Clinical trialCurrently Available OptionsPhysical Measures (All Patients)Establish DiagnosisDetermine Likely PrognosisAssess Severity and Organ InvolvementNo Major Organ InvolvementMajor Organ Involvement

50. Prevalence of Serious Organ- or Life-Threatening Complications With Idiopathic SLEPistiner M, et al. Semin Arthritis Rheum. 1991;21:55-64.ComplicationN%Nephritis12828Thrombocytopenia7316Cerebritis4911Thromboemboli368Hemolytic anemia348Seizures306Lupus pneumonitis, alveolar hemorrhage, or pulmonary hypertension296Avascular necrosis255ComplicationN%Psychosis245Organic brain syndrome225Lupoid hepatitis225Retinal vasculitis/infarct174Myocarditis123Mesenteric vasculitis41Thrombotic thrombocytopenic purpura41Total25254

51. Disease Activity Predicts Organ Damage and DeathA 1-point increase in adjusted BILAG score was associated with:8% increase in the risk of any new organ damage11% increase in risk of CV, pulmonary, or musculoskeletal damage15% increase in mortalityTime to SDI Δ ≥1 by Disease Activity Level* (N=350)Percent Survival020406080100024681012141620*Low disease activity=BILAG score 0 to <2.59; high disease activity=BILAG score ≥6.84 Length of Follow-up (years)SDI = Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index.Lopez R, et al. Rheumatology. 2012;51:491-498.

52. Clinical Features of Active Lupus NephritisUrine protein excretion—edemaActive urine sediment—WBCs, RBCs, protein casts, cellular castsDecreased glomerular filtration rateHypertensionDooley MA. In: Wallace DJ, Hahn BH, eds. Dubois’ Lupus Erythematosus. 8th Ed. Philadelphia, PA: Elsevier; 2013:438.

53. ACR Guidelines for Monitoring Activity of Lupus Nephritis1 Recommended Monitoring of Lupus Nephritis (monthly monitoring intervals)*BPUAProtein:CRSerum CRC3/C4 LevelsAnti-DNAActive nephritis at onset of treatment11112†3Previous active nephritis, none currently333336Pregnant with active GN at onset of treatment111111Pregnant with previous nephritis, none currently113333No prior or current nephritis366666*Values are the monthly intervals suggested as the minimum frequency at which the indicated laboratory tests should be measured in the SLE scenarios shown in the left-hand column. †Opinion of the authors based on a study published after the Task Force Panel had voted.2GN, glomerulonephritis; BP, blood pressure; UA, urinalysis; CR, creatinine.1. Hahn BH, et al. Arthrit Care Res. 2012;64:797-808.2. Grootscholten C, et al. Kidney Int. 2006;70:732-742.

54. Cardiac Manifestations of SLEPericarditisMyocarditis, congestive heart failureHypertensionCoronary vasculitisLibman-Sacks endocarditisValvular insufficiencySLE patients have a 7–10x increased risk of coronary heart disease and strokeEsdaile JM, et al. Arthritis Rheum. 2001;44:2331-2337.

55. Pulmonary Manifestations of SLEPleuritis (also pericarditis)Susceptibility to infectionLupus pneumonitis/alveolitisPulmonary hemorrhagePulmonary fibrosisShrinking lung syndromePulmonary embolism/in situ thrombosisPulmonary hypertensionQuadrelli SA, et al. Lupus. 2009;18:1053-1060.

56. Neuropsychiatric Manifestations of SLECentral nervous systemDiffuse cerebral manifestationsPsychiatric manifestations (depression)Cognitive impairmentSeizuresHeadacheFocal manifestationsPeripheral nervous systemFutrell N, et al. Neurology. 1992;42:1649-1657.

57. B-cell InhibitionRituximabOpen label trials suggested efficacy and safetyBoth major US trials failed but had faulty designEXPLORER (78-wk)1Patients with moderately-severely active, extrarenal SLERituximab + prednisone + AZA/MMF/MTXNo differences between rituximab and placebo in 1° or 2° endpoints“…aggressive background treatment and sensitive cutoffs for nonresponse.”LUNAR (52-wk)2Patients with class III/IV lupus nephritisRituximab vs placebo with background MMF and corticosteroidsNumeric difference (P=0.2) in response rate, and significant differences in several biomarkers“Rituximab…did not improve clinical outcomes after 1 year of treatment.”AZA =  azathioprine; MMF = Mycophenolate mofetil; MTX = Methotrexate1. Merrill JT, et al. Arthritis Rheum. 2010 ;62:222-33. 2. Rovin BH, et al. Arthritis Rheum. 2012;64:1215-1226.

58. When Is Rituximab Used?Central nervous system lupusUsually after steroids and cyclophosphamide have failedHematologic SLEIn the setting of idiopathic thrombocytopenia or hemolytic anemias where treatment with steroids and IVIG has failed Catastrophic antiphospholipid antibody syndromeWhen IV steroids, heparin, and plasma exchange or IVIG have failed Refractory inflammatory arthritisNone of these uses are FDA-approved

59. Belimumab Is a BLyS-Specific InhibitorIndicated for the treatment of adult patients with active, autoantibody-positive SLE who are receiving standard therapyOnly biologic approved for SLEFirst drug approved for SLE (2011) since 1957BENLYSTA [package insert]. Rockville, MD: Human Genome Sciences, Inc. 2011.

60. Belimumab Pivotal Trial (BLISS-52) Randomized controlled trial (N = 865)SeropositiveActive disease (SELENA-SLEDAI ≥6)Treatment (plus standard therapy)Belimumab 1 mg/kg (n=288) Belimumab 10 mg/kg (n=290) Placebo (n=287)Higher response rate at 52 weeks1 mg: 51% (P=0.013 vs placebo)10 mg: 58% (P=0.0006 vs placebo)Other treatment benefitsFewer symptoms and signs of disease activity (ie, lower SELENA-SLEDAI score)Fewer patients with very active disease or flares (ie, BILAG A or BILAG B) No worsening in global assessment scores (ie, PGA score)Similar rate of adverse events Navarra SV, et al; BLISS-52 Study Group. Lancet. 2011;377(9767):721-731.SLE Responder Index (1o Endpoint)

61. Long-term Safety and Efficacy StudyContinuation of phase 2 trial with 10 years of follow-upBelimumab 10 mg/kg every 4 weeks plus standard of care*Response measured with the SLE Responder Index (SRI); †Median percent change from baselineWallace DJ, et al. Ann Rheum Dis. 2017;76(S2):150Response to Belimumab Increased *Prednisone Use Decreased†

62. Currently Available OptionsPhysical Measures (All Patients)Establish DiagnosisDetermine Likely PrognosisAssess Severity and Organ InvolvementNo Major Organ InvolvementMajor Organ InvolvementLifestyle (sun avoidance, etc)Topical agentsSymptomatic agentsComorbid conditions

63. Case Study: Treatment for KelseyTherapy should begin with prednisone and HCQAlso consider NSAIDs Treat associated comorbidities (eg, heavy periods with iron-deficiency anemia)

64. Case Study: What Would Necessitate Escalating Therapy?Symptoms not resolvingKidney involvement Intolerable side effectsNonadherenceNew increase in anti-dsDNA antibodiesDecrease in C3 or C4 levelsNew increase in CRP and sed rate

65. Primary Care PhysiciansLupus Care SpecialistSLE SuspectedEstablish DiagnosisAssess Activity and SeverityDevelop Treatment PlanDisease Activity MonitoringModerate/Severe Disease ManagementRefractory/Serious Disease ManagementAnnual ConsultationMonitoringDisease ActivityTreatment Toxicities Disease ActivityComplicationMild DiseaseReferral

66. Case Study: Assessing KelseySigns/symptomsLabsAdherence“Have you been adherent?”“How many doses did you miss last month?”Are symptoms from Lupus?Medication?Lack of medication?Comorbidity?Lifestyle factor?

67. Medication Nonadherence is a ProblemUS Medicaid data from 2000-2006 Adults ages 18-64 years with SLE New users of HCQ (n = 9600) or ISMs (n = 3829)Outcomes All-cause and SLE-related ED visits Hospitalizations Nonadherence79% of HCQ users 83% of ISM usersFeldman CH, et al. Arthritis Care Res (Hoboken). 2015 Dec;67(12):1712-21.

68. Medication Nonadherence is a ProblemIncidence Rate Ratio for NonadherersED, emergency department; HCQ, hydroxychloroquine; IRR, incidence rate ratio; ISM, immunosuppressive medications Feldman CH, et al. Arthritis Care Res (Hoboken). 2015 Dec;67(12):1712-21.

69. Case Study: Monitoring KelseyScreen for organ-threatening diseasePatient education, disease monitoring, and adherence assessment should be reinforced in the next office visitsBenefits of educational sessions are documented in the literature Review benefits, side effects, and complications of NSAIDs, antimalarials, corticosteroids

70. Key PointsDiagnosis by rheumatology is the gold standardScreen early for organ-threatening diseaseEarly treatment NSAIDs should be consideredSteroids may be useful in early, active disease, if used with cautionPatients should receive an antimalarialAdherence is critical at all disease stagesPatient education, disease monitoring, and adherence assessmentEven mild disease should be overseen by a lupus care specialist at least annually or by phone consultationFlares happen and can be subtle