Standard of care for RA in SA 2013

Transcription

1 Standard of care for RA in SA 2013

2 Background Rheumatoid arthritis (RA) is a chronic inflammatory disease, which if treated inadequately leads to irreversible joint damage, resulting in deformities, disability and premature mortality. The disease occurs worldwide and affects approximately 1% of the population

3 Severity (arbitrary units) RA Progression Early RA Intermediate Late Inflammation Disability Radiographs ACR Duration of Disease (years) Graph: Adapted from Kirwan JR. J Rheumatol 2001;28: Photo: Copyright American College of Rheumatology.

4 Early diagnosis of the disease Evidence for the benefit of early therapy Assessment of response to therapy with the development of composite disease activity Target-directed therapy where the target is remission Better understanding and use of medication Biologic disease modifying anti-rheumatic (DMARD) drugs

5 The process South African Rheumatism and Arthritis Association (SARAA) has proposed the development of an updated treatment strategy for the effective therapy of RA in South Africa Survey of rheumatologists Survey of the literature Development of a treatment algorithm

6 Key principles of treatment of RA Early diagnosis and treatment Assessment of disease activity and disability Radiography Treat to target Treatment of RA Traditional DMARDs The place of glucocorticoids NSAIDS Biologic DMARDs Complications of RA and safety issues

7 Early diagnosis and treatment

8 Early referral recommendations for potential RA Which symptoms/signs? Alarm signals 3 swollen joints MTP/MCP involvement (Squeeze Test positive) Morning stiffness 30 minutes Emery et al. 2002

9 2010 ACR /EULAR RA Classification criteria Joint involvement 0-5 points according to number of joints Serology 0-3 points for low or high positive ACPA, RF Acute phase reactants 0-1points for elevated CRP or ESR Duration of symptoms < or > 6 weeks 0-1 points 6 points = Definite RA

10 Assessing disease activity and disability Composite index of disease activity

11 Simplified Disease Activity Index: SDAI SDAI = Tender joint count (0-28) + Swollen joint count (0-28) + Patient Global* (0-10 cm) + Physician Global*(0-10 cm) + CRP (mg/dl) SDAI 40 Disease Activity Severe Moderate Improvement: Major: > 20 points Minor: points No: < 10 points *Assessment of Disease Activity, based on VAS 20 5 Low Remission Smolen JS, Breedveld FC, Emery P, et al. Rheumatology. 2003;42:

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13 Consequence of RA: Disability Work disability: 25% of patients at 6.4 years after disease onset 50% at 20.9 years 50% of patients will reach the following loss of function (measured by HAQ disability index): Moderate within 2 years (HAQ DI of 1) Severe within 6 years (HAQ DI of 2) Very severe within 10 years (HAQ DI of 2.5) Wolfe F, Cathey MA. J Rheumatol 1991;18: Wolfe F, Hawley DJ. J Rheumatol 1998;

14 Maximum Disability (%) Maximum Damage (%) Links Between Disability and Joint Damage Average Average Disease duration (years) Disease duration (years) Scott DL, et al. Rheumatology 2000;39:

15 Inflammation and structural damage are associated with work productivity Inflammatory Process Functional Disability Structural Damage Work productivity Presenteeism Employment status Absenteeism Work instability Van Vollenhoven RF, et al. Arthrit Care Res 2010;62:

16 5-Yr Costs/Patient (US $ x1000) After Disability Annual Costs as a Function of Disability * Hospitalization, surgery, loss of employment, long-term care. Pre-biologics era. Fries JF. Ann Rheum Dis 1999;58(Suppl 1):I86-I89. HAQ

17 Health Assessment Questionnaire Disability Index (HAQ-DI) 8 categories 20 questions Each ranges from 0 to 3 0 = no difficulty, 1 = some difficulty, 2 = much difficulty or with assistance, 3 = unable Score 2 for item that uses devices &/or another person HAQ score is average of worst score in each of 8 categories The total score ranges from 0 to 3 Buchbinder R et al. Arthritis Rheum. 1995;38: Sullivan FM et al. Ann Rheum Dis. 1987;46:

18 HAQ HAQ reversibility may differ by disease severity and duration Early intervention can lead to normal functionality among RA patients PREMIER (Early RA): Observed mean HAQ by baseline disease severity DE019 (Long-Standing RA): Observed mean HAQ by baseline disease severity Moderate disease RA population HAQ Normal population HAQ Baseline Weeks Severe disease RA population HAQ Normal population HAQ Baseline Weeks van Vollenhoven RF, et al. ACR 2009, Philadelphia

19 Prognostic factors High RF and Anti cyclic citrillunated protein antibody (ACPA) positive High CRP and ESR Functional limitation ( high HAQ) Extra-articular disease Bony erosions on X-ray early in disease Others -comorbid conditions -smoking -lack of education - low socioeconomic status

20 Other imaging in RA MRI High resolution ultrasound

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23 Serious and considerable comorbidities Osteoporosis Cardiovascular disease GIT NSAID induced gastropathy Eye involvement Lung disease

24 Osteoporosis Bone loss is an important consequence of longstanding RA Generalized osteoporosis Femur Lumbar spine The mechanism: Inflammation Immobilization Age Menopausal Glucocorticoid (GC) therapy Possibly dose as low as 2.5mg lower BMD threshold for intervention should be used Calcium and vitamin D supplementation

25 Cardiovascular disease in RA Study looking at the incidence of IHD: 49% in RA pts 27% in OA pts Up to 50% of deaths of RA patients due to CVD

26 Cardiovascular events Risk factors: Male sex Higher age at disease onset HLA-B27 High disease activity Corticosteroid treatment early in disease Hypertension Higher haptoglobin level High ESR and CRP Extra-articular manifestations of RA serositis cutaneous vasculitis Smoking Dyslipidaemia

27 Addressing cardiovascular risk in RA Assessment of cardiovascular risk Aggressive treatment of risk factors Hypertension Hypercholesterolaemia Treat to target of DM patients Treat the RA Lower incidence of IHD on MTX and TNF blockers

28 RA and HIV infection HIV infection can cause musculoskeletal syndromes mimicking RA HIV testing may be appropriate Treatment of the HIV positive patient with RA Information on the safety of using immunosuppressive drugs in an HIV positive patient is limited MTX and biologic DMARDs Not recommended Chloroquine of sulfasalazine: Safer Difficult to assess disease activity in HIV positive patients

29 Pregnancy RA tends to improve during pregnancy DMARDs are not recommended during pregnancy Stop 3 months before stopping contraception MTX is contra-indicated in pregnancy and breastfeeding Sulfasalazine and chloroquine safer MTX and sulphasalazine should be stopped for men wanting to father children Low dose GC are safe Biologic DMARDs No specific safety concern but little evidence Anti-TNF drugs, abatacept and tocilizumab: Stopped at conception Rituximab: Should not be given 12 months before conception

30 Treatment of RA: Non Pharmacologic Multidisciplinary approach Physical therapy Exercise Rest Splinting Joint protection Assistive devices

31 Pharmocologic treatment of RA Symptomatic Disease modifying (DMARDs)

32 Tight control: Aggressive treatment can halt the disease Treat to target Remission or low disease activity

33 Treat to target principals Treatment is a shared decision between Rheumatologist and patient Maximise quality of life through control of symptoms, prevention of structural damage, maintain function and social participation Abrogation of inflammation to achieve maximal QOL Treating to target by measuring disease activity and adjusting therapy optimises outcomes Early treatment increases chance of remission

34 Clinical remission: absence of signs and symptoms of clinical disease activity Residual disease activity is realistic in longstanding disease Targets must include low disease activity Until target is reached: therapy adjusted every 1-3 months Validated composite scores include joint counts and laboratory monitoring

35 Symptomatic treatment Analgesics Simple analgesics Use appropriately as needed Additional pain treatment

36 NSAIDs No disease modifying effect Ideally used as needed Side effects should not be under estimated Gastric Gastroprotection Cardiovascular All NSAIDs

37 The use of glucocorticoids Disease modifying effect in early disease Used to control disease while waiting for DMARDs to become effective Not appropriate as long term therapy Intra-articular use

38 The DMARDs Certolizumab pegol Golimumab modified from Klareskog L et al. Lancet 2009;373:

39 The synthetic DMARDs Methotrexate (MTX) is still drug of choice Start at 7,5 15mg/week Maximum 25mg per week Adverse events rare Sulphasalazine Chloroquine Leflunamide

40 Conventional treatment with DMARDs: Start ASAP MTX first line Give appropriate dose Sulphasalazine and chloroquine Combination with MTX Monotherapy Mild disease MTX intolerance Leflunamide Same effect and side effect profile as MTX Use in MTX intolerance Can be used in combination with MTX

41 The biologic DMARDs Why biologic DMARDs Disease control Inhibition of damage Because of the concerns about TB in SA: TNF inhibitors Non TNF inhibitors Efficacy is very similar Life changing therapy

42 TNF inhibitors: Infliximab (Revellex ) 3mg/kg dose every 6 8 weeks IVI Etanercept (Enbrel ) 50mg weekly sc Adalimumab (Humira ) 40mg every second week sc

43 The Non TNF inhibitors Rituximab (MabThera ) CD-20 positive B-cell depletion 1000mg x2, two weeks apart IVI Every 6 months Abatacept (Orencia ) Blocks co-stimulation of T-cells mg monthly IVI Tocilizumab (Actemra ) Il 6 inhibitor 8mg/kg dose monthly IVI

44 SARAA recommendations Criteria for the commencement of biologic therapy 6-month trial of at least 3 synthetic DMARDs (including MTX unless contraindicated) Failed to achieve an SDAI score of 26 Continue only if adequate response Swith to another drug Inadequate response Adverse event

45 Safety issues with the biologic DMARDs

46 Tuberculosis High background incidence and patient risk Increased risk with RA, conventional treatment and biologic DMARDs TNF inhibitors Reactivation of latent TB infection (LTBI) First few months after commencing treatment New TB infection Any time up tp 6 months after stopping biologics 50% extrapulmonary Incidence has been decreased by testing and treating LTBI

47 LTBI Screening CXR Tuberculin skin test (TST) 5mm positive Interferon gamma release assays (IGRA) Validity in high risk area not established Treat with INH or INH and rifampicin Commence biologic DMARD 1 month after starting LTBI treatment

48 High risk patients Consider long term INH

49 TB infection Continuous vigilance Routine screening not recommended No value in repeated TST or CXR

50 Infections in general Serious bacterial infections In trails rate similar to placebo Opportunistic Fungal Listeria and non-tuberculous mycobacterial infections. Contraindications to use of biologic DMARDs Chronic infected leg ulcers Septic arthritis in the preceding 12 months Septic arthritis of prosthetic joint Recurrent urinary or respiratory tract infections Indwelling urinary catheter Hypogammaglobulinaemia.

51 Infection risk Active infection, administration of a biologic drug should be delayed Perioperative use: Discontinue biologic DMARDs 3 to 5 times the half-life of the drug before surgery Resumed after good wound healing

52 Malignancy Patients with RA are at increased risk of lymphoma and other solid tumours Uncontrolled joint inflammation Biologic drugs do not seem to confer increased an risk of malignancy Recurrence of a malignancy No perceived change the prognosis of cancers that occur in patients using biologic therapies Biologic therapy be avoided in patients with a current or recent (<5years) diagnosis of a malignancy.

53 Viral hepatitis: Hepatitis B reactivation can occur in hepatitis B surface antibody (HBsAg) positive patients treated with MTX or biologic therapy Screening for viral hepatitis before starting treatment is recommended Hepatitis B vaccination should ideally be offered to non-immune patients before commencing DMARD treatment Hepatitis C-infected patients anti-tnf therapy and rituximab is considered safe

54 Vaccination: Vaccination can and should be given to patients on biologic DMARDs Live vaccines may not be given during treatment and should be given prior to starting treatment Attenuated vaccines Immune reaponse may be decreased Ideally long term vaccinations to be done before commencement of treatment

55 Figure 1: Algorithm for management of Rheumatoid Arthritis in South Africa Time frame RA therapy Safety issues Prompt initiation of therapy CXR HIV test Hepatitis B, C Frequent (1-3 monthly) visits until LDA achieved LDA/remission? Yes No Continue Consider vaccination Yes Continue Screen and treat cardio-vascular risks and osteoporosis LDA/remission? No 6 months Lower risk Consider TB risk Very high risk Screen for LTB Complete 1 month of TB prophylaxis before starting anti-tnf 6 months LDA/remission? INH prophylaxis for all regardless of PPD/IGRA Yes No Continue If positive, 6-9 months INH prophylaxis Vigilance for infection including TB

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