EULAR Recommendations for the Management of PsA

Transcription

1 EULAR Recommendations for the Management of PsA

2 Scope Background on PsA EULAR treatment recommendations Brief look at GRAPPA recommendations Summary of key points

3 Background on PsA PsA is a heterogeneous disease - broad phenotype of joint involvement (peripheral and axial) - spectrum of extraarticular manifestations ie. dactylitis and enthesopathy Studies on PsA demonstrated benefits and efficacy of synthetic DMARDs and TNF inhibitors Recently recommendations for PsA treatments presented by GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) - comprehensive, special focus on psoriasis

4 Background on PsA 2010 EULAR developed own set of recommendations for Mx of PsA to provide clinicians with concise, easy-tofollow guidelines on - Optimal use of available therapies - Clear treatment strategies for PsA Reasons why recommendations were developed 1) Efficacy of synthetic DMARD and role of glucocorticoid (GC) debatable 2) Combination therapy of synthetic DMARD or synthetic DMARD + biological agents relatively under researched 3) No clear measure for disease activity for PsA

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6 EULAR PsA Recommendations Methods Task force aggregate available information on disease Mx in PsA and develop into practical recommndations Expert committee 28 rheumatologists, 2 patients, 1 infectious disease specialist, 1 dermatologist, 1 physiotherapist and 2 rheumatology fellows Committee members were from 14 European countries and the US 2 expert meetings Systematic literature reviews and extensive discussion Vote obtained from experts on level of agreement for each recommendation 0 = total disagreement, 10 = total agreement

7 EULAR PsA Recommendations Overarching Principles PsA is a heterogeneous and potentially severe disease, which may require multidisciplinary treatment Treatment of PsA patients should aim at the best care, based on shared decisions made by the patient and rheumatologist Rheumatologists are the specialists who should primarily care for the musculoskeletal manifestations of PsA; in the presence of clinically significant skin involvement, a rheumatologist and a dermatologist should collaborate in diagnosis and management The primary goal of treating patients with PsA is to maximize longterm health-related quality of life through control of symptoms, prevention of structural damage, normalisation of function and social participation Abrogation of inflammation, targeted at remission, is an important component to achieve these goals Patients should be regularly monitored and treatment should be adjusted appropriately

8 10 recommendations on drug management and treatment strategies for PsA

9 Recommendation 1 (NSAID) In patients with PsA, nonsteroidal anti-inflammatory drugs may be used to relieve musculoskeletal signs and symptoms NSAID used as first-line treatment, although data on benefit of NSAID in PsA limited Efficacious on joint symptoms, but no demonstrated efficacy on skin lesions CVS and GI risk taken into account Not everyone with signs and Sx require NSAID Rx, some may respond to analgesics and do not need NSAID

10 Recommendation 1 Encourage lowest dose and shortest treatment duration possible with NSAID, in view of potential toxicity COX2 inhibitors are equally effective as nonselective NSAID in PsA

11 Recommendation 2 (DMARD) In patients with active disease (many swollen jts, structural damage, high ESR/CRP and/or clinically relevant extraarticular manifestations), treatment with DMARD (MTX, SSZ, Leflunomide) should be considered at an early stage Few data for making decision on when to start systhetic DMARD and who should be treated with DMARD Based on prognostic factors, pts with active disease and potential poor prognosis should be started on DMARD

12 Recommendation 2 Active disease - one or more tender and inflamed joint and/or tender enthesis and/or dactylitic digit and/or inflammatory back pain For introduction of synthetic DMARD only joint involvement Poor prognosis refers to - 5 or more actively inflamed joints - high ESR/CRP - radiographic damage that is progressing - previous use of glucocorticoids - loss of function and diminished quality of life

13 Recommendation 2 Choice of synthetic DMARD recommended Methotrexate as first-choice Besides MTX, other synthetic DMARD considered - sulfasalazine, leflunomide, ciclosporin A Treatment with synthetic DMARD should be considered at an early stage Synthetic DMARD not efficacious for treating enthesitis and axial disease Prevention of structural damage in PsA - None of synthetic DMARD tested for and/or demonstrated structural efficacy in PsA DMARD combinations - Lack of evidence on efficacy of synthetic DMARD combinations, may be considered

14 Recommendation 3 In patients with active PsA and clinically relevant psoriasis (psoriasis with impact on QoL), a synthetic DMARD that also improves psoriasis such as MTX, is the preferred choice Apart from MTX, other DMARD shown efficacy in improving psoriasis include sulfasalazine, leflunomide and ciclosporin A

15 Recommendation 4 (corticosteroids) Local injections of corticosteroids should be considered as adjunctive therapy in PsA. Systemic steroids at the lowest effective dose may be used with caution IA steroids efficacious for mono/oligoarthritis or single joint flares, in otherwise well-controlled polyarthritis Steroid injections useful for enthesitis and dactylitis

16 Recommendation 4 What about systemic steroids in Rx of PsA? Fear that systemic steroids may result in psoriasis flare No evidence from clinical trials on efficacy of systemic steroids in Rx of PsA Task force recommended Systemic steroids remain a therapeutic option, although should be used with caution, possibility of psoriasis flare Systemic steroids should be tapered when feasible. When tapering, attention to potential worsening of psoriasis (rebound)

17 Recommendation 5 (TNF inhibitors) In patients with active arthritis and an inadequate response to at least one synthetic DMARD, such as MTX, therapy with a TNF inhibitor should be commenced A patient considered a treatment failure (to synthetic DMARD) when fails to achieve treatment target of low disease activity usually by 3-6 months TNF inhibitors can be considered if disease is active (swollen joints and/or at least moderate disease activity and/or active disease with impaired function or QoL)

18 Recommendation 5 (TNF inhibitors) TNF inhibitors (adalimumab, etanercept, infliximab, golimumab) - demonstrated efficacy in PsA (skin and joint inv) - preventing radiographic damage In terms of joints, no differences in efficacy of various TNFi (not based on head-to-head trials) However for skin, seems that efficacy of Etanercept on psoriasis lower, or slower onset, than antibodies targeting TNF (no head-to-head trials) Other biologics (ustekinumab, rituximab, abatacept, tocilizumab) - Insufficient data to support use in treatment of PsA

19 Recommendation 5 (TNF inhibitors) TNFi + synthetic DMARD vs. TNFi monotherapy - To date, no data showing superiority In all trials of TNF inhibitors in PsA, MTX allowed but not required Half patients were on TNF inhibitor monotherapy without concomitant MTX Data for patients receiving and not receiving MTX were comparable

20 Recommendation 6 (enthesitis/dactylitis) In patients with active enthesitis and/or dactylitis and insufficient response to NSAIDs or local steroid injections, TNF inhibitors may be considered DMARD not efficacious for enthesitis and/or dactylitis Efficacy of TNF inhibitors has been reported in several trials No definition of active disease in this case Task force suggested to focus on quality of life. To exercise clinical judgement, aim to improve physical disability and QoL. Not to treat all such patients with TNF inhibitors.

21 Recommendation 7 (axial disease) In patients with predominant axial disease that is active and has insufficient response to NSAIDs, TNF inhibitors should be considered DMARD not efficacious for axial disease TNF inhibitors can be considered even if no synthetic DMARD have been tried In PsA, efficacy of TNF inhibitor on axial disease has been reported only in observational studies Task force recommends following established recommendations for Ankylosing Spondylitis

22 Recommendation 8 TNF inhibitor therapy might exceptionally be considered for a very active patient naïve of DMARD (many swollen joints, structural damage in presence of inflammation, and/or clinically relevant extraarticular manifestations, esp. extensive skin involvement) In certain and highly selected patients, may be a place for TNFi as first-line treatment Patients with contraindications for synthetic DMARD, poor prognostic factors with severe psoriasis or severe extra-articular manifestations with a professional need for very rapid improvement This recommendation is expert opinion

23 Recommendation 9 In patients who fail to respond adequately to one TNF inhibitor, switching to another TNF inhibitor agent should be considered Derived from studies indicating good efficacy of a second TNF inhibitor in PsA Extrapolated from data available regarding switches in TNF inhibitors in RA

24 Recommendation 10 When adjusting therapy, factors apart from disease activity, such as comorbidities and safety issues, should be taken Reflects a balance between efficacy and safety of treatment Physicians must be aware of potential adverse effects of treatment

25 EULAR PsA Recommendations EULAR Treatment Algorithm for PsA

26 EULAR PsA Recommendations EULAR Treatment Algorithm for PsA Continued

27 EULAR PsA Recommendations Conclusions The best evidence for efficacy is available for 3 synthetic DMARDs (methotrexate, leflunomide, and sulfasalazine) and 4 TNF inhibitors (adalimumab, etanercept, golimumab, infliximab) Modern therapy for PsA should be target oriented and governed by strategic treatment approach In line with recommendations in RA, the therapeutic goal should be to achieve remission or at least low disease activity, if remission cannot be attained

28 EULAR PsA Recommendations Conclusions Monotherapy with all TNF inhibitors usually leads to complete cessation of erosion progression, and these agents appear to prevent disease progression Limitations of recommendations - Do not address juvenile PsA and patients with psoriasis and some joint pain - Do not take into account topical treatments and non-pharmacologic therapy

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30 GRAPPA Treatment Recommendations for PsA Conducted by Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)1 70 rheumatologists and dermatologists Evidence-based review of effects of therapy on different PsA clinical domains 2 Establish diagnosis of PsA Peripheral arthritis Initiate therapy: NSAIDs IA steroids DMARDs ((MTX, CsA, SSZ, LEF) Biologics (antitnfs) Skin and nail disease Initiate therapy: Topicals PUVA/UVB Systemics (MTX, CsA, etc.) Biologics (antitnfs) Axial disease Initiate therapy: NSAID Physiotherapy Biologics (antitnfs) Dactylitis Initiate therapy: NSAID Injection Biologics (antitnfs) Reassess response to therapy and toxicity 1. Ritchlin C, et al. ARD 2009; 68: Enthesitis Initiate therapy: NSAID Injection Biologics (antitnfs)

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34 GRAPPA Recommendations: Assessment of PsA Severity Mild Moderate Severe <5 joints No damage on X-ray No LOF QOL-minimal impact Pt evaluation mild 5 joints (S or T) damage on X-ray IR to mild Rx Moderate LOF Moderate impact on QoL Pt evaluation moderate 5 joints (S or T) severe damage on X-ray IR to mild-moderate Rx Severe LOF Severe impact on QoL Pt evaluation severe Skin disease BSA <5 PASI <5 Asymptomatic Non-response to topicals DLQI, PASI <10 BSA >10 DLQI >10 PASI >10 Spinal disease Mild pain No loss of function Loss of function or BASDAI >4 Failure of response Enthesitis 1 2 sites No loss of function >2 sites or loss of function Loss of function or >2 sites and failure of response Dactylitis Pain absent to mild Normal function Erosive disease or loss of function Failure of response Peripheral arthritis 1. Ritchlin C, et al. ARD 2009; 68:

35 Rationale for Leveraging EULAR Recommendations Published more recently than GRAPPA recommendations Many of the same authors More up-to-date data utilized GRAPPA recommendations include a product no longer on the market Streamlined approach with similar flow to RA recommendations Some of the GRAPPA recommendations favoured other anti TNFs for individual EAM treatment EULAR recommendations note the poorer results of etanercept in treating skin disease

36 Summary of Key Points EULAR recommendations reflect the current state of evidence and thought in the area of PsA management Provides clinicians an easy-to-follow guidance on available therapies along with treatment strategies for PsA

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