Abstract

Background:Among patients with psoriatic arthritis (PsA), there remains a considerable confusion regarding the effectiveness of conventional synthetic DMARDs (csDMARDs), especially methotrexate (MTX). The availability of biologic DMARDs and targeted synthetic DMARDs have revolutionised the management of psoriatic disease; however, it comes with a significant cost burden. We believe that combination of DMARDs, especially combining MTX and Leflunomide (LEF) provides a valuable low-cost treatment option for patients with PsA after failure of MTX monotherapy. Hence, in our practice, we are inclined to use combination of potent DMARDs after MTX failure, prior to considering biologic therapies. Little is known about the combination use of LEF and MTX in PsA, especially in the context of drug retention time and tolerability.Objectives:We aimed to review our PsA cohort data especially examining the drug retention of first-line csDMARD monotherapy and combination csDMARDs.Methods:In our centre, MTX is a preferred first line csDMARD, unless contraindicated, and patients are followed up with a protocol on 4-6 weekly basis unless complete remission is achieved. MTX if needed is escalated to the maximum tolerated dose (up to 25mg/week), and if PsA is still active then preferably LEF is added (usual starting dose for add-on therapy is 10mg a day and if needed escalated to 20mg a day, without any loading dose). Other csDMARDs, such as sulphasalazine are used, if needed. For this study, after written-informed consent, only those adult patients were included who had a follow up of at least 6 months with our rheumatology services, and were fulfilling CASPAR criteria. Moreover, only patients who were DMARD-naïve (no prior DMARD therapy for any cause, including psoriasis), and initiated DMARD as monotherapy after 1 April 2018 were included. If any patient had already been on any DMARDs prior to attending our rheumatology services was excluded.Results:A total of 81 PsA patients [mean age 45.6±6 years; 52% male; mean PsA disease duration=9±4 years; 35% with dactylitis, 42% with enthesitis, 17% with sacroiliitis, median current PASI=2.6, median number of swollen joints=8.0, median number of tender joints= 11.0] fulfilled the inclusion and exclusion criteria. As regards first-line csDMARD monotherapy, 88% (n=71) of patients were commenced on MTX. In total, 79% (n=56 out of 71) of patients who were started on MTX as their first-line csDMARD therapy failed this monotherapy during follow-up (51=ineffective, 5=intolerance). After a median follow-up of 22 months, MTX median drug retention among all MTX monotherapy users (n=71) was only 7 months (IQR 5-7); and among MTX failures (n=56), MTX monotherapy median drug retention was 6.0 months (IQR 4-8). Eighty percent (n=45 out of 56) of the MTX monotherapy failure cohort was started on combination therapy of MTX and LEF (combo MTX+LEF); among them, only 7 patients needed escalation of therapy to bDMARDs, and the rest are still using combo MTX+LEF. It was noted that to date median drug retention time of combo MTX+LEF has been 8 months (IQR 7-11), and 84% (n=38 out of 45) of these patients are still using this combo therapy. Significantly more patients managed to continue the combo MTX+LEF therapy compared to MTX monotherapy (84% vs. 21%, p<0.001)Conclusion:Among csDMARD naïve PsA patients, 79% of patients failed MTX monotherapy with median drug retention time of only 6 months. Combination of MTX and LEF was well tolerated and had good drug retention time, with 84% of patients having ongoing treatment to date. Our data provides initial evidence that MTX and LEF combination therapy could be an effective treatment option for PsADisclosure of Interests:Muhammad Haroon Speakers bureau: Roche, Novartis, Grant/research support from: Abbvie, Pfizer, Shabnam Batool: None declared., Sadia Asif: None declared., Farzana Hashmi: None declared., Saadat Ullah: None declared.

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