SAT0214 Effectiveness of a randomized step-down to methotrexate or leflunomide maintenance therapy in patients with low disease activity, 40 weeks after starting combined methotrexate-leflunomide remission induction therapy in early rheumatoid arthritis: results from the carera trial
Authors: V. Stouten, S. Michiels, A. Belba, R. Westhovens, P. Verschueren
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Combination of methotrexate, leflunomide and a short-term course of glucocorticoids is an effective initial treatment strategy for early rheumatoid arthritis (ERA) (1). However, evidence concerning further maintenance or step-down strategies after achieving remission or low disease activity is lacking. <h3>Objectives:</h3> To evaluate efficacy and tolerability of a step-down to methotrexate versus leflunomide monotherapy in ERA patients achieving low disease activity (LDA) after induction therapy with a combination of both. <h3>Methods:</h3> The care in ERA (CareRA) trial is a 2-year randomized pragmatic superiority trial comparing different remission induction strategies in ERA. For the purpose of the current sub-study, DMARD-naïve ERA patients initially randomized into the COBRA Avant-Garde arm (methotrexate 15 mg weekly+ leflunomide 10 mg daily + prednisone step-down from 30 mg) were re-randomized, after a period of 40 to 52 weeks, to a methotrexate 15 mg weekly or leflunomide 20 mg daily maintenance therapy when achieving LDA (DAS28-CRP≤3.2). Disease activity, functionality and X-ray damage were registered. Efficacy of both regimens was compared at week 65 after re-randomization as well as their safety profiles and drug retention rates (ITT analysis). <h3>Results:</h3> We re-randomized 58 patients to either methotrexate (n=32) or leflunomide (n=26) monotherapy. At re-randomization 81.2% of patients in the methotrexate group (26/32) was in remission (DAS28-CRP&lt;2.6), versus 92.3% (24/26) in the leflunomide group (p=0.225). At 65 weeks post re-randomization significantly more patients achieved DAS28-CRP remission in the methotrexate group (93.8%) than in the leflunomide group (73.1%) (p=0.031). Patients re-randomized to methotrexate also achieved more frequently a state of LDA measured by DAS28-CRP, CDAI and SDAI in comparison to patients re-randomized to leflunomide (table 1). Safety analysis after re-randomization did not show differences between groups with regards to number or type of adverse events (AEs). Numbers of patients with AEs related to study medication were comparable (31.2% in the methotrexate and 34.6% in the leflunomide group). Throughout these 65 weeks 71.9% of patients in the methotrexate and 53.8% (p=0.098) in the leflunomide arm remained on the assigned DMARD monotherapy. At the end of the study, in patients remaining on methotrexate monotherapy the mean dose was 15.3 mg weekly versus a mean dose of 17.1 mg daily in patients remaining on leflunomide monotherapy. <h3>Conclusions:</h3> Step-down to methotrexate monotherapy instead of leflunomide monotherapy seems more efficacious, is well tolerated and has a good drug retention rate in ERA patients in LDA after combination therapy with methotrexate and leflunomide. <h3>Reference:</h3> 1) Verschueren P, et al. Ann Rheum Dis2017;76(3):511–520. <h3>Disclosure of Interest:</h3> V. Stouten: None declared, S. Michiels: None declared, A. Belba: None declared, R. Westhovens: None declared, P. Verschueren Grant/research support from: unrestricted Pfizer chair for management of early RA