ABS0399 A RANDOMIZED, OPEN-LABEL STUDY TO COMPARE THE EFFICACY AND SAFETY OF METHOTREXATE COMBINATION WITH LEFLUNOMIDE, SULFASALAZINE AND TOFACITINIB IN RHEUMATOID ARTHRITIS WITH METHOTREXATE INADEQUATE RESPONSE

Background: Treat-to-target treatment strategy in rheumatoid arthritis (RA) allows significant number of patients to achieve low disease activity, prevents progression of joint damage, improves physical function and quality of life [1]. Methotrexate is the initial disease modifying antirheumatic drugs (DMARDs) in most patients allowing disease control over 3-6 months. In patients with methotrexate inadequate response (IR), the choice of DMARDs is guided by presence of prognostic factors like high titer rheumatoid factor or anti-citrullinated peptide antibody, high disease activity, early joint damage and 2 or more conventional synthetic DMARDs (csDMARDs) failure [2]. Data on head-to-head comparison of combination of csDMARDs in RA is limited. Considering the cost-effectiveness of combination csDMARDs and the challenges of administering bDMARDs upfront especially in the Indian context, the present study was designed to evaluate the efficacy of methotrexate combination with Leflunomide, Sulfasalazine or Tofacitinib in RA with methotrexate IR. Objectives: To evaluate the efficacy of methotrexate combination with Leflunomide, Sulfasalazine and Tofacitinib in rheumatoid arthritis (RA) with methotrexate inadequate response. Methods: In this randomized, open-label, parallel arm clinical trial, RA patients were divided into 3 groups: A, B and C, receiving oral methotrexate 25 mg/week along with Leflunomide 20 mg/d, Sulfasalazine 2 g/d and Tofacitinib 5mg twice daily, respectively. The primary endpoint was American College of Rheumatology (ACR) 20 response at 16 week. The secondary endpoints included ACR50 and ACR70 response and EULAR Good response by disease activity score (DAS) 28-CRP, and Health Assessment Questionnaire (HAQ). Serum interleukin (IL)-6 levels were assayed at baseline and follow-up. Intention-to-treat analysis was performed. Results: Eighty-three patients were included (group A=32, B=25 and C=26, patients). The ACR20 response was 63%, 56% and 92% in group A, B and C, respectively (p= 0.0001). The ACR50 and ACR70 response were significantly higher in Tofacitinib group (ACR50: 44%, 52% and 92%; p=0.0002 and ACR70: 21%, 20% and 57% of patients; p=0.0001 in group A, B and C, respectively). All three groups showed significant reduction in serum IL-6 levels, CRP, ESR and HAQ from baseline to week 16. There was no major adverse events. Conclusion: Tofacitinib showed significant improvement in disease activity measures and patient-reported outcomes in RA patients with methotrexate inadequate response compared to Leflunomide and Sulfasalazine. REFERENCES: [1] Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet 2004;364:263-9. [2] Smolen JS, Landewé RBM, Bergstra SA, Kerschbaumer A, Sepriano A, Aletaha D, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis 2023;82:3-18. Figure 2Primary and Secondary Endpoints at week 16 Figure 1Study Design Acknowledgements: INDIAN RHEUMATOLOGY ASSOCIATION. Disclosure of Interests: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.