Predictors And Frequency of Achievement of Low Disease Activity or Remission with Methotrexate Monotherapy in Rheumatoid Arthritis

Background: While rheumatoid arthritis is the most commonly seen form of inflammatory arthritis world-wide, it is accompanied by chronic inflammation of the synovium, resulting in structural damage and disability. Methotrexate remains the primary first-line conventional synthetic csDMARD used for rheumatoid arthritis, also being advocated as a first-line treatment option for treat-to-target approaches owing to its established efficacy, especially in controlling the disease activity and halting structural development. Nonetheless, the achievement of remission or sustained LDA as a solo therapy, especially using methotrexate, is possible only for a limited proportion of patients, as evidenced by real-world data, where a wide variability is seen, especially according to baseline disease activity. Objectives: The aims of the present study were to find the rate of remission or LDA state after methotrexate monotherapy and to find the predictive factors of this rate in patients suffering from RA. Methodology: This uncontrolled open-labeled clinical trial was carried out in the Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from January to December 2019. The patients satisfying the American College of Rheumatology (ACR) criteria of RA published in 2010, who were unexposed to MTX, were started on subcutaneous injections of MTX, with a fixed weekly dose of up to 25 mg. Of a total of 105 patients, 91 patients completed the follow-up period of 6 months. The principal outcome measure was achievement of LDA or remission, based on Disease Activity Score-28 with C-reactive protein (DAS28-CRP). Secondary outcomes were Clinical Disease Activity Index (CDAI) response rates and achievement based on American College of Rheumatology 50% improvement criteria (ACR50). Results: 20.9% of patients met LDA and 18.7% met remission at 6 months of MTX monotherapy based on DAS28-CRP. In total, around 40% of patients met treat-to-target criteria for LDA or remission. Baseline activity level was significantly associated with achieving DAS28-CRP response (OR 0.09; 95% CI 0.02–0.46). There was also an association between HLA-DR4 SNP rs6457617 and CDAI response (p = 0.05). Conclusions: In this patient population, 40% of the patients attained LDA/remission state on methotrexate monotherapy. Baseline disease activity emerged as an important predictor of response, while genetic predictors such as HLA-DR4 SNPs could also affect response trajectory.