Intensive therapy and remissions in rheumatoid arthritis: A systematic review

Background: We systematically reviewed the effectiveness of intensive treatment strategies in achieving remission in patients with both early and established Rheumatoid Arthritis (RA). Methods: A systematic literature review and meta-analysis evaluated trials and comparative studies reporting remission in RA patients treated intensively with disease modifying anti-rheumatic drugs (DMARDs), biologics and Janus Kinase (JAK) inhibitors. Analysis used RevMan 5.3 to report relative risks (RR) in random effects models with 95% confidence intervals (CI). Results: We identified 928 publications: 53 studies were included (48 superiority studies; 6 head-to-head trials). In the superiority studies 3013/11259 patients achieved remission with intensive treatment compared with 1211/8493 of controls. Analysis of the 53 comparisons showed a significant benefit for intensive treatment (RR 2.23; 95% CI 1.90, 2.61). Intensive treatment increased remissions in both early RA (23 comparisons; RR 1.56; 1.38, 1.76) and established RA (29 comparisons RR 4.21, 2.92, 6.07). All intensive strategies (combination DMARDs, biologics, JAK inhibitors) increased remissions. In the 6 head-to-head trials 317/787 patients achieved remission with biologics compared with 229/671 of patients receiving combination DMARD therapies and there was no difference between treatment strategies (RR 1.06; 0.93. 1.21). There were differences in the frequency of remissions between early and established RA. In early RA the frequency of remissions with active treatment was 49% compared with 34% in controls. In established RA the frequency of remissions with active treatment was 19% compared with 6% in controls. Conclusions: Intensive treatment with combination DMARDs, biologics or JAK inhibitors increases the frequency of remission compared to control non-intensive strategies. The benefits are seen in both early and established RA.