A retrospective study of efficacy of tofacitinib combined with bDMARDs in the treatment of rheumatoid arthritis patients with inadequate response to bDMARDs

Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation, joint swelling, and pain involving multiple joints. While biologic disease-modifying antirheumatic drugs(bDMARDs) and targeted synthetic DMARDs(tsDMARDs) are popular treatments for RA, there is limited research on their combined use. This study examined a cohort of RA patients who demonstrated inadequate response to bDMARDs and subsequently initiated combination therapy with tofacitinib and bDMARDs, assessing both the efficacy and safety profile of this therapeutic approach. Methods: In this study, we retrospectively collected the electronic medical records (EMR) of 56 adult patients with RA who were admitted to the Fourth Affiliated Hospital Zhejiang University School of Medicine between August 2018 to December 2022. All patients had received at least one bDMARD treatment for more than three months and still exhibited moderate to high disease activity. Tofacitinib 5mg bid was added to their original biological treatment in 28 cases, and other 28 cases switched to another bDMARD or tsDMARD as control group. Treatment was continued for 60weeks following the initiation of combination therapy. Changes in DAS28-CRP and ACR20 response rate at week 60 were collected and analyzed from baseline, while changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at weeks 4, 8, 12 followed by subsequent assessments every 12 weeks until the completion of the 60-week study period were also collected and analyzed. Results: After 60 weeks of treatment, the DAS28-CRP score in combined treatment group decreased significantly from a baseline of 5.16±0.91 (3.86~8.21) to 2.64±0.85 (1.39~5.13), with remission achieved by 19 patients (67.9%) and low disease activity achieved by 5 patients (17.9%). The DAS28-CRP in the control group exhibited a decrease from 5.20±0.79 (3.88~7.21) at baseline to 3.23±1.27 (1.53~5.59). 10 patients (35.7%) achieved remission, while another 10 patients (35.7%) achieved low disease activity. The ACR20 response rate was 85.71% in the combined treatment group, whereas it was 71.43% in the control group. Additionally, both ESR and CRP levels decreased significantly during the course of treatment without any reported adverse events leading to discontinuation. Conclusion: Our findings offer some evidence, supporting the effectiveness and safety of combining bDMARD with JAKi tofacitinib in RA patients who have an inadequate response to bDMARD monotherapy. This combination effectively manages disease activity while maintaining a relatively low and manageable incidence of adverse events.Further prospective randomized controlled trials with large sample sizes are anticipated to provide evidence-based medical support.