Safety and Efficacy of Baricitinib, Upadacitinib, and Sarilumab Implementation in Moderately-to-Severely Active Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Current Evidence.

This study aims to assess the efficacy and safety of newly approved Janus kinase (JAK) and interleukin-6 (IL-6) inhibitors in patients with moderately-to-severely active rheumatoid arthritis (RA) with inadequate response to or intolerance of conventional disease-modifying antirheumatic drugs. We conducted a systematic review and meta-analysis of all placebo-controlled randomized trials assessing baricitinib, sarilumab, and upadacitinib treatment in RA, published in PubMed and CENTRAL (Cochrane Central Register of Controlled Trials) databases up to October 2023. The study outcomes involved the American College of Rheumatology (ACR) 20%, 50%, and 70% responses, Health Assessment Questionnaire-Disability Index (HAQ-DI), Disease Activity Score in 28 joints (DAS28), serious adverse events, and adverse events leading to drug discontinuation. Twelve randomized controlled trials enrolling 5875 patients were selected for final analysis. Pooled analysis revealed that the implementation of baricitinib (RR = 1.77; 95% CI = 1.58-1.97; I = 21%), sarilumab (RR = 1.60; 95% CI = 1.33-1.93; I= 0%), and upadacitinib (RR = 1.99; 95% CI = 1.81-2.20; I = 15%) was associated with notable therapeutic improvement in RA patients as determined by the ACR20. Considering other efficacy outcomes (ACR50, ACR70, DAS28, HAQ-D), all tested interventions demonstrated a superiority to placebo. None of the tested treatment modalities incurred a higher risk of serious adverse events compared to placebo, yet drug discontinuation was more commonly encountered in baricitinib-treated patients. The newly approved JAK and IL-6 inhibitors, namely, baricitinib, upadacitinib, and sarilumab, seem to be effective in alleviating RA-induced clinical implications and thus improving quality of life. Nonetheless, safety issues could be a matter of concern in baricitinib use, while upadacitinib and sarilumab present an acceptable safety profile.