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Review
. 2024 Dec 27;16(12):e76466.
doi: 10.7759/cureus.76466. eCollection 2024 Dec.

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

Giannis Meziridis  1 , Penelope Sidiropoulou  2 , Chrysa Pourzitaki  3 , Anna-Bettina Haidich  4 , Georgia Tsaousi  5
Affiliations
Review

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

Giannis Meziridis et al. Cureus. .

Abstract

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; I2 = 21%), sarilumab (RR = 1.60; 95% CI = 1.33-1.93; I2 = 0%), and upadacitinib (RR = 1.99; 95% CI = 1.81-2.20; I2 = 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.

Keywords: baricitinib; interleukin-6 inhibitors; jak inhibitors; meta-analysis; rheumatoid arthritis; sarilumab; systematic review; upadacitinib.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Flow diagram showing the results of the search and reasons for the exclusion of studies according to PRISMA-IPD guidelines.
PRISMA-IPD: Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data; RCTs: randomized control trials; IPD: individual participant data; ACR: American College of Rheumatology; DAS28: Disease Activity Score in 28 joints; hsCRP: high-sensitivity C-reactive protein; HAQ-DI: Health Assessment Questionnaire-Disability Index.
Figure 2
Figure 2. Risk of bias assessment with RoB-2 tool.
RoB-2: Risk of Bias 2. References [13-24].
Figure 3
Figure 3. DAS28 at week 12.
DAS28: Disease Activity Score in 28 joints.
Figure 4
Figure 4. HAD-DI at week 12.
HAQ-DI: Health Assessment Questionnaire-Disability Index.
See this image and copyright information in PMC

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