Efficacy of baricitinib for the treatment of systemic lupus erythematosus patients: A meta‐analysis of randomized controlled trials

Abstract

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal autoantibody production, inflammation, and organ damage. Most SLE treatment strategies aim to induce remission or reduce disease activity while avoiding flares. Baricitinib has been used effectively to manage various inflammatory diseases, and some randomized controlled trials (RCT) have shown that it is beneficial in treating SLE. The current study aims to assess the efficacy of baricitinib in treating SLE patients.Materials and MethodsVarious databases such as PubMed, Scopus, and Science Direct were searched to obtain eligible studies for the present meta‐analysis. Data such as baseline characteristics of patients, doses of the baricitinib, follow‐up duration, and treatment outcome in the form of SLE responder index‐4 (SRI‐4) and lupus low disease activity state (LLDAS) were extracted. Combined odds ratio, 95% confidence interval, and probability values were calculated to study the efficacy of baricitinib in treating SLE patients. A p‐value less than .05 was taken as significant. Comprehensive meta‐analysis v3 was used for all analyses.ResultsThree articles were found eligible for the present meta‐analysis comprising 614 patients with placebo, 614 SLE patients receiving 4 mg, and 621 patients with 2 mg of baricitinib. Meta‐analysis revealed a beneficial effect of 4 mg baricitinib in SLE patients compared to placebo, as measured by an increase in the SRI‐4 (p = .006, OR = 1.370) and LLDAS (p = .083, OR = 1.252) rates. In contrast to the placebo group, however, patients receiving 2 mg of baricitinib exhibited no significant improvement. The trial sequential analysis revealed the need for additional RCTs to determine the role of baricitinib in treating SLE patients.ConclusionIn treating SLE patients, administrating a higher dose of baricitinib (4 mg) may be effective. However, additional RCTs in different populations with larger sample sizes are required to validate our findings.

Outlook of the jakinibs in systemic lupus erythematous after baricitinib failed

“…The primary efficacy end point, SRI-4 at Week 52, was met in the BRAVE-I study (57% vs. 46%; p = .02) with baricitinib 4 mg but not in BRAVE-II (47.4% vs. 45.6%). Secondary end points that included SRI-4 response at Week In a recent issue of International Journal of Rheumatic Diseases, Panda et al 24 performed a meta-analysis of the above three RCTs 20,22,23 and reported that baricitinib 4 mg/day was superior to PBO in terms of achievement of SRI-4 but not LLDAS. Serious AEs were significantly more common with baricitinib 4 mg than PBO.…”

“…In fact, four other meta-analyses of the same RCTs were also published at round the same time period (August to November 2023). [25][26][27][28] Interestingly, the results from these five meta-analyses [24][25][26][27][28] are somewhat different. While a reduction in SLEDAI by ≥4 points and remission of skin/joint disease were significantly more frequent in the baricitinib 4 mg group 25,27,28 after data pooling, the superiority of baricitinib 4 mg to PBO in the SRI-4 response was only demonstrated in three meta-analyses 24,26,28 but not in the other two.…”

“…[25][26][27][28] Interestingly, the results from these five meta-analyses [24][25][26][27][28] are somewhat different. While a reduction in SLEDAI by ≥4 points and remission of skin/joint disease were significantly more frequent in the baricitinib 4 mg group 25,27,28 after data pooling, the superiority of baricitinib 4 mg to PBO in the SRI-4 response was only demonstrated in three meta-analyses 24,26,28 but not in the other two. 25,27 The reason for the discrepancy of these studies is not immediately apparent but all the reported a significantly increased risk of serious AEs and/or in the baricitinib 4 mg group.…”

“…Although pooling of data from the three pivotal RCTs favors benefits of baricitinib 4 mg, the failure of achievement of the related secondary end points cannot be explained. The difference in the pooled result of the SRI-4 response in the five metaanalyses [24][25][26][27][28] further adds to the confusion regarding the efficacy of baricitinib in SLE. Moreover, the increased risk of serious infections with baricitinib is a major concern in patients with SLE, along with the potential increase in cardiovascular and malignancy risk with the jakinibs as demonstrated in the Oral Surveillance study of tofacitinib in rheumatoid arthritis over 4 years.…”