Safety of baricitinib 24 weeks 4 mg or 2 mg for the treatment of rheumatoid arthritis: A meta-analysis of randomized controlled trials.

Backgrounds: Baricitinib, an oral selective inhibitor of Janus kinase 1 and 2, is approved for moderate and severe rheumatoid arthritis (RA) with insufficient response to conventional synthetic disease-modifying antirheumatic drugs. The study evaluated the safety of baricitinib 24 weeks 4 mg or 2 mg for the treatment of RA.

Methods: The net change (least squares mean [LSM]) of alanine aminotransferase (ALT), creatinine, low-density lipoprotein cholesterol (LDL-C) levels from baseline with the comparison of baricitinib versus placebo was pooled, respectively. The risk ratios (RR) of serious advanced events (SAEs), major cardiovascular events (MACEs), infection, serious infection, and advanced events (AEs) at the end of treatment across groups were compared.

Results: Five randomized controlled trials with 2901 patients were included in the summary analysis. Results showed that baricitinib 4 mg significantly increased ALT and creatinine levels, the net LSM change was respectively 3.59 U/L with 95% confidence interval (CI) (1.75-5.43), 4.25 µmol/L with 95% CI (3.38-5.12), however, baricitinib 2 mg of ALT and creatinine levels were not significantly different. Baricitinib 4 mg and 2 mg significantly increased LDL-C levels, the net LSM change was respectively 11.44 mg/dL with 95% CI (6.08-16.80), 8.70 mg/dL with 95% CI (4.19-13.20). Baricitinib 4 mg significantly increased the incidence of infection, the pooled RR (95% CI) was 1.29 (1.13-1.47), and baricitinib 2 mg was not significantly different. However, the pooled RRs of SAEs, MACEs, and serious infection were not statistically significant across groups. The pooled RRs of AEs were not statistically significant between baricitinib 4 mg and 2 mg.

Conclusions: This study confirmed that patients with RA taking 4 mg baricitinib increased levels of ALT, creatinine, as well as an increased risk of infections, compared with those taking 2 mg baricitinib. Both 2 mg and 4 mg also increased the level of LDL-C, but it increased the most severely at 4 mg baricitinib. However, the incidence of SAEs, MACEs, and serious infection was not significantly different in patients treated with baricitinib 4 mg and 2 mg compared with placebo, the incidence of AEs was not significantly different between baricitinib 4 mg and 2 mg.