Risk of Adverse Drug Events Observed with Baricitinib 2mg Versus Baricitinib 4mg Once Daily for the Treatment of Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract

On 23 April 2018, the Food and Drug Administration-based Advisory Committee approved the use of baricitinib 2mg for the treatment of rheumatoid arthritis and suggested the possibility of serious adverse events associated with baricitinib 4mg. Hence, we aimed to systematically compare the risk of adverse drug events observed with baricitinib 2mg versus 4mg for the treatment of patients with rheumatoid arthritis. Electronic databases including the Cochrane library, MEDLINE, EMBASE and http://www.ClinicalTrials.gov were searched for relevant English publications until April 2018. Adverse drug events at 12weeks and 24weeks were considered as the clinical endpoints. RevMan 5.3 software was used to analyze the data whereby risk ratios (RR) and 95% confidence intervals (CI) were calculated. Four trials consisting of a total of 959 participants were included in this analysis. At 12weeks, no significant difference was observed between 2mg and 4mg baricitinib for serious adverse events (RR 1.33; 95% CI 0.63-2.78; p = 0.46), any adverse events after the start of therapy (RR 1.09; 95% CI 0.98-1.21; p = 0.13), discontinuation of drugs due to adverse events (RR 1.19; 95% CI 0.61-2.34; p = 0.60), malignancies (RR 3.03; 95% CI 0.12-73.90; p = 0.50), and major adverse cardiac events (RR 2.95; 95% CI 0.12-71.91; p = 0.51). Infections including herpes zoster infections and serious infections were also similarly manifested. At 24weeks, serious adverse events (RR 1.84; 95% CI 1.02-3.30; p = 0.04) were significantly higher with baricitinib 4mg compared with the 2-mg dosage. However, total adverse events after the start of therapy, discontinuation of drug due to adverse events, malignancies, major adverse cardiac events, infections including herpes zoster, and serious infections were not significantly different between the two doses. No significant differences in adverse drug events were observed between baricitinib 2mg and 4mg at 12weeks' follow-up. However, this analysis showed the risk of serious adverse events to be significantly higher with baricitinib 4mg compared with baricitinib 2mg at 24weeks' follow-up. This hypothesis should be confirmed in larger trials with longer follow-up time periods.