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



On 23 April 2018, the Food and Drug Administration-based Advisory Committee approved the use of baricitinib 2 mg for the treatment of rheumatoid arthritis and suggested the possibility of serious adverse events associated with baricitinib 4 mg. Hence, we aimed to systematically compare the risk of adverse drug events observed with baricitinib 2 mg versus 4 mg for the treatment of patients with rheumatoid arthritis.


Electronic databases including the Cochrane library, MEDLINE, EMBASE and were searched for relevant English publications until April 2018. Adverse drug events at 12 weeks and 24 weeks 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 12 weeks, no significant difference was observed between 2 mg and 4 mg 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 24 weeks, serious adverse events (RR 1.84; 95% CI 1.02–3.30; p = 0.04) were significantly higher with baricitinib 4 mg 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 2 mg and 4 mg at 12 weeks’ follow-up. However, this analysis showed the risk of serious adverse events to be significantly higher with baricitinib 4 mg compared with baricitinib 2 mg at 24 weeks’ follow-up. This hypothesis should be confirmed in larger trials with longer follow-up time periods.

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Authors and Affiliations



FH and ZL were responsible for the conception and design, acquisition of data, analysis and interpretation of data, drafting the initial manuscript and revising it critically for important intellectual content. FH wrote this manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Corresponding author

Correspondence to Feng Huang.

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Ethical approval

Ethical approval was not applicable for this systematic review and meta-analysis.

Conflict of interest

Feng Huang and Zu-chun Luo declare that they have no competing interests.


No external funding was used in the preparation of this manuscript. This research was supported by the National Natural Science Foundation of China (nos. 81560046, 81760057) and Guangxi Natural Science Foundation (no. 2016GXNSFAA380002).

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Huang, F., Luo, Zc. Risk of Adverse Drug Events Observed with Baricitinib 2 mg Versus Baricitinib 4 mg Once Daily for the Treatment of Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. BioDrugs 32, 415–423 (2018).

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