Clinical Rheumatology

, Volume 38, Issue 2, pp 523–534 | Cite as

Adverse drug events associated with 5mg versus 10mg Tofacitinib (Janus kinase inhibitor) twice daily for the treatment of autoimmune diseases: A systematic review and meta-analysis of randomized controlled trials

  • Feng HuangEmail author
  • Zu-chun Luo
Original Article


Several recently published clinical trials have shown tofacitinib to be effective in the treatment of autoimmune diseases. This drug is commonly prescribed either in a 5-mg or in a10-mg dosage twice daily. In this review, we aimed to systematically compare the adverse drug events which were observed with 5 mg versus 10 mg tofacitinib for the treatment of autoimmune diseases. MEDLINE, EMBASE, the Cochrane library, and were searched (from March to April 2018) for suitable English publications (published before April 2018). The inclusion criteria were as follows: randomized controlled trials, autoimmune disorders (rheumatic arthritis, psoriatic arthritis, moderate to severe psoriasis, and ankylosing spondylitis), and comparison of adverse drug events associated with 5 mg versus 10 mg tofacitinib. This study had follow-up time periods of 3 months and ≥ 6 months. Statistical analysis was carried out by RevMan 5.3 whereby risk ratios (RRs) and 95% confidence intervals (CIs) were generated. A total number of 4287 participants were included (2144 versus 2143 participants who received 5 mg and 10 mg tofacitinib twice daily respectively). The results showed that at 3 months, similar risks of adverse drug events, serious adverse events, and adverse events leading to drug discontinuation were observed with 5 mg versus 10 mg tofacitinib (RR 1.04, 95% CI 0.98–1.10; P = 0.17, I2 = 0%; RR 1.06, 95% CI 0.77–1.48; P = 0.71, I2 = 0%; and RR 1.06, 95% CI 0.78–1.43; P = 0.73, I2 = 32%, respectively). The other outcomes including serious infection events, adjudicated herpes zoster infection, adjudicated opportunistic infection, mild and severe neutropenia, malignancies, and adjudicated major adverse cardiovascular events were also similarly manifested. However, a decreased level of hemoglobin significantly favored 5 mg tofacitinib (RR 1.75, 95% CI 1.19–2.58; P = 0.005, I2 = 49%). Even at a follow-up time period of ≥ 6 months, adverse drug events, serious adverse events, adverse drug events leading to drug discontinuation, and serious infection were still similarly observed. According to this current review, both dosages of tofacitinib were safe to use. Even if similar adverse drug events were observed with 5 mg versus 10 mg tofacitinib twice daily for the treatment of autoimmune disorders, anemia was more prominent with 10 mg tofacitinib at a 3 month follow-up. Nevertheless, future studies based on a larger population size with longer follow-up time periods should further be considered.


Adverse drug events Anemia Autoimmune disorders Janus kinase inhibitor Tofacitinib 



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.

Authors’ information

Dr. Feng Huang (M.D) is the first author.

Authors’ contributions

FH and ZL were responsible for the conception and design, acquisition of data, analysis and interpretation of data, and drafting the initial manuscript and revising it critically for important intellectual content. FH wrote and approved the final manuscript.


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

Compliance with ethical standards




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Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  1. 1.Institute of Cardiovascular Diseases and Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Disease Control and Prevention and Guangxi Clinical Research Center for Cardio-cerebrovascular DiseasesThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina
  2. 2.Department of Internal Medicine EducationThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina

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