Efficacy and safety of tacrolimus in patients with rheumatoid arthritis – A systematic review and meta-analysis

Abstract

Objectives

To evaluate the efficacy and safety of tacrolimus in adult patients with rheumatoid arthritis (RA) by using the GRADE approach.

Methods

We searched PubMed, Japana Centra Revuo Medicina Web (Ichu-shi web), and the Cochrane Database of Systematic Reviews. Articles fulfilling the predefined inclusion criteria were appraised and used for meta-analysis. The primary outcomes were American College of Rheumatology 20 (ACR20) and serum creatinine elevation. Other outcomes included ACR50, ACR70, changes in C-reactive protein, modified Health Assessment Questionnaire Disability Index, gastrointestinal disorders, metabolic and nutritional disorders, and infections and infestations.

Results

We identified five randomized controlled studies, four of which compared tacrolimus to placebo and were included in the meta-analysis. The risk ratio of ACR20 achievement was 1.71 (95% confidence interval [CI] 1.20–2.42) for 1–2 mg/day and 2.30 (95% CI 1.79–2.96) for 3 mg/day. The risk ratio of creatinine elevation was 1.95 (95% CI 1.18–3.23) for 1–2 mg/day and 3.81 (95% CI 2.43–5.99) for 3 mg/day.

Conclusion

Tacrolimus is effective with acceptable safety in the management of RA.

Keywords:

• Conventional synthetic disease-modifying antirheumatic drug
• rheumatoid arthritis
• systematic review
• tacrolimus

Conflict of interest

YukK has received grants or speaking fees from AbbVie, Astellas, Ayumi, Bristol–Myers Squibb, Chugai, Eisai, Eli Lilly, Hisamitsu, Jansen, Kissei, Kirin, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi, and UCB. YutK has received research grants and speaking fees from Astellas Pharma Inc. MaK has nothing to be declared. TN has nothing to be declared. SH has received grants, lecture fees or speaking fees from AbbVie, Astellas Pharam, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Jansen, Kissei, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi, UCB. MiK has received honoraria from Astellas Pharam. HE has nothing to be declared. YS has nothing to be declared. HI has received a research grant and/or speaker fee from Bristol-Myers, Astellas Pharam, Kyocera, and Asahi-Kasei. KN has nothing to be declared. IM has nothing to be declared. TK has nothing to be declared. NK has nothing to be declared.KT has nothing to be declared. AI has nothing to be declared. MH has received honoraria from Astellas Pharam. NM has nothing to be declared. HY has received grant from AbbVie, Eisai, Bristol-Meyers, Novartis, Behringer, Astellas, Kaken, Nippon-Shinyaku, Pfizer, UCB, Ayumi, Ono, Daiichi-Sankyo, Taisyo-Toyama, Takeda, Tanabe-Mitsubishi, Chugai, Teijin Pharma, Torii, YLbio, and speaker honorarium from Bristol-Meyers, Pfizer, Teijin Pharma, YLbio.

Additional information

Funding

A part of this work was supported by Health and Labor Sciences Research Grants for Research on Allergic Disease and Immunology from the Ministry of Health, Labor and Welfare (grant no. H23-Meneki-Shitei-016).