Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis

BMC Musculoskeletal Disorders

Ian CK Wong¹  Alan J Worsley¹  Celine SL Chui¹  Kenneth KC Man¹  Wallis CY Lau¹  Esther W Chan¹  Angel YS Wong¹  Ying He¹ 

[1] Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Pokfulam, Hong Kong

关键词: Meta-analysis;    Treatment outcome;    Rheumatoid arthritis;    Tofacitinib;   

Others  :  1129468
DOI  :  10.1186/1471-2474-14-298

 received in 2013-05-11, accepted in 2013-10-11,  发布年份 2013

【 摘 要 】

Background

Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which was recently approved by US Food and Drug Administration (FDA). There are several randomised clinical trials (RCTs) that have investigated the efficacy and safety of tofacitinib in adult patients with rheumatoid arthritis (RA). A systematic review with a meta-analysis of RCTs was undertaken to determine the efficacy and safety of tofacitinib in treating patients with RA.

Methods

Electronic and clinical trials register databases were searched for published RCTs of tofacitinib between 2009 and 2013. Outcomes of interest include 20% and 50% improvement in the American College of Rheumatology Scale (ACR20 and ACR50) response rates, rates of infection, the number of immunological/haematological adverse events (AEs), deranged laboratory results (hepatic, renal, haematological tests and lipoprotein level) and the incidence of drug withdrawal.

Results

Eight RCTs (n = 3,791) were reviewed. Significantly greater ACR20 response rates were observed in patients receiving tofacitinib 5 and 10 mg bid (twice daily) versus placebo at week 12, with risk ratios (RR) of 2.20 (95% CI 1.58, 3.07) and 2.38 (95% CI 1.81, 3.14) respectively. The effect was maintained at week 24 for 5 mg bid (RR 1.94; 95% CI 1.55, 2.44) and 10 mg bid (RR 2.20; 95% CI 1.76, 2.75). The ACR50 response rate was also significantly higher for patients receiving tofacitinib 5 mg bid (RR 2.91; 95% CI 2.03, 4.16) and 10 mg bid (RR 3.32; 95% CI 2.33, 4.72) compared to placebo at week 12. Patients in the tofacitinib group had significantly lower mean neutrophil counts, higher serum creatinine, higher percentage change of LDL/HDL and a higher risk of ALT/AST > 1 ULN (upper limit of normal) versus placebo. There were no significant differences in AEs and withdrawal due to AEs compared to placebo.

Conclusion

Tofacitinib is efficacious and well tolerated in patients with MTX-resistant RA up to a period of 24 weeks. However, haematological, liver function tests and lipoproteins should be monitored. Long-term efficacy and pharmacovigilance studies are recommended.

【 授权许可】

   
2013 He et al.; licensee BioMed Central Ltd.

【 图 表 】

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