PMID- 24139404 OWN - NLM STAT- MEDLINE DCOM- 20140924 LR - 20231110 IS - 1471-2474 (Electronic) IS - 1471-2474 (Linking) VI - 14 DP - 2013 Oct 18 TI - Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis. PG - 298 LID - 10.1186/1471-2474-14-298 [doi] AB - 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. FAU - He, Ying AU - He Y FAU - Wong, Angel Y S AU - Wong AY FAU - Chan, Esther W AU - Chan EW AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Pokfulam, Hong Kong. ewchan@hku.hk. FAU - Lau, Wallis C Y AU - Lau WC FAU - Man, Kenneth K C AU - Man KK FAU - Chui, Celine S L AU - Chui CS FAU - Worsley, Alan J AU - Worsley AJ FAU - Wong, Ian C K AU - Wong IC LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20131018 PL - England TA - BMC Musculoskelet Disord JT - BMC musculoskeletal disorders JID - 100968565 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antirheumatic Agents) RN - 0 (Piperidines) RN - 0 (Pyrimidines) RN - 0 (Pyrroles) RN - 87LA6FU830 (tofacitinib) RN - EC 2.7.10.2 (Janus Kinase 3) RN - FYS6T7F842 (Adalimumab) SB - IM MH - Adalimumab MH - Antibodies, Monoclonal, Humanized/therapeutic use MH - Antirheumatic Agents/*therapeutic use MH - Arthritis, Rheumatoid/*drug therapy MH - Humans MH - Janus Kinase 3/antagonists & inhibitors MH - Piperidines/pharmacology/*therapeutic use MH - Pyrimidines/pharmacology/*therapeutic use MH - Pyrroles/pharmacology/*therapeutic use MH - Treatment Outcome PMC - PMC3819708 EDAT- 2013/10/22 06:00 MHDA- 2014/09/25 06:00 PMCR- 2013/10/18 CRDT- 2013/10/22 06:00 PHST- 2013/05/11 00:00 [received] PHST- 2013/10/11 00:00 [accepted] PHST- 2013/10/22 06:00 [entrez] PHST- 2013/10/22 06:00 [pubmed] PHST- 2014/09/25 06:00 [medline] PHST- 2013/10/18 00:00 [pmc-release] AID - 1471-2474-14-298 [pii] AID - 10.1186/1471-2474-14-298 [doi] PST - epublish SO - BMC Musculoskelet Disord. 2013 Oct 18;14:298. doi: 10.1186/1471-2474-14-298.