Article Text
Abstract
Objectives Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We report an integrated safety summary of tofacitinib from two phase I, nine phase II, six phase III and two long-term extension studies in adult patients with active RA.
Methods Data were pooled for all tofacitinib-treated patients (data cut-off: 31 March 2015). Incidence rates (IRs; patients with event/100 patient-years) and 95% CIs are reported for adverse events (AEs) of interest.
Results 6194 patients received tofacitinib for a total 19 406 patient-years' exposure; median exposure was 3.4 patient-years. IR (95% CI) for serious AEs was 9.4 (9.0 to 9.9); IR for serious infections was 2.7 (2.5 to 3.0). IR for (all) herpes zoster was 3.9 (3.6 to 4.2); IR for disseminated or multidermatomal herpes zoster was 0.3 (0.2 to 0.4). IR for opportunistic infections (excluding tuberculosis) was 0.3 (0.2 to 0.4) and was 0.2 (0.1 to 0.3) for tuberculosis. IR for malignancies (excluding non-melanoma skin cancer (NMSC)) was 0.9 (0.8 to 1.0); NMSC IR was 0.6 (0.5 to 0.7). IR for gastrointestinal perforations was 0.1 (0.1 to 0.2). Analysis of IR for serious infections, herpes zoster and malignancies by 6-month intervals did not reveal any notable increase in IR with longer-duration tofacitinib exposure.
Conclusion This analysis of tofacitinib exposure up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. AEs were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports.
Trial registration numbers NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT00413699, NCT00661661; Results.
- Rheumatoid Arthritis
- Treatment
- Cardiovascular Disease
- Infections
- Tuberculosis
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Footnotes
Handling editor Tore K Kvien
Contributors SBC made substantial contributions to the study conception and design and analysis and interpretation of the data; was involved in drafting the article and revising it critically for important intellectual content; and approved the final version to be published. YT, JRC, KK and RR made substantial contributions to the study conception and design, acquisition of data, and analysis and interpretation of the data; were involved in drafting the article and revising it critically for important intellectual content; and approved the final version to be published. XM made substantial contributions to the analysis and interpretation of the data; was involved in drafting the article and revising it critically for important intellectual content; and approved the final version to be published. EBL, CC-S, LW and JW made substantial contributions to acquisition of data and analysis and interpretation of the data; were involved in drafting the article and revising it critically for important intellectual content; and approved the final version to be published. PN made substantial contributions to acquisition of data; was involved in drafting the article and revising it critically for important intellectual content; and approved the final version to be published. KLW, KT, RDM and JG made substantial contributions to the analysis and interpretation of the data; were involved in drafting the article and revising it critically for important intellectual content; and approved the final version to be published.
Funding This study was sponsored by Pfizer Inc.
Competing interests SBC, KLW, CC-S and JW have served as consultants for, and have received speaker fees and honoraria from, Pfizer Inc. YT has served as a consultant for, and has received speaker fees and honoraria from, AbbVie, Asahi-kasei, Astellas Pharma, BMS, Chugai Pharma, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe, Pfizer Inc, Sanofi, Takeda, Teijin and YL Biologics. XM has served as a consultant for, and has received speaker fees and honoraria from, BMS, GlaxoSmithKline, Pfizer Inc and UCB. EBL has served as a consultant for Pfizer Inc. KT, RDM, JG, KK and LW are employees and shareholders of Pfizer Inc. RR was an employee of Pfizer Inc at the time these analyses were conducted and holds stock/stock options in Pfizer Inc.
Patient consent Obtained.
Ethics approval Multiple Ethics Committees/Institutional Review Boards approved the studies. Additional details available upon request.
Provenance and peer review Not commissioned; externally peer reviewed.