You are here

  • Home
  • Archive
  • Volume 76, Issue 7
  • Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials

Article Text

Article menu
Clinical and epidemiological research
Extended report
Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials
  1. Stanley B Cohen1,
  2. Yoshiya Tanaka2,
  3. Xavier Mariette3,
  4. Jeffrey R Curtis4,
  5. Eun Bong Lee5,
  6. Peter Nash6,
  7. Kevin L Winthrop7,
  8. Christina Charles-Schoeman8,
  9. Krishan Thirunavukkarasu9,
  10. Ryan DeMasi10,
  11. Jamie Geier10,
  12. Kenneth Kwok10,
  13. Lisy Wang11,
  14. Richard Riese11,
  15. Jürgen Wollenhaupt12
  1. 1 Metroplex Clinical Research Center, Dallas, Texas, USA
  2. 2 University of Occupational and Environmental Health, Kitakyushu, Japan
  3. 3 Paris-Sud University, Le Kremlin Bicêtre, France
  4. 4 University of Alabama at Birmingham, Birmingham, Alabama, USA
  5. 5 Seoul National University, Seoul, Republic of Korea
  6. 6 University of Queensland, Queensland, Australia
  7. 7 Oregon Health and Science University, Portland, Oregon, USA
  8. 8 University of California, Los Angeles, California, USA
  9. 9 Pfizer Australia, Sydney, Australia
  10. 10 Pfizer Inc, New York, New York, USA
  11. 11 Pfizer Inc, Groton, Connecticut, USA
  12. 12 University of Hamburg, Hamburg, Germany
  1. Correspondence to Dr Ryan DeMasi; Pfizer Inc, 235 E 42nd St, New York, NY 10017, USA; Ryan.DeMasi{at}pfizer.com

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.

  • Rheumatoid Arthritis
  • Treatment
  • Cardiovascular Disease
  • Infections
  • Tuberculosis

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/annrheumdis-2016-210457

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Supplementary materials

    • Lay summary

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    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.