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Safety and maintenance of response for tofacitinib monotherapy and combination therapy in rheumatoid arthritis: an analysis of pooled data from open-label long-term extension studies
  1. Roy Fleischmann1,
  2. Jürgen Wollenhaupt2,
  3. Liza Takiya3,
  4. Anna Maniccia4,
  5. Kenneth Kwok4,
  6. Lisy Wang5 and
  7. Ronald F van Vollenhoven6
  1. 1 Metroplex Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
  2. 2 Schoen-Klinik Hamburg-Eilbek Teaching Hospital, University of Hamburg, Hamburg, Germany
  3. 3 Pfizer Inc, Collegeville, Pennsylvania, USA
  4. 4 Pfizer Inc, New York City, New York, USA
  5. 5 Pfizer Inc, Groton, Connecticut, USA
  6. 6 Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands
  1. Correspondence to Dr Liza Takiya; liza.takiya{at}


Objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. This post hoc analysis evaluated patients receiving tofacitinib monotherapy or combination therapy, as well as those who switched from monotherapy to combination therapy (mono→combo) or vice versa (combo→mono) in long-term extension (LTE) studies.

Methods Data were pooled from open-label LTE studies (ORAL Sequel (NCT00413699; ongoing; data collected 14 January 2016) and NCT00661661) involving patients who participated in qualifying index studies. Efficacy outcomes included American College of Rheumatology 20/50/70 rates, change from baseline in Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4(ESR)), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index and DAS28-4(ESR) and CDAI low disease activity and remission. Safety was evaluated over 96 months.

Results Of the 4967 patients treated, 35.4% initiated tofacitinib monotherapy, 64.6% initiated combination therapy, 2.6% were mono→combo switchers and 7.1% were combo→mono switchers. Patients who switched multiple times were excluded. Of those who initiated monotherapy and combination therapy, 87.8% (1543/1757) and 82.0% (2631/3210), respectively, remained on the same regimen throughout the study; efficacy was maintained. Incidence rates (IRs) for serious adverse events with tofacitinib 5 mg and 10 mg twice daily, respectively, were 9.42 and 8.41 with monotherapy and 8.36 and 10.75 with combination therapy; IRs for discontinuations due to AEs were 7.13 and 6.06 with monotherapy and 7.82 and 8.06 with combination therapy (overlapping CIs). For mono→combo and combo→mono switchers, discontinuations due to AEs were experienced by 0.8% and 0.9%, respectively, within 30 days of switching.

Conclusion Tofacitinib efficacy as monotherapy or combination therapy was maintained through month 48 and sustained to month 72, with minimal switching of treatment regimens. Safety was consistent over 96 months.

Clinical trial registration NCT00413699 (Pre-results) and NCT00661661 (Results).

  • rheumatoid arthritis
  • disease activity
  • treatment

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  • Contributors All authors contributed to the interpretation of study results, critical revision of the article and final approval of the version to be published. In addition, RF, JW and RFvV were involved in the acquisition of data. LT, AM, KK and LW were also involved in the conception or design of the study and the analysis of the data.

  • Funding This work was supported by Pfizer Inc.

  • Competing interests RF has received grant/research support from Pfizer Inc and is a consultant for Pfizer Inc. JW is a consultant for Pfizer Inc and is a member of the speaker’s bureau for Pfizer Inc. RFvV has received grant/research support from Pfizer Inc and is a consultant for Pfizer Inc. LW, AM, KK and LT are employees and shareholders of Pfizer Inc.

  • Ethics approval The studies were approved by the Institutional Review Boards and/or Independent Ethics Committees at each investigational centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.

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