Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). We report the largest integrated safety analysis of tofacitinib, as of March 2017, using data from phase I, II, III, IIIb/IV and long-term extension studies in adult patients with RA.
Data were pooled for patients with RA who received ≥1 tofacitinib dose. Incidence rates (IRs; patients with events/100 patient-years [PY]; 95% CIs) of first-time occurrences were obtained for adverse events (AEs) of interest.
7061 patients received tofacitinib (total exposure: 22 875 PY; median [range] exposure: 3.1 [0 to 9.6] years). IRs (95% CI) for serious AEs, serious infections, herpes zoster (all), opportunistic infections (excluding tuberculosis [TB]) and TB were 9.0 (8.6 to 9.4), 2.5 (2.3 to 2.7), 3.6 (3.4 to 3.9), 0.4 (0.3 to 0.5) and 0.2 (0.1 to 0.2), respectively. IRs (95% CI) for malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC and lymphomas were 0.8 (0.7 to 0.9), 0.6 (0.5 to 0.7) and 0.1 (0.0 to 0.1), respectively. IRs (95% CI) for gastrointestinal perforations, deep vein thrombosis, pulmonary embolism, venous thromboembolism, arterial thromboembolism and major adverse cardiovascular events were 0.1 (0.1 to 0.2), 0.2 (0.1 to 0.2), 0.1 (0.1 to 0.2), 0.3 (0.2 to 0.3), 0.4 (0.3 to 0.5) and 0.4 (0.3 to 0.5), respectively. IR (95% CI) for mortality was 0.3 (0.2 to 0.3). IRs generally remained consistent across 6-month intervals to >78 months.
This represents the largest clinical dataset for a JAK inhibitor in RA to date. IRs remained consistent with previous reports from the tofacitinib RA clinical development programme, and stable over time.
NCT01262118; NCT01484561; NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01059864; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT00413699; NCT00661661.For summary of phase I, phase II, phase III, phase IIIb/IV and LTE studies included in the integrated safety analysis, see online supplemental table 1.
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
About The Expert
Stanley B Cohen
- Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Yoshiya Tanaka
- University of Occupational and Environmental Health, Kitakyushu, Japan.
Xavier Mariette
- Paris-Saclay University, AP-HP, INSERM, Le Kremlin Bicêtre, France.
Jeffrey R Curtis
- University of Alabama at Birmingham, Birmingham, Alabama, USA.
Eun Bong Lee
- Seoul National University, Seoul, Korea (the Democratic People’s Republic of).
Peter Nash
- Department of Medicine, Griffith University, Brisbane, Australia.
Kevin L Winthrop
- Oregon Health and Science University, Portland, Oregon, USA.
Christina Charles-Schoeman
- University of California, Los Angeles, California, USA.
Lisy Wang
- Pfizer Inc, Groton, Connecticut, USA Lisy.Wang@Pfizer.com.
Connie Chen
- Pfizer Inc, New York, New York, USA.
Kenneth Kwok
- Pfizer Inc, New York, New York, USA.
Pinaki Biswas
- Pfizer Inc, New York, New York, USA.
Andrea Shapiro
- Pfizer Inc, Peapack, New Jersey, USA.
Ann Madsen
- Pfizer Inc, New York, New York, USA.
Jürgen Wollenhaupt
- Struenseehaus Centre for Rheumatology and Clinical Immunology, Hamburg, Germany.
References
PubMed