TY - JOUR
T1 - Long-term safety of tofacitinib up to 9.5 years
T2 - A comprehensive integrated analysis of the rheumatoid arthritis clinical development programme
AU - Cohen, Stanley B.
AU - Tanaka, Yoshiya
AU - Mariette, Xavier
AU - Curtis, Jeffrey R.
AU - Lee, Eun Bong
AU - Nash, Peter
AU - Winthrop, Kevin L.
AU - Charles-Schoeman, Christina
AU - Wang, Lisy
AU - Chen, Connie
AU - Kwok, Kenneth
AU - Biswas, Pinaki
AU - Shapiro, Andrea
AU - Madsen, Ann
AU - Wollenhaupt, Jürgen
N1 - Funding Information:
1Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, Texas, USA 2University of Occupational and Environmental Health, Kitakyushu, Japan 3Paris-Saclay University, AP-HP, INSERM, Le Kremlin Bicêtre, France 4University of Alabama at Birmingham, Birmingham, Alabama, USA 5Seoul National University, Seoul, Korea (the Democratic People’s Republic of) 6Department of Medicine, Griffith University, Brisbane, Australia 7Oregon Health and Science University, Portland, Oregon, USA 8University of California, Los Angeles, California, USA 9Pfizer Inc, Groton, Connecticut, USA 10Pfizer Inc, New York, New York, USA 11Pfizer Inc, Peapack, New Jersey, USA 12Struenseehaus Centre for Rheumatology and Clinical Immunology, Hamburg, Germany Acknowledgements The authors would like to thank Aditya Patel (Syneos Health) and Arti Kanujia (Covance) for statistical support. Medical writing support, under the guidance of the authors, was provided by Jennifer Higginson, PhD, CMC Connect, McCann Health Medical Communications and was funded by Pfizer Inc, New York, NY, USA, in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med 2015;163:461–64).
Funding Information:
Competing interests SBC has received grant/research support from AbbVie, Amgen, Astellas, Bristol-Myers Squibb, Eli Lilly, Genentech, Gilead, Janssen, Novartis, Pfizer Inc, Roche and Sandoz; and consultancy fees from AbbVie, Amgen, Astellas, Bristol-Myers Squibb, Eli Lilly, Genentech, Gilead, Janssen, Novartis, Pfizer Inc, Roche and Sandoz. YT has received grant/research support from AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Novartis, Pfizer Inc, Sanofi and YL Biologics; and speaker fees and/or honoraria from AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Novartis, Pfizer Inc, Takeda, Teijin and YL Biologics. XM has received consultancy fees from Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Pfizer Inc, Samsung and UCB. JRC has received grant/research support from Amgen, Corrona, Crescendo Bio and Pfizer Inc; and consultancy fees from AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Eli Lilly, Janssen, Myriad, Pfizer Inc, Roche/Genentech and UCB. EBL has received consultancy fees from Pfizer Inc. PN has received grant/research support and consultancy fees from, and is part of the speakers’ bureau for, AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi and UCB. KLW has received grant/research support and consultancy fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, Pfizer Inc, Roche and UCB. CC-S has received grant/research support from AbbVie, Bristol-Myers Squibb and Pfizer Inc; and consultancy fees from Gilead, Pfizer Inc and Regeneron-Sanofi. LW, CC, KK, PB, AS and AM are employees and shareholders of Pfizer Inc. JW has received consultancy fees from, and is on the speaker’s bureau for, Pfizer Inc. Patient consent for publication All patients provided written informed consent. Ethics approval Studies were conducted in accordance with the Declaration of Helsinki and the Good Clinical Practice Guidelines, along with applicable local country regulations and laws. The study protocols were approved by the Institutional Review Boards and/or Independent Ethics Committee at each centre.
Publisher Copyright:
©
PY - 2020/10/30
Y1 - 2020/10/30
N2 - Objective 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. Methods 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. Results 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. Conclusion 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. Trial registration numbers 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, seeonline supplemental table 1.
AB - Objective 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. Methods 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. Results 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. Conclusion 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. Trial registration numbers 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, seeonline supplemental table 1.
KW - Antirheumatic Agents
KW - Arthritis
KW - Rheumatoid
KW - Therapeutics
UR - http://www.scopus.com/inward/record.url?scp=85095400914&partnerID=8YFLogxK
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U2 - 10.1136/rmdopen-2020-001395
DO - 10.1136/rmdopen-2020-001395
M3 - Article
C2 - 33127856
AN - SCOPUS:85095400914
SN - 2056-5933
VL - 6
JO - RMD Open
JF - RMD Open
IS - 3
M1 - e001395
ER -