Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme
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...
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BMJ Publishing Group
2020-10-01
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| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/6/3/e001395.full |
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| author | Peter Nash Yoshiya Tanaka Kevin L Winthrop Eun Bong Lee Xavier Mariette Jeffrey R Curtis Kenneth Kwok Connie Chen Pinaki Biswas Lisy Wang Christina Charles-Schoeman Ann Madsen Stanley B Cohen Andrea Shapiro Jürgen Wollenhaupt |
| author_facet | Peter Nash Yoshiya Tanaka Kevin L Winthrop Eun Bong Lee Xavier Mariette Jeffrey R Curtis Kenneth Kwok Connie Chen Pinaki Biswas Lisy Wang Christina Charles-Schoeman Ann Madsen Stanley B Cohen Andrea Shapiro Jürgen Wollenhaupt |
| author_sort | Peter Nash |
| collection | DOAJ |
| description | 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, see online supplemental table 1. |
| format | Article |
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| institution | Kabale University |
| issn | 2056-5933 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
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| series | RMD Open |
| spelling | doaj-art-06d315c88fb8416d89479fa698afb87f2025-02-10T03:00:12ZengBMJ Publishing GroupRMD Open2056-59332020-10-016310.1136/rmdopen-2020-001395Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programmePeter Nash0Yoshiya Tanaka1Kevin L Winthrop2Eun Bong Lee3Xavier Mariette4Jeffrey R Curtis5Kenneth Kwok6Connie Chen7Pinaki Biswas8Lisy Wang9Christina Charles-Schoeman10Ann Madsen11Stanley B Cohen12Andrea Shapiro13Jürgen Wollenhaupt14School of Medicine, Griffith University, Brisbane, Queensland, AustraliaThe First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu City, Japan7 Oregon Health and Science University, Portland, Oregon, USA2 Internal Medicine, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)3 Paris-Saclay University, AP-HP, INSERM, Le Kremlin Bicêtre, FranceUniversity of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, USA11 Pfizer Inc, New York, New York, USA4Pfizer Inc, New York, NY, United States of America10 Pfizer Inc, New York, New York, USA9 Pfizer Inc, Groton, Connecticut, USA3 Division of Rheumatology, Department of Medicine, University of California Los Angeles, Los Angeles, California, USA4Pfizer Inc, New York, NY, United States of America1 Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, Texas, USA9Pfizer Inc, Peapack, NJ, United States of America2Schön-Klinik Hamburg-Eilbek Teaching Hospital of the University of Hamburg, Hamburg, GermanyObjective 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, see online supplemental table 1.https://rmdopen.bmj.com/content/6/3/e001395.full |
| spellingShingle | Peter Nash Yoshiya Tanaka Kevin L Winthrop Eun Bong Lee Xavier Mariette Jeffrey R Curtis Kenneth Kwok Connie Chen Pinaki Biswas Lisy Wang Christina Charles-Schoeman Ann Madsen Stanley B Cohen Andrea Shapiro Jürgen Wollenhaupt Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme RMD Open |
| title | Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme |
| title_full | Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme |
| title_fullStr | Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme |
| title_full_unstemmed | Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme |
| title_short | Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme |
| title_sort | long term safety of tofacitinib up to 9 5 years a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme |
| url | https://rmdopen.bmj.com/content/6/3/e001395.full |
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