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. 2024 Dec 18;64(1):87.
doi: 10.1186/s42358-024-00402-x.

Integrated safety analysis of tofacitinib from Phase 2 and 3 trials of patients with ankylosing spondylitis

Atul Deodhar  1 , Servet Akar  2 , Jeffrey R Curtis  3 , Bassel El-Zorkany  4 , Marina Magrey  5 , Cunshan Wang  6 , Joseph Wu  6 , Solomon B Makgoeng  7 , Ivana Vranic  8 , Sujatha Menon  6 , Dona L Fleishaker  6 , Annette M Diehl  7 , Lara Fallon  9 , Arne Yndestad  10 , Robert B M Landewé  11   12
Affiliations

Integrated safety analysis of tofacitinib from Phase 2 and 3 trials of patients with ankylosing spondylitis

Atul Deodhar et al. Adv Rheumatol. .

Abstract

Objectives: Describe tofacitinib safety from an integrated analysis of randomized controlled trials (RCTs) in patients with ankylosing spondylitis (AS).

Method: Pooled data from Phase 2 (NCT01786668; 04/2013-03/2015)/Phase 3 (NCT03502616; 06/2018-08/2020) RCTs in AS patients were analyzed (3 overlapping cohorts): 16-week placebo-controlled (tofacitinib 5 mg twice daily [BID] [n = 185]; placebo [n = 187]); 48-week only-tofacitinib 5 mg BID (n = 316); 48-week all-tofacitinib (≥ 1 dose of tofacitinib 2, 5, or 10 mg BID; n = 420). Baseline 10-year atherosclerotic cardiovascular disease (ASCVD) risk was determined in patients without history of ASCVD (48-week cohorts). Adverse events (AEs)/AEs of special interest were evaluated/compared with findings from other tofacitinib programs (16 Phase 2/Phase 3 rheumatoid arthritis [RA]; 2 Phase 3 psoriatic arthritis [PsA] RCTs) and a real-world cohort of AS patients initiating biologic disease-modifying antirheumatic drugs (US MarketScan).

Results: Most patients (> 75%; 48-week cohorts) without history of ASCVD had low baseline 10-year ASCVD risk. One patient (tofacitinib 5 mg BID; in all 3 cohorts) had a serious infection (aseptic meningitis). Herpes zoster (non-serious) occurred in the 48-week only-tofacitinib 5 mg BID (n = 5 [1.6%]) and all-tofacitinib (n = 7 [1.7%]; one multi-dermatomal [tofacitinib 10 mg BID]) cohorts. No deaths, opportunistic infections, tuberculosis, malignancies, major adverse cardiovascular events, thromboembolic events, gastrointestinal perforations occurred.

Limitations: short RCT durations/low patient numbers within cohorts.

Conclusion: Tofacitinib 5 mg BID was well tolerated to 48 weeks in AS patients; safety profile was consistent with RA/PsA clinical programs and a cohort of AS patients from US routine clinical practice.

Clinical trial registration numbers: NCT01786668 (2013-02-06); NCT03502616 (2018-04-11).

Keywords: Ankylosing; Janus kinase inhibitors/adverse effects; Spondylitis; Tofacitinib.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Trials were conducted according to the Declaration of Helsinki/Good Clinical Practice Guidelines of the International Council for Harmonisation, and approved by the Institutional Review Board and/or Independent Ethics Committee of the investigational centers. Patients provided written informed consent. Consent for publication: Not applicable. Competing interests: AD has received grant/research support from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Novartis, Pfizer Inc, and UCB, and has been a consultant for AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer Inc, and UCB. SA has received grant/research support from Pfizer Inc and has been a consultant for, and participated in speaker bureaus for, AbbVie, Amgen, Eli Lilly, MSD, Novartis, Pfizer Inc, and UCB. JRC has received grant/research support from, and has been a consultant for, AbbVie, Amgen, Bristol Myers Squibb, CorEvitas, LLC (formerly Corrona, LLC), Eli Lilly, Janssen, Myriad, Novartis, Pfizer Inc, Sanofi, and UCB. BE-Z has received grant/research support from, and has been a consultant for, AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Eva, Hekma, Janssen, MSD, New Bridge, Novartis, Pfizer Inc, Roche, Sandoz, Sanofi-Aventis, and Servier. MM has received grant/research support from AbbVie, Bristol Myers Squibb, and UCB, and has been a consultant for AbbVie, Eli Lilly, Novartis, Pfizer Inc, and UCB. CW, JW, SBM, IV, SM, DLF, AMD, LF, and AY are employees and stockholders of Pfizer Inc. RBML has been a consultant for AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos NV, Gilead Sciences, Janssen, Novartis, Pfizer Inc, and UCB.

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