Advances in Rheumatology (Dec 2024)

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

  • Atul Deodhar,
  • Servet Akar,
  • Jeffrey R. Curtis,
  • Bassel El-Zorkany,
  • Marina Magrey,
  • Cunshan Wang,
  • Joseph Wu,
  • Solomon B. Makgoeng,
  • Ivana Vranic,
  • Sujatha Menon,
  • Dona L. Fleishaker,
  • Annette M. Diehl,
  • Lara Fallon,
  • Arne Yndestad,
  • Robert B. M. Landewé

DOI
https://doi.org/10.1186/s42358-024-00402-x
Journal volume & issue
Vol. 64, no. 1
pp. 1 – 15

Abstract

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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).

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