Efficacy and Safety of Tofacitinib in Patients with Psoriatic Arthritis or Ankylosing Spondylitis by Cigarette Smoking Status

Abstract

Introduction: Routine care studies of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) demonstrated attenuated responses to tumor necrosis factor inhibitors in current/past versus never smokers. This post hoc analysis assessed tofacitinib efficacy and safety in patients with PsA or AS by cigarette smoking status at trial screening.

Methods: Pooled data from phase 3 and long-term extension (safety only) PsA trials and phase 2 and 3 AS trials were assessed by current/past versus never smoker status. Analysis included efficacy and safety data for tofacitinib 5 (PsA/AS) and 10 (PsA only) mg twice daily (BID) or placebo, and safety data in AS for tofacitinib 2 and 10 mg BID. Efficacy outcomes included American College of Rheumatology ≥ 50% responses (ACR50) and minimal disease activity (MDA) responses to month (M)6/M3 (tofacitinib/placebo) in PsA; and ≥ 40% improvement in Assessment of SpondyloArthritis international Society responses (ASAS40) and AS Disease Activity Score (ASDAS) < 2.1 responses to week (W)16 in AS. Safety was assessed to M48/W48 (PsA/AS), adjusted for treatment/smoking status/median body mass index (BMI) status/sex/trial/treatment-smoking status interaction.

Results: PsA/AS cohorts included 342/178 current/past and 572/194 never smokers. Tofacitinib efficacy was generally greater versus placebo to M3/W6 (PsA/AS), and comparable in current/past and never smokers to M6/W16 (PsA/AS). In patients receiving ≥ 1 tofacitinib dose, adjusted treatment-emergent adverse event (TEAE)/serious AE (SAE)/discontinuation due to AE incidence rates (IRs) to M48 in PsA were higher in current/past versus never smokers; adjusted IRs to W48 in AS were higher in current/past versus never smokers for TEAEs, but similar for SAEs/discontinuation due to AEs.

Conclusions: In both patients with PsA and AS, tofacitinib efficacy was greater versus placebo, and comparable across smoking categories. Adjusted IRs were higher in current/past versus never smokers for TEAEs, SAEs, discontinuation due to AEs in PsA, and for TEAEs in AS, complementing reports of associations between smoking and comorbidities in spondyloarthritis. Findings support increased surveillance/caution for patients with PsA or AS with smoking history.

Trial registration: ClinicalTrials.gov: NCT01877668/NCT01882439/NCT03486457/NCT01976364/NCT01786668/NCT03502616.

Keywords: Ankylosing spondylitis; Inflammation; Interventional studies; JAK inhibitors; Psoriatic arthritis; Smoking; Spondyloarthritis; Tofacitinib.

Fig. 1

Efficacy outcomes in PsA and AS by current/past and never smoker status at trial screening. ACR20 response, HAQ-DI, and ASAS20 response (primary outcomes from the pivotal trials) are described in the electronic supplementary material (Supplementary Fig. 1). *p < 0.05 for current/past versus never smokers. ^aDue to the presence of zero rates, baseline values were omitted to improve the model fit. ^b1 and 3 never smokers who received tofacitinib 10 mg BID and placebo, respectively, had minimal disease activity at baseline. ^c1 current/past and 1 never smoker who received tofacitinib 5 mg BID had baseline ASDAS < 2.1. ACR20/50 American College of Rheumatology ≥ 20%/ ≥ 50% response, AS ankylosing spondylitis, ASAS20/40 ≥ 20/ ≥ 40% improvement in Assessment of SpondyloArthritis international Society, ASDAS Ankylosing Spondylitis Disease Activity Score, BID twice daily, CI confidence interval, HAQ-DI Health Assessment Questionnaire-Disability Index, MDA minimal disease activity, n number of patients with response, N number of evaluable patients, OR odds ratio, PsA psoriatic arthritis, SE standard error