Tofacitinib Efficacy/Safety in Patients with Ankylosing Spondylitis by Baseline Body Mass Index: A Post Hoc Analysis of Phase 2/3 Trials.

Abstract

Introduction: We assessed tofacitinib efficacy and safety in ankylosing spondylitis (AS) by body mass index (BMI) category.

Methods: Data were pooled from phase 2/3 trials; analyses included patients with active AS randomized (1:1) to tofacitinib 5 mg twice daily or placebo, who were stratified by baseline BMI into < 25, ≥ 25 to < 30, and ≥ 30 kg/m² categories. Efficacy was assessed at week 12 and safety to week 16.

Results: Of 370 patients, 153, 131, and 86 had a baseline BMI  of < 25, ≥ 25 to < 30, and ≥ 30 kg/m², respectively. At baseline, patients with BMI < 25 kg/m² were younger and more likely to be current smokers/Asian, and patients with BMI ≥ 30 kg/m² had higher mean waist circumference/swollen joint count (SJC) and were more likely to have enthesitis, high-sensitivity C-reactive protein (hsCRP) > 5 mg/L, an inadequate response to tumor necrosis factor inhibitors (TNFi), and prior biologic disease-modifying anti-rheumatic drug (bDMARD) use versus other categories. Across categories, tofacitinib responses/improvements were greater than with placebo, except for ≥ 40% Assessment of SpondyloArthritis international Society improvement (ASAS40), ASAS partial remission, 50% improvement from baseline in the Bath Ankylosing Spondylitis Disease Activity Index score (BASDAI50), and Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) inactive disease rates, which were similar for tofacitinib and placebo in the BMI ≥ 30 kg/m² category. Treatment effects were similar across categories, except for BASDAI50, which was smaller in the BMI ≥ 30 category versus  the < 25 kg/m² category. More adverse events (AEs) and serious adverse events (SAEs) with tofacitinib were reported in the BMI < 25 kg/m² category, which had a higher proportion of current smokers versus other categories.

Conclusions: Regardless of baseline BMI category, efficacy was greater with tofacitinib versus placebo in patients with AS, and no treatment effect differences between categories were observed, with exceptions for BMI ≥ 30 kg/m² (more active/treatment-refractory disease and a smaller sample size). Overall, tofacitinib safety was generally comparable across categories; however, AE/SAE rates with tofacitinib were higher in the BMI < 25 kg/m² category (which had more current smokers). This post hoc analysis demonstrates that tofacitinib can be considered as a treatment option for AS, regardless of baseline BMI category; however, interpretation was limited by small sample sizes and differences in sample sizes and baseline characteristics across categories.

Trial registration: ClinicalTrials.gov identifiers, NCT01786668 and NCT03502616.