Norton Hillary, Sliwinska-Stanczyk Paula, Hala Tomas, El-Zorkany Bassel, Stockert Lori, Mundayat Rajiv, Wang Lisy, Ritchlin Christopher T
Inspire Sante Fe Medical Group, 2200 Brothers Road, Santa Fe, NM, 87505, USA.
Reumatika Centrum Reumatologii, Warsaw, Poland.
Rheumatol Ther. 2025 Feb;12(1):67-84. doi: 10.1007/s40744-024-00726-6. Epub 2024 Dec 5.
We assessed tofacitinib efficacy and safety in ankylosing spondylitis (AS) by body mass index (BMI) category.
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/m categories. Efficacy was assessed at week 12 and safety to week 16.
Of 370 patients, 153, 131, and 86 had a baseline BMI of < 25, ≥ 25 to < 30, and ≥ 30 kg/m, respectively. At baseline, patients with BMI < 25 kg/m were younger and more likely to be current smokers/Asian, and patients with BMI ≥ 30 kg/m 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/m category. Treatment effects were similar across categories, except for BASDAI50, which was smaller in the BMI ≥ 30 category versus the < 25 kg/m category. More adverse events (AEs) and serious adverse events (SAEs) with tofacitinib were reported in the BMI < 25 kg/m category, which had a higher proportion of current smokers versus other categories.
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/m (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/m 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.
ClinicalTrials.gov identifiers, NCT01786668 and NCT03502616.
我们按体重指数（BMI）类别评估了托法替布在强直性脊柱炎（AS）中的疗效和安全性。
汇总2/3期试验的数据；分析纳入了活动性AS患者，这些患者被随机（1:1）分配至每日两次服用5 mg托法替布或安慰剂组，并根据基线BMI分层为<25、≥25至<30以及≥30 kg/m²类别。在第12周评估疗效，在第16周评估安全性。
370例患者中，分别有153例、131例和86例患者的基线BMI<25、≥25至<30以及≥30 kg/m²。基线时，BMI<25 kg/m²的患者更年轻，更有可能是当前吸烟者/亚洲人，而BMI≥30 kg/m²的患者平均腰围/肿胀关节计数（SJC）更高，更有可能患有附着点炎、高敏C反应蛋白（hsCRP）>5 mg/L、对肿瘤坏死因子抑制剂（TNFi）反应不足以及既往使用过生物性疾病改善抗风湿药物（bDMARD）。在各BMI类别中，托法替布的反应/改善情况均优于安慰剂，但在BMI≥30 kg/m²类别中，国际脊柱关节炎协会40%改善评估（ASAS40）、ASAS部分缓解、巴斯强直性脊柱炎疾病活动指数评分（BASDAI）从基线改善50%（BASDAI50）以及使用C反应蛋白的强直性脊柱炎疾病活动评分（ASDAS-CRP）非活动疾病率方面，托法替布和安慰剂相似。除BASDAI50外，各BMI类别间的治疗效果相似，BASDAI50在BMI≥30类别中低于<25 kg/m²类别。BMI<25 kg/m²类别中报告的托法替布不良事件（AE）和严重不良事件（SAE）更多，该类别中当前吸烟者的比例高于其他类别。
无论基线BMI类别如何，托法替布治疗AS患者的疗效均优于安慰剂，且未观察到各BMI类别间的治疗效果差异，但BMI≥30 kg/m²类别除外（疾病更活跃/难治且样本量较小）。总体而言，托法替布在各BMI类别中的安全性总体相当；然而，托法替布的AE/SAE发生率在BMI<25 kg/m²类别中更高（该类别中当前吸烟者更多）。这项事后分析表明，无论基线BMI类别如何，托法替布均可被视为AS的一种治疗选择；然而，由于样本量较小以及各BMI类别间样本量和基线特征存在差异，解释受到限制。
ClinicalTrials.gov标识符，NCT01786668和NCT03502616。
