托法替布治疗类风湿关节炎患者的疗效与基线体重指数分层：来自 3 期研究的汇总数据分析。
Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by baseline body mass index: an analysis of pooled data from phase 3 studies.
机构信息
Cabrillo Center for Rheumatic Disease, San Diego, California, USA.
Section of Rheumatology, Hospital Universitario Marques de Valdecilla, Santander, Spain.
出版信息
RMD Open. 2022 May;8(1). doi: 10.1136/rmdopen-2021-002103.
OBJECTIVE
Tofacitinib is an oral Janus kinase for the treatment of rheumatoid arthritis (RA). This post hoc analysis assessed whether baseline body mass index (BMI) impacts tofacitinib efficacy in patients with RA.
METHODS
Pooled data from six phase 3 studies in patients receiving tofacitinib 5 mg (N=1589) or 10 mg (N=1611) twice daily or placebo (advancing to active treatment at months 3 or 6; N=680), ±conventional synthetic disease-modifying antirheumatic drugs, were stratified by baseline BMI (<25, 25 to <30, ≥30 kg/m). Endpoints (through to month 6) were assessed descriptively: American College of Rheumatology 20/50/70 response rates; changes from baseline (∆) in Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4(ESR)), DAS28-4(C-reactive protein), Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire-Disability Index (HAQ-DI) and pain; and proportions of patients achieving DAS28-4(ESR) ≥1.2 and HAQ-DI ≥0.22 decreases from baseline, low disease activity (DAS28-4(ESR) ≤3.2 or CDAI ≤10) and radiographic non-progression (Δmodified Total Sharp Score ≤0.5; months 12 and 24). Estimates were adjusted using multivariable models for selected outcomes. Univariate/multivariable regression analyses determined predictors of month 6 outcomes.
RESULTS
Of 3880 patients included, 1690 (43.6%), 1173 (30.2%) and 1017 (26.2%) had baseline BMI <25, 25 to <30 and ≥30 kg/m, respectively. Tofacitinib showed greater efficacy improvements versus placebo in each BMI category. Differences in efficacy outcomes (adjusted and unadjusted) were generally not clinically meaningful across BMI categories within treatment groups. In regression analyses, BMI was not consistently associated with selected outcomes.
CONCLUSIONS
Baseline BMI did not consistently affect tofacitinib response suggesting that tofacitinib is an effective oral treatment option for adults with moderate to severe RA regardless of baseline BMI, including patients with BMI ≥30 kg/m.
TRIAL REGISTRATION NUMBERS
NCT00814307, NCT01039688; NCT00960440; NCT00847613; NCT00856544; NCT00853385.
目的
托法替布是一种用于治疗类风湿关节炎（RA）的口服 Janus 激酶抑制剂。本事后分析评估了基线身体质量指数（BMI）是否影响 RA 患者托法替布的疗效。
方法
6 项接受托法替布 5mg（N=1589）或 10mg（N=1611）每日 2 次或安慰剂（在第 3 或 6 个月时转为活性治疗；N=680）治疗的患者的 3 期研究的汇总数据，±常规合成改善病情的抗风湿药物，按基线 BMI（<25、25-<30、≥30kg/m）分层。终点（至第 6 个月）通过描述性评估进行评估：美国风湿病学会 20/50/70 反应率；从基线（∆）变化疾病活动评分 28 关节、红细胞沉降率（DAS28-4（ESR））、DAS28-4（C-反应蛋白）、临床疾病活动指数（CDAI）、健康评估问卷残疾指数（HAQ-DI）和疼痛；以及从基线降低 DAS28-4（ESR）≥1.2 和 HAQ-DI≥0.22 的患者比例，疾病活动低（DAS28-4（ESR）≤3.2 或 CDAI≤10）和放射学非进展（Δ改良总Sharp 评分≤0.5；第 12 个月和第 24 个月）。使用多变量模型对选定的结局进行调整估计。单变量/多变量回归分析确定了第 6 个月结局的预测因素。
结果
在纳入的 3880 名患者中，分别有 1690（43.6%）、1173（30.2%）和 1017（26.2%）名患者的基线 BMI<25、25-<30 和≥30kg/m。与安慰剂相比，托法替布在每个 BMI 类别中均显示出更大的疗效改善。在治疗组内，BMI 类别内的疗效结局（调整后和未调整）差异通常无临床意义。在回归分析中，BMI 与某些结局并不始终相关。
结论
基线 BMI 并不始终影响托法替布的反应，这表明托法替布是一种有效的口服治疗选择，适用于中度至重度 RA 的成年人，无论基线 BMI 如何，包括 BMI≥30kg/m 的患者。
临床试验注册号
NCT00814307、NCT01039688；NCT00960440；NCT00847613；NCT00856544；NCT00853385。
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