Effect of Filgotinib on Body Mass Index (BMI) and Effect of Baseline BMI on the Efficacy and Safety of Filgotinib in Rheumatoid Arthritis,Rheumatology and Therapy

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Effect of Filgotinib on Body Mass Index (BMI) and Effect of Baseline BMI on the Efficacy and Safety of Filgotinib in Rheumatoid Arthritis
Rheumatology and Therapy ( IF 2.9 ) Pub Date : 2023-09-25 , DOI: 10.1007/s40744-023-00599-1
Alejandro Balsa ₁ , Siegfried Wassenberg ₂ , Yoshiya Tanaka ₃ , Anne Tournadre ₄ , Hans-Dieter Orzechowski ₅ , Vijay Rajendran ₆ , Udo Lendl ₅ , Pieter-Jan Stiers ₇ , Chris Watson ₈ , Roberto Caporali ₉ , James Galloway ₁₀ , Patrick Verschueren ₁₁

Affiliation

Rheumatology Service, Hospital La Paz Institute for Health Research (IdiPAZ), Universidad Autónoma de Madrid, Paseo de la Castellana 261, 28046, Madrid, Spain.
Department of Rheumatology, Rheumazentrum Ratingen, Ratingen, Germany.
The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Japan.
Rheumatology Service, Clermont Ferrand University Hospital, Clermont-Ferrand, France.
Medical Affairs, Galapagos Biopharma Deutschland GmbH, Munich, Germany.
Clinical Research, Galapagos NV, Mechelen, Belgium.
Biostatistics, Galapagos NV, Mechelen, Belgium.
Medical Affairs, Galapagos Biotech Ltd, Cambridge, UK.
Department of Clinical Sciences and Community Health, The University of Milan and ASST G. Pini-CTO Hospital, Milan, Italy.
Centre for Rheumatic Diseases, King's College London, London, UK.
Department of Rheumatology, University Hospital Leuven, Leuven, Belgium.

Introduction

This post hoc analysis of the phase 3 rheumatoid arthritis (RA) filgotinib clinical trial program assessed the effect of filgotinib on body mass index (BMI) in patients with RA and the impact of BMI on the efficacy and safety of filgotinib.

Methods

FINCH 1–3 were randomized, double-blind, active- or placebo-controlled phase 3 trials of filgotinib 100 and 200 mg in patients with RA (N = 3452). BMI assessments included the mean change from baseline in BMI and the proportion of patients whose BMI increased by incremental thresholds. Efficacy measures included American College of Rheumatology (ACR) 20/50/70 response and low disease activity/remission according to Disease Activity Score 28 using C-reactive protein. The exposure-adjusted incident rate (EAIR) of adverse events (AEs) was assessed by baseline BMI, using integrated data from the FINCH 1–4 and the phase 2 DARWIN 1–3 studies (total filgotinib exposure = 8085 patient-years).

Results

Mean change from baseline in BMI over time was similar across treatment arms. In most patients, BMI increased by ≤ 1 or 2 kg/m² at both weeks 12 and 24, regardless of treatment group or baseline BMI; few patients had increases of ≥ 4 kg/m². For most efficacy measures, filgotinib 200 mg was more efficacious than filgotinib 100 mg or active comparators or placebo across BMI subgroups. For the higher filgotinib dose, the EAIR of serious treatment-emergent AEs, venous thrombotic and embolic events, and major adverse cardiovascular events increased with increasing BMI.

Conclusions

Filgotinib did not lead to substantial changes in BMI, and BMI did not appear to affect the efficacy of filgotinib.

Trial Registration

ClinicalTrials.gov identifiers: NCT02889796, NCT02873936, NCT02886728, NCT03025308, NCT01888874, NCT01894516, NCT02065700.

中文翻译：

Filgotinib 对体重指数 (BMI) 的影响以及基线 BMI 对 Filgotinib 治疗类风湿关节炎疗效和安全性的影响

介绍

这项对 3 期类风湿性关节炎 (RA) filgotinib 临床试验计划的事后分析评估了 filgotinib 对 RA 患者体重指数 (BMI) 的影响以及 BMI 对 filgotinib 疗效和安全性的影响。

方法

FINCH 1-3 是 RA 患者接受 filgotinib 100 和 200 mg 治疗的随机、双盲、活性或安慰剂对照 3 期试验（ N = 3452）。 BMI 评估包括 BMI 相对于基线的平均变化以及 BMI 按增量阈值增加的患者比例。功效测量包括美国风湿病学会 (ACR) 20/50/70 反应以及根据使用 C 反应蛋白的疾病活动评分 28 得出的低疾病活动/缓解。使用 FINCH 1-4 和 2 期 DARWIN 1-3 研究的综合数据（总 filgotinib 暴露 = 8085 患者年），通过基线 BMI 评估不良事件 (AE) 的暴露调整发生率 (EAIR)。

结果

随着时间的推移，不同治疗组的 BMI 相对于基线的平均变化相似。在大多数患者中，无论治疗组或基线 BMI 为何，BMI 在第 12 周和第 24 周均增加 ≤ 1 或 2 kg/m ² ；少数患者体重增加≥4 kg/m ² 。对于大多数疗效指标，在 BMI 亚组中，filgotinib 200 mg 比 filgotinib 100 mg 或活性比较药物或安慰剂更有效。对于较高剂量的filgotinib，严重治疗中出现的AE、静脉血栓和栓塞事件以及主要不良心血管事件的EAIR随着BMI的增加而增加。