在银屑病关节炎中使用静脉注射戈利木单抗抑制放射学进展：一项 III 期、随机、双盲、安慰剂对照试验的第 24 周结果。

Radiographic Progression Inhibition with Intravenous Golimumab in Psoriatic Arthritis: Week 24 Results of a Phase III, Randomized, Double-blind, Placebo-controlled Trial.

机构信息

From Internal Medicine - Rheumatology, University of California at San Diego, La Jolla, California; Department of Internal Medicine - Rheumatology, Cleveland Clinic, Cleveland, Ohio; Immunology, Janssen Research & Development LLC, Spring House, Pennsylvania; Rheumatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Drs. Harrison and Hsia, and L. Kim, K.H. Lo, and L. Noonan are employees of Janssen Research & Development LLC and own stock or stock options in Johnson & Johnson, of which Janssen Research & Development LLC is a wholly owned subsidiary.

出版信息

J Rheumatol. 2019 Jun;46(6):595-602. doi: 10.3899/jrheum.180681. Epub 2019 Feb 15.

DOI:10.3899/jrheum.180681

PMID:30770519

Abstract

OBJECTIVE

Evaluate effects of intravenous (IV) golimumab (GOL) on radiographic progression in psoriatic arthritis (PsA).

METHODS

This phase III, randomized, double-blind, placebo-controlled trial (GO-VIBRANT) randomized patients with active PsA to receive IV placebo (n = 239) or IV GOL 2 mg/kg (n = 241) at weeks 0, 4, 12, and 20. Radiographic progression (controlled secondary endpoint) was evaluated as change from baseline at Week 24 in PsA-modified total Sharp/van der Heijde scores (SvdH). The proportions of patients with a change from baseline at Week 24 in the total PsA-modified SvdH exceeding the smallest detectable change (SDC) or > 0 or 0.5 also were determined.

RESULTS

Overall, 474 patients (237/arm) contributed radiographic data. Results obtained from the 2 blinded, independent radiographic readers demonstrated good agreement (total score intraclass correlation coefficients: baseline = 0.93, Week 24 = 0.92, Week 24 change score = 0.73). GOL demonstrated significant inhibition of radiographic progression relative to placebo from baseline to Week 24 (mean changes in PsA-modified total SvdH: -0.36 vs 1.95; treatment difference: -2.32; p < 0.001). At Week 24, smaller proportions of GOL- versus placebo-treated patients demonstrated an increase in the total PsA-modified SvdH score exceeding the SDC (8.0% vs 27.0%, respectively; difference: -19.0%; p < 0.001), > 0 (28.3% vs 57.0%, respectively; difference: -28.7%; p < 0.001), or > 0.5 (18.6% vs 41.8%, respectively; difference: -23.2%; p < 0.001). Results were consistent for erosion and joint space narrowing scores, in hands and feet, and in patients with/without baseline concomitant methotrexate use. Prevention of radiographic progression by GOL was independent of clinical response.

CONCLUSION

IV GOL is significantly better than placebo in inhibiting radiographic progression of structural damage in active PsA. [Clinical trial registration number (www.ClinicalTrials.gov): NCT02181673].

摘要

目的

评估静脉注射（IV）戈利木单抗（GOL）对银屑病关节炎（PsA）影像学进展的影响。

方法

这是一项 III 期、随机、双盲、安慰剂对照试验（GO-VIBRANT），纳入了活动性 PsA 患者，随机接受 IV 安慰剂（n = 239）或 IV GOL 2 mg/kg（n = 241），分别在第 0、4、12 和 20 周给药。影像学进展（次要控制终点）评估为第 24 周时从基线开始的 PsA 改良总 Sharp/van der Heijde 评分（SvdH）的变化。还确定了从基线开始在第 24 周时总 PsA 改良 SvdH 变化超过最小可检测变化（SDC）或 > 0 或 0.5 的患者比例。

结果

总体而言，474 例患者（每组 237 例）提供了影像学数据。来自 2 位盲法、独立影像学读者的结果显示出良好的一致性（总评分组内相关系数：基线 = 0.93，第 24 周 = 0.92，第 24 周变化评分 = 0.73）。与安慰剂相比，GOL 显示出对影像学进展的显著抑制，从基线到第 24 周（PsA 改良总 SvdH 的平均变化：-0.36 与 1.95；治疗差异：-2.32；p < 0.001）。在第 24 周时，与安慰剂相比，接受 GOL 治疗的患者中，总 PsA 改良 SvdH 评分增加超过 SDC 的比例较小（分别为 8.0%和 27.0%；差异：-19.0%；p < 0.001），> 0（分别为 28.3%和 57.0%；差异：-28.7%；p < 0.001）或> 0.5（分别为 18.6%和 41.8%；差异：-23.2%；p < 0.001）。手和脚的侵蚀和关节间隙狭窄评分以及基线时同时使用甲氨蝶呤的患者和未同时使用甲氨蝶呤的患者中，结果一致。GOL 对影像学进展的抑制作用独立于临床反应。