法国布雷斯特大学医院Alain Saraux团队研究了托珠单抗对接受糖皮质激素治疗的活动性风湿性多肌痛患者疾病活动性的影响。2022年9月20日，《美国医学会杂志》发表了这一研究成果。

对于糖皮质激素依赖性风湿性多肌痛患者，几乎没有可用的治疗方法。IL-6拮抗剂可降低活动性糖皮质激素依赖性风湿性多肌痛患者的疾病活动性。该研究旨在比较托珠单抗与安慰剂治疗糖皮质激素依赖性风湿性多肌痛的疗效。

这项双盲、平行组、安慰剂对照的随机临床试验于2017年2月至2019年10月在法国17家医院进行，共招募了101名风湿性多肌痛患者。最终随访于2020年11月进行。纳入标准为持续性疾病活动（使用C-反应蛋白水平[CRP-PMR-AS]>10计算的风湿性多肌痛活动评分）和每天大于或等于10毫克的泼尼松剂量。患者被随机分配，分别接受静脉注射托珠单抗（8 mg/kg； 51例）或安慰剂（50例）治疗，每4周一次，持续24周，并结合预先规定的标准减量口服泼尼松。

主要疗效终点为CRP PMR-AS小于10（范围为0-100；数值越高，表明活动性越强；没有定义最小临床重要差异），同时泼尼松剂量小于或等于每天5毫克，或与基线相比，第24周时泼尼松剂量减少大于或等于10毫克。研究组在第24周时评估了11项次要结局，包括疾病活动度（用CRP PMR-AS测量）和不再服用泼尼松的患者比例。

在101名随机患者中（平均年龄为67.2岁；68[67.3%]名为女性），100名（99%）患者至少接受了1次输液，100名患者完成了试验。托珠单抗组中有67.3%的患者达到了主要终点，安慰剂组中有31.4%的患者，校正后的相对风险为2.3，组间差异显著。

在24周时11个报告的次要终点中，有7个显示出有利于服用托珠单抗的显著差异，包括CRP PMR-AS平均得分（分别为7.5分与14.9分）和不再接受泼尼松治疗的患者百分比（分别为49.0%与19.6%）。最常见的不良事件是感染，托珠单抗组有23名患者（46.9%）发生，安慰剂组有20名患者（39.2%）发生。

研究结果表明，对于接受泼尼松治疗的活动性风湿性多肌痛患者，与安慰剂相比，在第24周，托珠单抗导致CRP PMR-AS低于10且强的松需求量减少的患者比例显著增加。

附：原文原文

Title: Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial

Author: Valérie Devauchelle-Pensec, Guillermo Carvajal-Alegria, Emmanuelle Dernis, Christophe Richez, Marie-Elise Truchetet, Daniel Wendling, Eric Toussirot, Aleth Perdriger, Jacques-Eric Gottenberg, Renaud Felten, Bruno Jean Fautrel, Laurent Chiche, Pascal Hilliquin, Catherine Le Henaff, Benjamin Dervieux, Guillaume Direz, Isabelle Chary-Valckenaere, Divi Cornec, Dewi Guellec, Thierry Marhadour, Emmanuel Nowak, Alain Saraux

Issue&Volume: 2022/09/20

Abstract:

Importance  Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active glucocorticoid-dependent polymyalgia rheumatica.

Objective  To compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica.

Design, Setting, and Participants  This double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level [CRP PMR-AS] >10) and prednisone dose greater than or equal to 10 mg per day.

Interventions  Patients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n=51) or placebo (n=50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone.

Main Outcomes and Measures  The primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone.

Results  Of the 101 randomized patients (mean age, 67.2 years; 68 [67.3%] women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% [95% CI, 19.4%-52.6%]; adjusted relative risk, 2.3 [95% CI, 1.5-3.6]; P<.001). Of 11 reported secondary end points at 24 weeks, 7 showed significant differences favoring tocilizumab, including mean CRP PMR-AS score (7.5 [95% CI, 5.4-9.6] vs 14.9 [95% CI, 11.4-18.4]; adjusted difference, 7.5 [95% CI, 11.2 to 3.8]; P<.001) and the percentage of patients no longer receiving prednisone (49.0% vs 19.6%; adjusted difference, 29.3% [95% CI, 18.9%-39.7%]; adjusted relative risk, 2.5 [95% CI, 1.8-3.5]; P<.001). The most frequent adverse events were infections, experienced by 23 patients (46.9%) in the tocilizumab group and 20 (39.2%) in the placebo group.

Conclusions and Relevance  Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms.

DOI: 10.1001/jama.2022.15459

Source: https://jamanetwork.com/journals/jama/article-abstract/2796378