Division of Immunology and Rheumatology, Stanford University Medical Center, Palo Alto, CA.
Regeneron Pharmaceuticals, Inc., Tarrytown, NJ.
Rheumatology (Oxford). 2018 Aug 1;57(8):1423-1431. doi: 10.1093/rheumatology/key121.
To examine 2-year safety, efficacy and radiographic outcomes of sarilumab in adults with RA and inadequate response to MTX (MTX-IR).
In the randomized, placebo-controlled MOBILITY trial, MTX-IR patients received subcutaneous sarilumab (150 or 200 mg) or placebo every 2 weeks (q2w) plus MTX for up to 1 year. Upon study completion, patients could enrol in the open-label, long-term extension study (EXTEND, NCT011046652), in which all patients received sarilumab 200 mg q2w plus MTX. Dose reduction to 150 mg q2w was allowed for abnormal laboratory findings and per investigator's discretion.
Of 1197 patients participating in MOBILITY, 901 entered EXTEND. Over the 2-year period, treatment-emergent adverse events (TEAEs) and serious AEs occurred at rates of 279.6 events per 100 patient-years and 16.6 events per 100 patient-years, respectively. The most common TEAEs were neutropenia, injection site erythema, increased alanine aminotransferase and upper respiratory tract infections. After 1 year in the open-label, long-term extension, disease activity reached similar levels regardless of initial treatment. Modified total Sharp scores at year 1 were maintained through year 2. Best radiographic outcomes were observed in patients initially randomized to sarilumab 200 mg q2w. After dose reduction, 89.4% of patients continued the study through 2 years.
Sarilumab safety through year 2 was consistent with IL-6 receptor blockade. Clinical response was similar irrespective of initial treatment, and radiographic progression stabilized. Patients initiated on sarilumab 200 mg q2w had the best radiographic outcomes. Dose reduction allowed most patients to continue with the study.
评估沙利鲁单抗治疗对甲氨蝶呤（MTX）应答不足的类风湿关节炎（RA）成年患者的 2 年安全性、疗效和影像学结局。
在这项随机、安慰剂对照的 MOBILITY 研究中，MTX-IR 患者接受皮下注射沙利鲁单抗（150 或 200mg）或安慰剂，每 2 周（q2w）1 次，同时加用 MTX，最长用药 1 年。研究结束后，患者可进入开放标签、长期扩展研究（EXTEND，NCT011046652），所有患者接受沙利鲁单抗 200mg q2w 加 MTX。根据实验室异常和研究者的判断，允许剂量减少至 150mg q2w。
在参与 MOBILITY 的 1197 例患者中，901 例进入 EXTEND。在 2 年期间，治疗出现的不良事件（TEAEs）和严重不良事件（SAEs）的发生率分别为 279.6 例/100 患者-年和 16.6 例/100 患者-年。最常见的 TEAEs 是中性粒细胞减少症、注射部位红斑、丙氨酸氨基转移酶升高和上呼吸道感染。在开放标签、长期扩展的 1 年后，无论初始治疗如何，疾病活动度均达到相似水平。1 年时改良的总Sharp 评分在第 2 年得以维持。最初随机接受沙利鲁单抗 200mg q2w 的患者观察到最佳影像学结局。剂量减少后，89.4%的患者在 2 年内继续该研究。
沙利鲁单抗在第 2 年的安全性与白细胞介素-6（IL-6）受体阻滞剂一致。临床应答与初始治疗无关，且影像学进展稳定。起始接受沙利鲁单抗 200mg q2w 的患者具有最佳的影像学结局。大多数患者允许剂量减少以继续研究。
