Charité - University Medicine Berlin, Berlin, Germany.
University of Glasgow, Glasgow, UK.
Arthritis Rheumatol. 2018 May;70(5):679-689. doi: 10.1002/art.40420. Epub 2018 Mar 31.
Mavrilimumab, a human monoclonal antibody, targets granulocyte-macrophage colony-stimulating factor receptor α. We undertook to determine the long-term safety and efficacy of mavrilimumab in rheumatoid arthritis patients in 2 phase IIb studies (1071 and 1107) and in 1 open-label extension study (ClinicalTrials.gov identifier: NCT01712399).
In study 1071, patients with an inadequate response to disease-modifying antirheumatic drugs (DMARDs) received mavrilimumab (30, 100, or 150 mg) or placebo every other week plus methotrexate. In study 1107, patients with an inadequate response to anti-tumor necrosis factor agents and/or DMARDs received 100 mg mavrilimumab every other week or 50 mg golimumab every 4 weeks plus methotrexate. Patients entering the open-label extension study received 100 mg mavrilimumab every other week plus methotrexate. Long-term safety and efficacy of mavrilimumab were assessed.
A total of 442 patients received mavrilimumab (14 of 245 patients from study 1071, 9 of 70 patients from study 1107, and 52 of 397 patients from the open-label extension study discontinued mavrilimumab treatment throughout the studies). The cumulative safety exposure was 899 patient-years; the median duration of mavrilimumab treatment was 2.5 years (range 0.1-3.3 years). The most common treatment-emergent adverse events (AEs) were nasopharyngitis (n = 69; 7.68 per 100 patient-years) and bronchitis (n = 51; 5.68 per 100 patient-years). At weeks 74 and 104, 3.5% and 6.2% of patients, respectively, demonstrated reduction in forced expiratory volume in 1 second, while 2.9% and 3.4% of patients, respectively, demonstrated reduction in forced vital capacity (>20% reduction from baseline to <80% predicted). Most pulmonary changes were transient and only infrequently associated with AEs. Mavrilimumab at 100 mg every other week demonstrated sustained efficacy; at week 122, 65.0% of patients achieved a Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) of <3.2, and 40.6% of patients achieved a DAS28-CRP of <2.6.
Long-term treatment with mavrilimumab maintained response and was well-tolerated with no increased incidence of treatment-emergent AEs. Safety data were comparable with those from both phase IIb qualifying studies.
Mavrilimumab 是一种靶向粒细胞-巨噬细胞集落刺激因子受体 α 的人源单克隆抗体。我们进行了两项 IIb 期研究（1071 与 1107）和一项开放标签扩展研究（临床试验.gov 标识符：NCT01712399），以确定 mavrilimumab 在类风湿关节炎患者中的长期安全性和疗效。
在 1071 研究中，对疾病修饰抗风湿药物（DMARDs）治疗应答不足的患者给予 mavrilimumab（30、100 或 150mg）或安慰剂，每 2 周 1 次，同时给予甲氨蝶呤。在 1107 研究中，对肿瘤坏死因子拮抗剂和/或 DMARDs 治疗应答不足的患者给予 100mg mavrilimumab 每 2 周 1 次或 50mg 戈利木单抗每 4 周 1 次，同时给予甲氨蝶呤。进入开放标签扩展研究的患者给予 100mg mavrilimumab 每 2 周 1 次，同时给予甲氨蝶呤。评估 mavrilimumab 的长期安全性和疗效。
共有 442 名患者接受了 mavrilimumab 治疗（来自 1071 研究的 245 名患者中有 14 名，来自 1107 研究的 70 名患者中有 9 名，来自开放标签扩展研究的 397 名患者中有 52 名在整个研究中停止了 mavrilimumab 治疗）。累积安全性暴露时间为 899 患者-年；mavrilimumab 的中位治疗时间为 2.5 年（范围 0.1-3.3 年）。最常见的治疗期不良事件（AE）是鼻咽炎（n=69；每 100 患者-年 7.68 例）和支气管炎（n=51；每 100 患者-年 5.68 例）。在第 74 周和第 104 周时，分别有 3.5%和 6.2%的患者出现 1 秒用力呼气容积（FEV1）下降，分别有 2.9%和 3.4%的患者出现用力肺活量（FVC）下降（与基线相比下降>20%，<80%预测值）。大多数肺部变化是短暂的，且仅偶尔与 AE 相关。每隔一周给予 100mg mavrilimumab 可保持疗效；在第 122 周时，65.0%的患者达到了 C 反应蛋白水平（DAS28-CRP）<3.2 的 28 个关节疾病活动度（DAS28-CRP）缓解，40.6%的患者达到了 DAS28-CRP<2.6 的缓解。
长期使用 mavrilimumab 维持了缓解，且耐受性良好，治疗期新发 AE 发生率未增加。安全性数据与两项 IIb 期资格研究相似。
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