Environmental Autoimmunity Group, National Institute of Environmental Health Sciences.
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health.
Semin Arthritis Rheum. 2018 Jun;47(6):858-864. doi: 10.1016/j.semarthrit.2017.10.010. Epub 2017 Oct 16.
To investigate in a pilot study the safety and efficacy of infliximab in patients with refractory dermatomyositis (DM) and polymyositis (PM).
A randomized, double-blind, placebo-controlled trial including subjects with active DM or PM. Participants had stable doses of immunosuppressive medication and prednisone (≤0.5mg/kg/day), and exhibited clinical signs of muscle weakness for at least 4 weeks prior to study entry. Participants received infusions of either placebo or infliximab 5mg/kg at 0, 2, 6, and 14 weeks in blinded manner. The primary outcome was a ≥15% manual muscle strength (MMT) improvement at week 16 compared to week 0. The secondary outcome measures were improvement defined by the International Myositis Assessment and Clinical Studies Group (IMACS) criteria. At week 16, responders in each arm had the option of either continuing the same treatment or changing to the non-responder treatment for that study arm. Non-responders in the 5mg/kg infliximab arm were increased to infliximab 7.5mg/kg for weeks 22, 30, and 38. Non-responders in the placebo arm at week 16 received infliximab 5mg/kg at weeks 16, 18, 22, 30, and 38. Outcomes were reassessed at week 40.
Twelve subjects completed the study to week 16. Six of the 12 subjects received infliximab treatment at the dose of 5mg/kg with only one subject meeting the responder criteria at that dose. Of the remaining five subjects on infliximab, three crossed over to the infliximab 7.5mg/kg dose. One of those three subjects responded. All six patients in the placebo arm crossed over to the 5mg/kg dosing regimen after week 16, and two of those responded to infliximab.
Infliximab therapy for patients with refractory PM and DM was well tolerated and may benefit a subset of patients.
在一项初步研究中探究英夫利昔单抗在难治性皮肌炎（DM）和多发性肌炎（PM）患者中的安全性和疗效。
本研究纳入了活动性 DM 或 PM 患者，为一项随机、双盲、安慰剂对照试验。患者在入组前已接受稳定剂量的免疫抑制药物和泼尼松（≤0.5mg/kg/天）治疗，且出现肌肉无力的临床症状至少 4 周。患者以盲法方式分别接受安慰剂或英夫利昔单抗 5mg/kg 输注，剂量分别为 0、2、6 和 14 周。主要终点为第 16 周与第 0 周相比，手动肌肉力量（MMT）至少改善 15%。次要终点测量指标为国际肌炎评估与临床研究组（IMACS）标准定义的改善情况。第 16 周时，每个治疗组的应答者可选择继续相同治疗或转为该研究组的非应答者治疗。5mg/kg 英夫利昔单抗组的非应答者在第 22、30 和 38 周时增加至英夫利昔单抗 7.5mg/kg。第 16 周时的非应答者在第 16、18、22、30 和 38 周时接受英夫利昔单抗 5mg/kg。第 40 周时评估结局。
12 例患者完成了第 16 周的研究。12 例患者中有 6 例接受了英夫利昔单抗 5mg/kg 剂量治疗，只有 1 例达到该剂量的应答标准。其余 5 例接受英夫利昔单抗治疗的患者中有 3 例交叉至英夫利昔单抗 7.5mg/kg 剂量。这 3 例中有 1 例应答。所有 6 例安慰剂组患者在第 16 周后交叉至英夫利昔单抗 5mg/kg 剂量方案，其中 2 例对英夫利昔单抗有应答。
英夫利昔单抗治疗难治性 PM 和 DM 患者具有良好的耐受性，可能使一部分患者受益。
