前沿進展丨利妥昔單抗對難治性多肌炎和皮肌炎有效，而與使用的早晚無關(guān)

明月晴天1964 2017-05-19

展開全文

作者：CV Oddis,et al.

翻譯：北醫(yī)三院王文季

發(fā)布：孫琳審核：劉暢

摘要

目的:為評估利妥昔單抗對成人和兒童肌炎病人的安全性和有效性而進行的一項隨機雙盲安慰劑對照試驗。

方法:以難治性成人和青少年皮肌炎病人及成人難治性多肌炎病人為納入對象，納入標(biāo)準包括成人肌無力和≥2項其他的核心組異常值，青少年皮肌炎要求≥3項核心組異常值，伴或不伴有肌無力。病人隨機分為早期或晚期接收利妥昔單抗治療組，納入研究后可以接受激素及免疫抑制劑治療，兩組主要終點時間為達到國際肌炎評估和臨床研究小組初步定義的獲得改善時間（DOI）。次要終點為達到肌肉力量提高20%并且20%早期或晚期接收利妥昔單抗治療組病人第8周獲得改善。

結(jié)果: 在200名隨機分配的病人中（包括76名多肌炎，76名皮肌炎，48名青少年皮肌炎患者），晚期（n=102）或早期（n=93）接收利妥昔單抗治療2組中（P=0.74，log檢驗）195名病人達到獲得改善的時間無明顯差別，獲得改善的中位時間分別為20.2周和20.0。次要終點在兩組病人中也沒有顯著差異。通過44周臨床試驗，兩組中161（83%）名隨機病人達到獲得改善，并且個體核心組異常值獲得改善。

結(jié)論:盡管兩組治療在主要終點和次要終點間無顯著差別，83%成人和青少年難治性肌炎患者獲得改善?？紤]不同的試驗設(shè)計，B細胞清除療法在治療肌炎的作用需要進一步研究。

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附原文：
Objective To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase trial in adult and pediatric myositis patients.
Methods Adults with refractory polymyositis (PM) and adults and children with refractory dermatomyositis (DM) were enrolled. Entry criteria included muscle weakness and ≥2 additional abnormal values on core set measures (CSMs) for adults. Juvenile DM patients required ≥3 abnormal CSMs, with or without muscle weakness. Patients were randomized to receive either rituximab early or rituximab late, and glucocorticoid or immunosuppressive therapy was allowed at study entry. The primary end point compared the time to achieve the International Myositis Assessment and Clinical Studies Group preliminary definition of improvement (DOI) between the 2 groups.The secondary end points were the time to achieve ≥20% improvement in muscle strength and the proportions of patients in the early and late rituximab groups achieving the DOI at week 8.
Results Among 200 randomized patients (76 with PM, 76 with DM, and 48 with juvenile DM), 195 showed no difference in the time to achieving the DOI between the rituximab late (n = 102) and rituximab early (n = 93) groups ( P = 0.74 by log rank test), with a median time to achieving a DOI of 20.2 weeks and 20.0 weeks, respectively. The secondary end points also did not significantly differ between the 2 treatment groups. However, 161 (83%) of the randomized patients met the DOI, and individual CSMs improved in both groups throughout the 44-week trial.
Conclusion Although there were no significant differences in the 2 treatment arms for the primary and secondary end points, 83% of adult and juvenile myositis patients with refractory disease met the DOI. The role of B cell–depleting therapies in myositis warrants further study, with consideration for a different trial design.

引自：Oddis C V, Reed A M, Aggarwal R, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial.[J]. Arthritis & Rheumatism, 2013, 65(2):314-24.