Department of Rheumatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris Sud, Université Paris Sud, INSERM U1012, Le Kremlin-Bicêtre, France.
Roche, Boulogne Billancourt, France.
Ann Rheum Dis. 2014 Aug;73(8):1508-14. doi: 10.1136/annrheumdis-2013-203480. Epub 2013 May 30.
The licensed dose of rituximab in rheumatoid arthritis (RA) is two doses of 1000 mg given 2 weeks apart. A lower dose has never been specifically studied in patients with an inadequate response to anti-tumour necrosis factor (TNF) agents.
To compare the efficacy and safety of rituximab repeat treatment with two doses (1000 mg×1 and 1000 mg×2) following initial treatment with 1000 mg×2.
We set up an open-label, prospective, multicentre, non-inferiority study comprising a non-controlled period (24 weeks) followed by a randomised controlled period (weeks 24-104) in patients with RA and an inadequate response to anti-TNF agents. All patients received one course of rituximab (1000 mg×2) with methotrexate. At week 24, patients achieving a EULAR response (moderate or good) were randomised to rituximab retreatment at 1000 mg×1 (Arm A) or 1000 mg×2 (Arm B). The primary objective measure was disease activity in 28 joints C-reactive protein (DAS28-CRP) area under the curve (AUC) over 104 weeks with a non-inferiority margin defined by 20% (444) of the mean DAS28-CRP AUC (mean±SD 2218±967) of the reference data.
The intent-to-treat and per-protocol (PP) populations comprised 143 (A/B: 70/73) and 100 (A/B: 51/49) patients, respectively. The adjusted mean difference in DAS28-CRP AUC (PP) was 51.4 (95% CI -131.2 to 234), demonstrating non-inferiority between arms A and B. The overall rituximab safety profile was similar with both retreatment regimens.
Following a clinical response to a first course of rituximab in RA at the licensed dose of 1000 mg×2, retreatment with rituximab at 1000 mg×1 results in efficacy outcomes that are non-inferior to those achieved with retreatment at 1000 mg×2.
NCT01126541.
类风湿关节炎（RA）中利妥昔单抗的许可剂量为每 2 周给予两次 1000mg，共两次。对于对抗肿瘤坏死因子（TNF）药物反应不足的患者，从未专门研究过较低剂量。
比较初始治疗给予 1000mg×2 后，重复使用两次剂量（1000mg×1 和 1000mg×2）与利妥昔单抗重复治疗的疗效和安全性。
我们建立了一项开放标签、前瞻性、多中心、非劣效性研究，包括初始治疗后 24 周的非对照期（24 周）和随后的随机对照期（24-104 周），纳入对 TNF 拮抗剂反应不足的 RA 患者。所有患者均接受甲氨蝶呤联合利妥昔单抗一个疗程（1000mg×2）。在第 24 周，达到 EULAR 反应（中度或良好）的患者被随机分配至利妥昔单抗重复治疗，剂量为 1000mg×1（A 组）或 1000mg×2（B 组）。主要疗效测量指标为 104 周时 28 个关节 C 反应蛋白（DAS28-CRP）曲线下面积（AUC）的疾病活动度，非劣效性边界定义为参考数据中 DAS28-CRP AUC 的平均值±标准差（2218±967）的 20%（444）。
意向治疗人群和符合方案人群分别包括 143 名（A/B：70/73）和 100 名（A/B：51/49）患者。DAS28-CRP AUC（PP）的调整平均差异为 51.4（95%CI-131.2 至 234），表明 A 组和 B 组之间无差异。两种治疗方案的利妥昔单抗总体安全性特征相似。
在 RA 患者接受利妥昔单抗 1000mg×2 的许可剂量治疗后出现临床应答后，用 1000mg×1 重复利妥昔单抗治疗可获得与用 1000mg×2 重复利妥昔单抗治疗相似的疗效。
NCT01126541。
