Internal Medicine, Referral Center for Rare Systemic and Autoimmune Diseases: Vasculitis and Scleroderma, Cochin Hospital, Paris Descartes University, Paris, France.
Department of Internal Medicine, Institut Mutualiste Montsouris, Paris, France.
Ann Rheum Dis. 2018 Aug;77(8):1143-1149. doi: 10.1136/annrheumdis-2017-212878. Epub 2018 Apr 25.
To compare individually tailored, based on trimestrial biological parameter monitoring, to fixed-schedule rituximab reinfusion for remission maintenance of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs).
Patients with newly diagnosed or relapsing granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in complete remission after induction therapy were included in an open-label, multicentre, randomised controlled trial. All tailored-arm patients received a 500 mg rituximab infusion at randomisation, with rituximab reinfusion only when CD19+B lymphocytes or ANCA had reappeared or ANCA titre rose markedly based on trimestrial testing until month 18. Controls received a fixed 500 mg rituximab infusion on days 0 and 14 postrandomisation, then 6, 12 and 18 months after the first infusion. The primary endpoint was the number of relapses (new or reappearing symptom(s) or worsening disease with Birmingham Vasculitis Activity Score (BVAS)>0) at month 28 evaluated by an independent Adjudication Committee blinded to treatment group.
Among the 162 patients (mean age: 60 years; 42% women) included, 117 (72.2%) had GPA and 45 (27.8%) had MPA. Preinclusion induction therapy included cyclophosphamide for 100 (61.7%), rituximab for 61 (37.6%) and methotrexate for 1 (0.6%). At month 28, 21 patients had suffered 22 relapses: 14/81 (17.3%) in 13 tailored-infusion recipients and 8/81 (9.9%) in 8 fixed-schedule patients (p=0.22). The tailored-infusion versus fixed-schedule group, respectively, received 248 vs 381 infusions, with medians (IQR) of 3 (2-4) vs 5 (5-5) administrations.
AAV relapse rates did not differ significantly between individually tailored and fixed-schedule rituximab regimens. Individually tailored-arm patients received fewer rituximab infusions.
NCT01731561; Results.
比较基于季度生物学参数监测的个体化定制方案与固定方案利妥昔单抗输注在抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）缓解期维持治疗中的效果。
本开放标签、多中心、随机对照试验纳入了诱导治疗后完全缓解的新诊断或复发的肉芽肿性多血管炎（GPA）或显微镜下多血管炎（MPA）患者。所有个体化定制组患者在随机分组时接受一次 500mg 利妥昔单抗输注，仅当基于季度检测出现 CD19+B 淋巴细胞或 ANCA 复现或 ANCA 滴度显著升高时，才输注利妥昔单抗，直至第 18 个月。对照组在随机分组后第 0 天和第 14 天接受一次固定剂量的 500mg 利妥昔单抗输注，然后在第一次输注后第 6、12 和 18 个月时再输注。主要终点是由独立的盲法评估委员会评估的第 28 个月时的复发（新出现或再现的症状或疾病恶化，Birmingham Vasculitis Activity Score（BVAS）>0）例数。
在纳入的 162 例患者（平均年龄 60 岁，42%为女性）中，117 例（72.2%）为 GPA，45 例（27.8%）为 MPA。入组前诱导治疗包括环磷酰胺 100 例（61.7%）、利妥昔单抗 61 例（37.6%）和甲氨蝶呤 1 例（0.6%）。在第 28 个月时，21 例患者发生了 22 次复发：13 例个体化定制输注组中有 14 例（17.3%）复发，8 例固定方案组中有 8 例（9.9%）复发（p=0.22）。个体化定制输注组和固定方案组分别接受了 248 次和 381 次输注，中位数（IQR）分别为 3（2-4）次和 5（5-5）次。
AAV 复发率在个体化定制和固定方案利妥昔单抗方案之间无显著差异。个体化定制组患者接受的利妥昔单抗输注次数更少。
NCT01731561；研究结果。
