Hébert Vivien, Hamwi Sami, Tancrède-Bohin Emmanuelle, Quéreux Gaelle, Pham-Ledard Anne, Caux Frédéric, Tedbirt Billal, Lefebvre Alexis, Cordel Nadège, Alexandre Marina, Viguier Manuelle, Jeudy Géraldine, D'Incan Michel, Debarbieux Sébastien, Brue Alexis, Duvert-Lehembre Sophie, Fenot Marion, Seta Vannina, Ingen-Housz-Oro Saskia, Lepelletier Clémence, Joly Pascal
Department of Dermatology, Centre Hospitalier Universitaire de Rouen and Institut National de la Santé et de la Recherche Médicale (INSERM) U1234, Normandie University, Rouen, France.
Dermatology Department, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.
JAMA Dermatol. 2025 Apr 1;161(4):399-405. doi: 10.1001/jamadermatol.2024.6130.
Rituximab is approved for the treatment of moderate to severe pemphigus. However, 20% of patients in the RITUX 3 trial relapsed within the first year of treatment.
To assess the outcome of an additional rituximab infusion at month 6 in patients with pemphigus who were in complete remission (CR) after rituximab regimen but had 1 or more predictors of relapse at month 3.
DESIGN, SETTINGS, AND PARTICIPANTS: This multicenter cohort study was conducted in France from September 2018 to June 2023 to assess patients with newly diagnosed pemphigus who were in CR after treatment with the RITUX 3 regimen but had predictors of relapse at month 3. Relapse factors were a Pemphigus Disease Area Index (PDAI) score of 45 or higher, desmoglein 1 (DSG1) antibodies greater than 20 IU/mL, and/or DSG3 antibodies greater than 130 IU/mL.
Patients in CR at month 6 with at least 1 predictor of relapse were treated with an additional rituximab infusion at month 6.
Primary end point was the rate of CR without corticosteroid therapy for 2 months at month 12. Secondary end points were the rate of relapse, number of patients needing to be re-treated (NNT) with rituximab to avoid a relapse, and safety.
The study population comprised 87 patients (44 females [50.6%] and 43 [49.4%] males), with a mean (SD [range]) age of 55.3 (15.2 [24-92]) years at pemphigus diagnosis. Of these, 64 patients (73.6%) had pemphigus vulgaris and 23 (26.4%) had pemphigus foliaceus. At month 6, CR had been achieved by 77 patients (88.5%), and 10 (11.5%) had persistent disease activity. Of the 77 patients in CR, 30 (39.0%) had at least 1 predictor of relapse and received an additional infusion of rituximab; 47 patients (61.0%) without a predictor did not. Two patients without a predictor and no patients with a predictor experienced relapse-an overall relapse rate of 2.6% and an NNT of 3.6 (95% CI, 1.6-46.5). The 10 patients (11.5%) with persistent disease activity at month 6 were re-treated with rituximab, 2000 mg. At month 12, the rate of CR without corticosteroid therapy for a minimum of 2 months was 72 of 77 (93.5%) among patients who had achieved CR at month 6, and 72 of 87 (82.7%) for the whole study population. Eight serious adverse effects were reported among 5 patients; there were no deaths.
This multicenter cohort study indicates that using predictors such as baseline PDAI score, anti-DSG1 antibodies, and/or anti-DSG3 antibodies to initiate preemptive treatment with additional rituximab may reduce the rate of short-term relapse.
利妥昔单抗已被批准用于治疗中度至重度天疱疮。然而，在RITUX 3试验中，20%的患者在治疗的第一年内复发。
评估在接受利妥昔单抗治疗方案后达到完全缓解（CR）但在第3个月有1个或更多复发预测因素的天疱疮患者中，在第6个月额外输注利妥昔单抗的效果。
设计、地点和参与者：这项多中心队列研究于2018年9月至2023年6月在法国进行，以评估新诊断的天疱疮患者，这些患者在接受RITUX 3方案治疗后达到CR，但在第3个月有复发预测因素。复发因素为天疱疮疾病面积指数（PDAI）评分45或更高、桥粒芯糖蛋白1（DSG1）抗体大于20 IU/mL和/或DSG3抗体大于130 IU/mL。
在第6个月达到CR且至少有1个复发预测因素的患者在第6个月接受额外的利妥昔单抗输注。
主要终点是在第12个月无需皮质类固醇治疗2个月的CR率。次要终点是复发率、需要用利妥昔单抗重新治疗以避免复发的患者数量（NNT）和安全性。
研究人群包括87例患者（44例女性[50.6%]和43例男性[49.4%]），天疱疮诊断时的平均（标准差[范围]）年龄为55.3（15.2[24 - 92]）岁。其中，64例患者（73.6%）患有寻常型天疱疮，23例（26.4%）患有落叶型天疱疮。在第6个月，77例患者（88.5%）达到CR，10例（11.5%）有持续的疾病活动。在77例达到CR的患者中，30例（39.0%）至少有1个复发预测因素并接受了额外的利妥昔单抗输注；47例（61.0%）没有预测因素的患者未接受。没有预测因素的2例患者和有预测因素的患者均未复发——总体复发率为2.6%，NNT为3.6（95%CI，1.6 - 46.5）。在第6个月有持续疾病活动的10例患者（11.5%）用2000 mg利妥昔单抗重新治疗。在第12个月，在第6个月达到CR的患者中，77例中有72例（93.5%）无需皮质类固醇治疗至少2个月达到CR，整个研究人群中87例中有72例（82.7%）。5例患者报告了8例严重不良反应；无死亡病例。
这项多中心队列研究表明，使用基线PDAI评分、抗DSG1抗体和/或抗DSG3抗体等预测因素启动额外利妥昔单抗的抢先治疗可能会降低短期复发率。
