Department of Dermatology and Referral Center for Autoimmune Bullous Diseases (MALIBUL), Avicenne Hospital, Hôpitaux Universitaires de Paris Seine-Saint-Denis, AP-HP, Université Sorbonne Paris Nord, Bobigny, France.
Inserm UMR 1125 Li2P, UFR SMBH Léonard de Vinci, Université Sorbonne Paris Nord (USPN), Bobigny, France.
Front Immunol. 2022 Jun 30;13:915205. doi: 10.3389/fimmu.2022.915205. eCollection 2022.
Mucous membrane pemphigoid (MMP) is a heterogeneous group of rare, chronic, subepithelial autoimmune blistering diseases (AIBDs) with predominant involvement of mucous membranes that can be sight-threatening and life-threatening. Rituximab (RTX) has demonstrated its efficacy in severe MMP refractory to conventional immunosuppressants in small series that differed in RTX scheme, concomitant therapies, and outcome definitions. In a meta-analysis involving 112 patients with MMP treated with RTX, complete remission (CR) was reported in 70.5% of cases. Herein, we report the largest retrospective monocentric study on RTX efficacy in a series of 109 severe and/or refractory patients with MMP treated with RTX with a median follow-up period of 51.4 months. RTX was administered in association with immunomodulatory drugs (dapsone, salazopyrine) without any other systemic immunosuppressant in 104 patients. The RTX schedule comprised two injections (1 g, 2 weeks apart), repeated every 6 months until CR or failure, with a unique consolidation injection (1 g) after CR. The median survival times to disease control and to CR were 7.1 months and 12.2 months, respectively. The median number of RTX cycles required to achieve CR in 85.3% of patients was two. The larynx was the lesional site that took the longest time to achieve disease control. One year after RTX weaning, CR off RTX was obtained in 68.7% of cases. CR off RTX with only minimum doses of immunomodulatory drugs was achieved in 22.0% of patients. Further, 10.1% of patients were partial responders and 4.6% were non-responders to RTX. Relapse occurred in 38.7% of cases, of whom 91.7% had achieved CR again at the last follow-up. In MMP, CR was achieved in a longer time and after more rituximab cycles than in pemphigus, especially for patients with MMP with anti-type VII collagen reactivity. RTX with concomitant immunomodulatory drugs was not responsible for an unusual proportion of adverse events. This large study confirms that RTX is an effective therapy in patients with severe and/or refractory MMP, corroborating previous findings regarding the effects of RTX on AIBDs such as pemphigus.
黏膜性类天疱疮（Mucous membrane pemphigoid，MMP）是一组罕见的、慢性的、亚上皮自身免疫性疱病（Autoimmune blistering diseases，AIBDs），主要累及黏膜，可能导致视力丧失和生命危险。利妥昔单抗（Rituximab，RTX）在一系列针对常规免疫抑制剂难治性 MMP 的小系列研究中显示出疗效，这些研究在 RTX 方案、伴随治疗和结局定义方面存在差异。在一项涉及 112 例 MMP 患者接受 RTX 治疗的荟萃分析中，报告了 70.5%的完全缓解（Complete remission，CR）。在此，我们报告了一项最大的回顾性单中心研究，该研究涉及 109 例严重和/或难治性 MMP 患者，这些患者接受 RTX 治疗，中位随访时间为 51.4 个月。在 104 例患者中，RTX 与免疫调节剂（氨苯砜、柳氮磺胺吡啶）联合使用，未使用任何其他系统性免疫抑制剂。RTX 方案包括两次注射（1g，间隔 2 周），在 CR 或失败前每 6 个月重复一次，在 CR 后进行单次巩固注射（1g）。疾病控制和达到 CR 的中位生存时间分别为 7.1 个月和 12.2 个月。85.3%的患者需要进行两次 RTX 循环才能达到 CR。喉是达到疾病控制所需时间最长的病变部位。在 RTX 停药后 1 年，68.7%的患者达到了无 RTX 的 CR。22.0%的患者在仅使用最低剂量免疫调节剂的情况下达到了无 RTX 的 CR。此外，10.1%的患者对 RTX 有部分反应，4.6%的患者无反应。38.7%的患者出现复发，其中 91.7%在最后一次随访时再次达到 CR。在 MMP 中，达到 CR 的时间和需要的 RTX 循环次数都比天疱疮长，尤其是对于抗 VII 型胶原反应性 MMP 的患者。伴有免疫调节剂的 RTX 并不导致异常比例的不良事件。这项大型研究证实，RTX 是一种治疗严重和/或难治性 MMP 的有效方法，证实了之前关于 RTX 对天疱疮等 AIBD 影响的研究结果。
