Cargando…

Rituximab Therapy for Mucous Membrane Pemphigoid: A Retrospective Monocentric Study With Long-Term Follow-Up in 109 Patients

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Bohelay, Gérôme, Alexandre, Marina, Le Roux-Villet, Christelle, Sitbon, Ishaï, Doan, Serge, Soued, Isaac, Shourick, Jason, Rousset, Laurie, Mellottee, Benoît, Heller, Michel, Lièvre, Nicole, Zumelzu, Coralie, Morin, Florence, Grootenboer-Mignot, Sabine, Gabison, Eric, Caux, Frédéric, Prost-Squarcioni, Catherine, Musette, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281543/
https://www.ncbi.nlm.nih.gov/pubmed/35844526
http://dx.doi.org/10.3389/fimmu.2022.915205
_version_ 1784746903466934272
author Bohelay, Gérôme
Alexandre, Marina
Le Roux-Villet, Christelle
Sitbon, Ishaï
Doan, Serge
Soued, Isaac
Shourick, Jason
Rousset, Laurie
Mellottee, Benoît
Heller, Michel
Lièvre, Nicole
Zumelzu, Coralie
Morin, Florence
Grootenboer-Mignot, Sabine
Gabison, Eric
Caux, Frédéric
Prost-Squarcioni, Catherine
Musette, Philippe
author_facet Bohelay, Gérôme
Alexandre, Marina
Le Roux-Villet, Christelle
Sitbon, Ishaï
Doan, Serge
Soued, Isaac
Shourick, Jason
Rousset, Laurie
Mellottee, Benoît
Heller, Michel
Lièvre, Nicole
Zumelzu, Coralie
Morin, Florence
Grootenboer-Mignot, Sabine
Gabison, Eric
Caux, Frédéric
Prost-Squarcioni, Catherine
Musette, Philippe
author_sort Bohelay, Gérôme
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9281543
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92815432022-07-15 Rituximab Therapy for Mucous Membrane Pemphigoid: A Retrospective Monocentric Study With Long-Term Follow-Up in 109 Patients Bohelay, Gérôme Alexandre, Marina Le Roux-Villet, Christelle Sitbon, Ishaï Doan, Serge Soued, Isaac Shourick, Jason Rousset, Laurie Mellottee, Benoît Heller, Michel Lièvre, Nicole Zumelzu, Coralie Morin, Florence Grootenboer-Mignot, Sabine Gabison, Eric Caux, Frédéric Prost-Squarcioni, Catherine Musette, Philippe Front Immunol Immunology 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. Frontiers Media S.A. 2022-06-30 /pmc/articles/PMC9281543/ /pubmed/35844526 http://dx.doi.org/10.3389/fimmu.2022.915205 Text en Copyright © 2022 Bohelay, Alexandre, Le Roux-Villet, Sitbon, Doan, Soued, Shourick, Rousset, Mellottee, Heller, Lièvre, Zumelzu, Morin, Grootenboer-Mignot, Gabison, Caux, Prost-Squarcioni and Musette https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Bohelay, Gérôme
Alexandre, Marina
Le Roux-Villet, Christelle
Sitbon, Ishaï
Doan, Serge
Soued, Isaac
Shourick, Jason
Rousset, Laurie
Mellottee, Benoît
Heller, Michel
Lièvre, Nicole
Zumelzu, Coralie
Morin, Florence
Grootenboer-Mignot, Sabine
Gabison, Eric
Caux, Frédéric
Prost-Squarcioni, Catherine
Musette, Philippe
Rituximab Therapy for Mucous Membrane Pemphigoid: A Retrospective Monocentric Study With Long-Term Follow-Up in 109 Patients
title Rituximab Therapy for Mucous Membrane Pemphigoid: A Retrospective Monocentric Study With Long-Term Follow-Up in 109 Patients
title_full Rituximab Therapy for Mucous Membrane Pemphigoid: A Retrospective Monocentric Study With Long-Term Follow-Up in 109 Patients
title_fullStr Rituximab Therapy for Mucous Membrane Pemphigoid: A Retrospective Monocentric Study With Long-Term Follow-Up in 109 Patients
title_full_unstemmed Rituximab Therapy for Mucous Membrane Pemphigoid: A Retrospective Monocentric Study With Long-Term Follow-Up in 109 Patients
title_short Rituximab Therapy for Mucous Membrane Pemphigoid: A Retrospective Monocentric Study With Long-Term Follow-Up in 109 Patients
title_sort rituximab therapy for mucous membrane pemphigoid: a retrospective monocentric study with long-term follow-up in 109 patients
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281543/
https://www.ncbi.nlm.nih.gov/pubmed/35844526
http://dx.doi.org/10.3389/fimmu.2022.915205
work_keys_str_mv AT bohelaygerome rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT alexandremarina rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT lerouxvilletchristelle rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT sitbonishai rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT doanserge rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT souedisaac rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT shourickjason rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT roussetlaurie rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT mellotteebenoit rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT hellermichel rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT lievrenicole rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT zumelzucoralie rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT morinflorence rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT grootenboermignotsabine rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT gabisoneric rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT cauxfrederic rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT prostsquarcionicatherine rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients
AT musettephilippe rituximabtherapyformucousmembranepemphigoidaretrospectivemonocentricstudywithlongtermfollowupin109patients