학술논문
Sustained Remission Without Corticosteroids Among Patients With Pemphigus Who Had Rituximab as First-Line Therapy: Follow-Up of the Ritux 3 Trial.
Document Type
Academic Journal
Author
Tedbirt B; Department of Dermatology, CHU Rouen and INSERM U1234, Normandie University, Rouen, France.; Maho-Vaillant M; Department of Dermatology, CHU Rouen and INSERM U1234, Normandie University, Rouen, France.; Houivet E; Department of Biostatistics and Clinical Research, CHU Rouen, Rouen, France.; Mignard C; Department of Dermatology, CHU Rouen and INSERM U1234, Normandie University, Rouen, France.; Golinski ML; Department of Dermatology, CHU Rouen and INSERM U1234, Normandie University, Rouen, France.; Calbo S; Department of Dermatology, CHU Rouen and INSERM U1234, Normandie University, Rouen, France.; Prost-Squarcioni C; Department of Dermatology, Centre de référence des maladies bulleuses auto-immunes, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris 13, Bobigny, France.; Labeille B; Department of Dermatology, University of Saint-Étienne, Saint-Étienne, France.; Picard-Dahan C; Department of Dermatology, Bichat Hospital, University of Paris 10, Paris, France.; Chaby G; Department of Dermatology, University of Amiens, Amiens, France.; Richard MA; CEReSS-EA 3279, Research Centre in Health Services and Quality of Life Aix Marseille University, Dermatology Department, Universitaire Hospital Timone, Assistance Publique Hôpitaux de Marseille, APHM, 13385, Marseille, France.; Tancrede-Bohin E; Department of Dermatology, St Louis Hospital, Paris 7 Sorbonne Paris Cité University, Paris, France.; Duvert-Lehembre S; Department of Dermatology, University of Lille, Lille, France.; Delaporte E; Department of Dermatology, University of Lille, Lille, France.; Bernard P; Department of Dermatology, University of Reims, Reims, France.; Caux F; Department of Dermatology, Centre de référence des maladies bulleuses auto-immunes, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris 13, Bobigny, France.; Alexandre M; Department of Dermatology, Centre de référence des maladies bulleuses auto-immunes, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris 13, Bobigny, France.; Musette P; Department of Dermatology, Centre de référence des maladies bulleuses auto-immunes, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris 13, Bobigny, France.; Ingen-Housz-Oro S; Department of Dermatology, Assistance Publique-Hôpitaux de Paris, Henri Mondor Hospital, Univ Paris Est Créteil EpiDermE, Créteil, France.; Vabres P; Department of Dermatology, Dijon University Hospital, Dijon, France.; Quereux G; Department of Dermatology, University of Nantes, Nantes, France.; Dupuy A; Department of Dermatology, University of Rennes, Rennes, France.; Debarbieux S; Department of Dermatology, Centre Hospitalier Lyon Sud, Pierre Bénite, Lyon, France.; Avenel-Audran M; Department of Dermatology, University of Angers, Angers, France.; D'Incan M; Department of Dermatology, University of Clermont-Ferrand, Clermont-Ferrand, France.; Bédane C; Department of Dermatology, University of Limoges, Limoges, France.; Bénéton N; Department of Dermatology, Le Mans General Hospital, Le Mans, France.; Jullien D; Department of Dermatology, Edouard Herriot Hospital, Lyon Claude Bernard University, Lyon, France.; Dupin N; Department of Dermatology, APHP and University of Paris cité, Paris, France.; Misery L; Department of Dermatology, Brest University Hospital, Brest, France.; Machet L; Department of Dermatology, Tours University Hospital, Tours, France.; Beylot-Barry M; Department of Dermatology, University of Bordeaux, Bordeaux, France.; Dereure O; Department of Dermatology, University of Montpellier, Montpellier, France.; Sassolas B; Department of Internal Medicine, Brest University Hospital, Brest, France.; Benichou J; Department of Biostatistics and Clinical Research, CHU Rouen and Inserm U1018, Université Paris-Saclay and Université de Rouen, Rouen, France.; Joly P; Department of Dermatology, CHU Rouen and INSERM U1234, Normandie University, Rouen, France.; Hébert V; Department of Dermatology, CHU Rouen and INSERM U1234, Normandie University, Rouen, France.
Source
Publisher: American Medical Association Country of Publication: United States NLM ID: 101589530 Publication Model: Print Cited Medium: Internet ISSN: 2168-6084 (Electronic) Linking ISSN: 21686068 NLM ISO Abbreviation: JAMA Dermatol Subsets: MEDLINE
Subject
Language
English
Abstract
Importance: The Ritux 3 trial demonstrated the short-term efficacy and safety of first-line treatment with rituximab compared with a standard corticosteroid regimen in pemphigus. No data on the long-term follow-up of patients who received rituximab as first line are available.
Objective: To assess the long-term efficacy and safety of the Ritux 3 treatment regimen.
Design, Setting, and Participants: This 7-year follow-up study of the Ritux 3 trial included patients with pemphigus from 25 dermatology departments in France from January 1, 2010, to December 31, 2015.
Exposure: Patients were initially randomized in the rituximab plus prednisone group or prednisone-alone group.
Main Outcomes and Measures: The primary outcome was the 5- and 7-year disease-free survival (DFS) without corticosteroids, assessed by Kaplan-Meier curves. Secondary outcomes were occurrence of relapse, occurrence of severe adverse events (SAEs), and evolution of antidesmoglein (Dsg) antibody enzyme-linked immunosorbent assay values to predict long-term relapse.
Results: Of the 90 patients in the Ritux 3 trial, 83 were evaluated at the end of follow-up study visit (44 in the rituximab plus prednisone group; 39 in the prednisone-alone group) with a median (IQR) follow-up of 87.3 (79.1-97.5) months. Forty-three patients (93%) from the rituximab plus prednisone and 17 patients (39%) from the prednisone-alone group had achieved complete remission without corticosteroids at any time during the follow-up. Patients from the rituximab group had much longer 5- and 7-year DFS without corticosteroids than patients from the prednisone-alone group (76.7% and 72.1% vs 35.3% and 35.3%, respectively; P < .001), and had about half the relapses (42.2% vs 83.7%; P < .001). Patients who received rituximab as second-line treatment had shorter DFS than patients treated as first line (P = .007). Fewer SAEs were reported in the rituximab plus prednisone group compared with the prednisone-alone group, 31 vs 58 respectively, corresponding to 0.67 and 1.32 SAEs per patient, respectively (P = .003). The combination of anti-Dsg1 values of 20 or more IU/mL and/or anti-Dsg3 values of 48 or more IU/mL yielded 0.83 positive predictive value and 0.94 negative predictive value to predict long-term relapse.
Conclusions and Relevance: In this secondary analysis of the Ritux 3 trail, first-line treatment of patients with pemphigus with the Ritux 3 regimen was associated with long-term sustained complete remission without corticosteroid therapy without any additional maintenance infusion of rituximab.
Objective: To assess the long-term efficacy and safety of the Ritux 3 treatment regimen.
Design, Setting, and Participants: This 7-year follow-up study of the Ritux 3 trial included patients with pemphigus from 25 dermatology departments in France from January 1, 2010, to December 31, 2015.
Exposure: Patients were initially randomized in the rituximab plus prednisone group or prednisone-alone group.
Main Outcomes and Measures: The primary outcome was the 5- and 7-year disease-free survival (DFS) without corticosteroids, assessed by Kaplan-Meier curves. Secondary outcomes were occurrence of relapse, occurrence of severe adverse events (SAEs), and evolution of antidesmoglein (Dsg) antibody enzyme-linked immunosorbent assay values to predict long-term relapse.
Results: Of the 90 patients in the Ritux 3 trial, 83 were evaluated at the end of follow-up study visit (44 in the rituximab plus prednisone group; 39 in the prednisone-alone group) with a median (IQR) follow-up of 87.3 (79.1-97.5) months. Forty-three patients (93%) from the rituximab plus prednisone and 17 patients (39%) from the prednisone-alone group had achieved complete remission without corticosteroids at any time during the follow-up. Patients from the rituximab group had much longer 5- and 7-year DFS without corticosteroids than patients from the prednisone-alone group (76.7% and 72.1% vs 35.3% and 35.3%, respectively; P < .001), and had about half the relapses (42.2% vs 83.7%; P < .001). Patients who received rituximab as second-line treatment had shorter DFS than patients treated as first line (P = .007). Fewer SAEs were reported in the rituximab plus prednisone group compared with the prednisone-alone group, 31 vs 58 respectively, corresponding to 0.67 and 1.32 SAEs per patient, respectively (P = .003). The combination of anti-Dsg1 values of 20 or more IU/mL and/or anti-Dsg3 values of 48 or more IU/mL yielded 0.83 positive predictive value and 0.94 negative predictive value to predict long-term relapse.
Conclusions and Relevance: In this secondary analysis of the Ritux 3 trail, first-line treatment of patients with pemphigus with the Ritux 3 regimen was associated with long-term sustained complete remission without corticosteroid therapy without any additional maintenance infusion of rituximab.