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Randomized Controlled Trial
. 2024 Mar 1;160(3):290-296.
doi: 10.1001/jamadermatol.2023.5679.

Sustained Remission Without Corticosteroids Among Patients With Pemphigus Who Had Rituximab as First-Line Therapy: Follow-Up of the Ritux 3 Trial

Billal Tedbirt  1 , Maud Maho-Vaillant  1 , Estelle Houivet  2 , Claire Mignard  1 , Marie-Laure Golinski  1 , Sébastien Calbo  1 , Catherine Prost-Squarcioni  3 , Bruno Labeille  4 , Catherine Picard-Dahan  5 , Guillaume Chaby  6 , Marie-Aleth Richard  7 , Emmanuelle Tancrede-Bohin  8 , Sophie Duvert-Lehembre  9 , Emmanuel Delaporte  9 , Philippe Bernard  10 , Frédéric Caux  3 , Marina Alexandre  3 , Philippe Musette  3 , Saskia Ingen-Housz-Oro  11 , Pierre Vabres  12 , Gaëlle Quereux  13 , Alain Dupuy  14 , Sébastien Debarbieux  15 , Martine Avenel-Audran  16 , Michel D'Incan  17 , Christophe Bédane  18 , Nathalie Bénéton  19 , Denis Jullien  20 , Nicolas Dupin  21 , Laurent Misery  22 , Laurent Machet  23 , Marie Beylot-Barry  24 , Olivier Dereure  25 , Bruno Sassolas  26 , Jacques Benichou  27 , Pascal Joly  1 , Vivien Hébert  1 ; French Reference Center for Autoimmune Blistering Diseases MALIBUL
Affiliations
Randomized Controlled Trial

Sustained Remission Without Corticosteroids Among Patients With Pemphigus Who Had Rituximab as First-Line Therapy: Follow-Up of the Ritux 3 Trial

Billal Tedbirt et al. JAMA Dermatol. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Caux reported being an investigator from Argenx, Principia Biopharma, and Regeneron, and personal fees from Sanofi outside the submitted work. Dr Jullien reported personal fees from AbbVie, from Almirall, Amgen, BMS, Boehringer Ingelheim, Celgene, Janssen-Cilag, LEO, Lilly, MSD, MEDAC, Novartis, Pfizer, Sanofi, and UCB outside the submitted work. Dr Joly reported personal fees from Argenx and Janssen outside the submitted work. Dr Hébert reported personal fees from Lilly, AbbVie, Pfizer, and UCB outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Chart of Patients Included in the Ritux 3 Trial
CR indicates complete remission. aAt the last evaluation, these patients were in CR without corticosteroid therapy. bAt the last evaluation, these 3 patients had relapsed and had active disease.
Figure 2.
Figure 2.. Kaplan-Meier Estimates of Disease-Free Survival (DFS) of Patients Both Still Receiving Corticosteroids and Without Corticosteroids
The DFS survival curves were calculated by taking into account the 44 patients (97.8%) from the rituximab plus prednisone group and the 43 patients (97.7%) from the prednisone-alone group who achieved disease control during the Ritux 3 trial. The orange curve indicates those who were initially randomized in the rituximab plus prednisone group and the blue curve the prednisone-alone group.
Figure 3.
Figure 3.. Kaplan-Meier Estimates of Disease-Free Survival (DFS) Without Corticosteroid Therapy
The DFS estimates without corticosteroid survival curves were calculated by taking into account the 43 patients (93.5%) from the rituximab plus prednisone and the 17 patients (38.6%) from the prednisone-alone group who achieved complete remission off corticosteroid therapy. The orange curve indicates patients initially randomized to the rituximab plus prednisone group and the blue curve the prednisone-alone group.
See this image and copyright information in PMC

References

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