Sustained Remission Without Corticosteroids Among Patients With Pemphigus Who Had Rituximab as First-Line Therapy
Authors: Tedbirt Billal , Maho-Vaillant Maud , Houivet Estelle , Mignard Claire , Golinski Marie-Laure , Calbo Sébastien , Prost-Squarcioni Catherine , Labeille Bruno , Picard-Dahan Catherine , Chaby Guillaume , Richard Marie-Aleth , Tancrede-Bohin Emmanuelle , Duvert-Lehembre Sophie , Delaporte Emmanuel , Bernard Philippe , Caux Frédéric , Alexandre Marina , Musette Philippe , Ingen-Housz-Oro Saskia , Vabres Pierre , Quereux Gaëlle , Dupuy Alain , Debarbieux Sébastien , Avenel-Audran Martine , D’Incan Michel , Bédane Christophe , Bénéton Nathalie , Jullien Denis , Dupin Nicolas , Misery Laurent , Machet Laurent , Beylot-Barry Marie , Dereure Olivier , Sassolas Bruno , Benichou Jacques , Joly Pascal , Hébert Vivien ,   French Reference Center for Autoimmune Blistering Diseases MALIBUL
Published: January 2024

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 &amp;lt; .001), and had about half the relapses (42.2% vs 83.7%; P &amp;lt; .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.