JAMA Dermatology

<jats:sec id="ab-doi230070-1"><jats:title>Importance</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-doi230070-2"><jats:title>Objective</jats:title><jats:p>To assess the long-term efficacy and safety of the Ritux 3 treatment regimen.</jats:p></jats:sec><jats:sec id="ab-doi230070-3"><jats:title>Design, Setting, and Participants</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-doi230070-4"><jats:title>Exposure</jats:title><jats:p>Patients were initially randomized in the rituximab plus prednisone group or prednisone-alone group.</jats:p></jats:sec><jats:sec id="ab-doi230070-5"><jats:title>Main outcomes and measures</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec id="ab-doi230070-6"><jats:title>Results</jats:title><jats:p>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; <jats:italic>P</jats:italic> &amp;amp;lt; .001), and had about half the relapses (42.2% vs 83.7%; <jats:italic>P</jats:italic> &amp;amp;lt; .001). Patients who received rituximab as second-line treatment had shorter DFS than patients treated as first line (<jats:italic>P</jats:italic> = .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 (<jats:italic>P</jats:italic> = .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.</jats:p></jats:sec><jats:sec id="ab-doi230070-7"><jats:title>Conclusions and Relevance</jats:title><jats:p>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.</jats:p></jats:sec>

First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial.

Lancet

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

Br J Dermatol

Rituximab versus mycophenolate mofetil in patients with pemphigus vulgaris.

N Engl J Med

Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response.

Sci Transl Med

Rituximab and corticosteroid effect on desmoglein-specific B cells and desmoglein-specific T follicular helper cells in pemphigus.

J Invest Dermatol

Modifications of the transcriptomic profile of autoreactive B cells from pemphigus patients after treatment with rituximab or a standard corticosteroid regimen.

Front Immunol

Factors associated with short-term relapse in patients with pemphigus who receive rituximab as first-line therapy: a post hoc analysis of a randomized clinical trial.

JAMA Dermatol

Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus.

J Am Acad Dermatol

Long-term outcomes of rituximab therapy in pemphigus.

J Eur Acad Dermatol Venereol

Rituximab treatment of severe pemphigus: long-term results including immunologic follow-up.

Rituximab therapy in pemphigus: a long-term follow-up.

Dermatol Ther

Temporal outcomes after rituximab therapy for pemphigus vulgaris.

Increase of interleukin-10-producing B cells associated with long-term remission after i.v. immunoglobulin treatment for pemphigus.

J Dermatol

Identification of autoreactive B cell subpopulations in peripheral blood of autoimmune patients with pemphigus vulgaris.

Impaired function of CD19(+) CD24(hi) CD38(hi) regulatory B cells in patients with pemphigus.

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.
To assess the long-term efficacy and safety of the Ritux 3 treatment regimen.
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.
Patients were initially randomized in the rituximab plus prednisone group or prednisone-alone group.
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.
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.
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.

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

Sustained Remission Without Corticosteroids Among Patients With Pemphigus Who Had Rituximab as First-Line Therapy

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