## **Supplemental Online Content**

Tedbirt B, Maho-Vaillant M, Houivet E, et al. Long-Term Sustained Complete Remission Without Corticosteroid Therapy in Patients with Pemphigus Who Received Rituximab as First-Line Therapy: Results From a Median 7-Year Follow-up Study of the Ritux 3 Trial. *JAMA Dermatol*. Published online January 24, 2024. doi:10.1001/jamadermatol.2023.5679

**eTable 1.** Baseline characteristics of patients who attended the end of follow-up visit, and those who were lost of follow-up before this end of follow-up visit

**eFigure 1.** Kaplan-Meier estimates of disease-free survival of patients who received rituximab as first-line treatment (blue curve) versus second-line treatment (red curve)

**eFigure 2,** Receiver operating characteristic (ROC) curves to predict long-term relapse on anti-desmoglein 1 and 3 antibody levels from month 36 to the extension study visit

This supplemental material has been provided by the authors to give readers additional information about their work.

**eTable 1: Baseline characteristics of patients who attended the end of follow-up visit, and those who were lost of follow-up before this end of follow-up visit.** 

| Characteristic | Patients who attended the lost of follow-up visit (n=83) | Patients lost to follow-up (n=7) | p-value |
|------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------|-------------------------------------------|---------|
| Age (years), mean (SD) | 53.6 (14.2) | 50.4 (23.8) | 0.74 |
| Sex, Male/Female | 34/49 | 6/1 | 0.04 |
| Duration between onset of disease and inclusion in protocol (months), mean (SD) | 6.7 (6.4) | 7.3 (10.6) | 0.60 |
| PDAI score, mean (SD) | 40.4 (27.4) | 28.4 (11.3) | 0.31 |
| Karnofsky score, mean (SD) | 91.9 (12.6) | 92.9 (9.5) | 0.92 |

**eFigure 1: Kaplan-Meier estimates of disease-free survival of patients who received rituximab as first-line treatment (blue curve) versus second-line treatment (red curve).** Time to relapse was calculated from the date of the first rituximab infusion to the end of the study.

![](https://assets.reachrx.ai/images/10.1001%E2%98%8Djamadermatol.2023.5679/_page_2_Figure_1.jpeg)

**eFigure 2: Receiver operating characteristic (ROC) curves to predict long-term relapse on anti-desmoglein 1 and 3 antibody levels from month 36 to the extension study visit.** (A) ROC curve for anti-desmoglein 1 antibody ELISA values ; (B) ROC curve for antidesmoglein 3 antibody ELISA values.

![](https://assets.reachrx.ai/images/10.1001%E2%98%8Djamadermatol.2023.5679/_page_3_Figure_1.jpeg)

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>

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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

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

Clinical Summary

What was studied

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