Long-Term, Sustained Remission of Pemphigus Observed in Patients Treated with Rituximab

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These data were the results of the secondary analysis of the Ritux 3 study, as the treatment’s short-term efficacy and safety had been confirmed previously.

There is an association between long-term complete pemphigus remission and first-line treatment using rituximab and without use of corticosteroid therapy or further maintenance infusion of rituximab, according to new findings.1

These findings resulted from a long term evaluation of the results among participants in the Ritux 3 study. The research was led by Billal Tedbirt, MD, from the department of dermatology at CHU Rouen and INSERM U1234 of Normandie University in Rouen, France.

Tedbirt and colleagues noted that there had been a limited amount of relapses observed between the second and third years immediately after initiation of treatment in the Ritux 3 trial, hypothesizing that first-line treatment would be linked to a diminished risk of long-term relapses compared to other options.2

“The primary objective of this study was to assess the 5- and 7-year disease-free survival (DFS) off corticosteroids therapy from the date of achievement of CR without corticosteroids therapy to the end of the follow-up visit,” Tedbirt and colleagues wrote.


The Ritux 3 trial had been carried out within 25 dermatology departments found across France, with research taking place from January 2010 - December 2015. Overall, the team’s analysis had constituted a 24-month randomized, open-label trial that was designed to compare the safety and efficacy of rituximab combined with short-term corticosteroids therapy (rituximab plus prednisone group) against a standard high-dose regimen of oral corticosteroids (prednisone-alone group) as initial treatment for the 90 participants with new diagnoses of pemphigus.

Those in the rituximab plus prednisone arm were given 1 g of the drug on day 0 and then later on day 14, followed by 500 mg at the 12 and 18-month marks. Those who were able to finish the Ritux 3 trial successfully were considered by the team as eligible for inclusion in their extended follow-up assessment.

The investigators scheduled an end-of-follow-up meeting between March 2017 - November 2020 to look into 7-year data of the participants, depending upon their date of enrollment in Ritux 3.

As the end-of-follow-up visit took place, the research team gathered various clinical data, some of which included participants’ clinical status (i.e., complete remission without corticosteroids therapy or minimal therapy, occurrence of partial remission, or reported relapse). This would be based on consensus definitions previously established, and the team would assess from the 36-month visit to the end of the follow-up visit.

Furthermore, the investigators looked into the number and doses of rituximab infusions which had been administered and assessed the occurrence of severe adverse events (SAEs). Subjects’ serum samples were gathered at the month 36 assessment and during the end-of-follow-up meeting, with the team measuring anti-Dsg1 and anti-Dsg3 IgG Abs implementing a positivity threshold of 20 IU/mL.

There had been 90 participants enrolled in Ritux 3, and 83 were given an evaluation at the conclusion of the investigators’ follow-up study meeting. There were 44 placed in the rituximab plus prednisone cohort and 39 placed in the prednisone-alone cohort, with a median (IQR) follow-up duration of 87.3 (79.1-97.5) months.


93% of patients from the rituximab plus prednisone group and 39% from the prednisone-alone group were shown to have achieved total remission without corticosteroids at any point at the point of follow-up. Overall, the investigators reported that the rituximab cohort had much longer 5- and 7-year disease-free survival (DFS) without corticosteroids as opposed to those in the prednisone-alone cohort (76.7% and 72.1% compared to 35.3% and 35.3%, respectively; P<.001).

The rituximab cohort also experienced around half the relapse rate (42.2% vs. 83.7%; P<.001). Those given rituximab as a second-line intervention were shown by the research team to have had a shorter DFS compared to participants treated in the first-line (P=.007). The team noted that the rituximab plus prednisone arm of the study showed fewer serious adverse events (SAEs) versus those in the prednisone-alone arm, with 31 and 58 SAEs, respectively (P=.003).

The use of anti-Dsg1 values of 20 or more IU/mL and/or anti-Dsg3 values of 48 or more IU/mL was shown by the investigators to have a positive predictive value of 0.83 and to have a negative predictive value of 0.94 as far as predicting participants’ long-term relapse.

“Overall, this study showed that the first-line treatment of patients with pemphigus with rituximab was associated with sustained CR without corticosteroids therapy up to 7 years after the start of treatment, without any additional maintenance infusions of rituximab,” they wrote. “It also suggests the possibility of identifying patients with a high risk of relapse based on ELISA values of anti-Dsg Abs to re-treat only these latter patients to prevent the occurrence of relapse.”


  1. Tedbirt B, Maho-Vaillant M, Houivet E, et al. Sustained Remission Without Corticosteroids Among Patients With Pemphigus Who Had Rituximab as First-Line Therapy: Follow-Up of the Ritux 3 Trial. JAMA Dermatol. Published online January 24, 2024. doi:10.1001/jamadermatol.2023.5679.
  2. Colliou N, Picard D, Caillot F, et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci Transl Med. 2013;5(175):175ra30. doi:10.1126/scitranslmed.3005166.