System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Multicenter Study Ppublish 5 citations

PubMed: 39908046 DOI: 10.1001/jamadermatol.2024.6130

Optimizing Pemphigus Management With Rituximab and Short-Term Relapse Predictors.

JAMA Dermatol 161(4):399-405

Authors: Vivien Hébert, Sami Hamwi, Emmanuelle Tancrède-Bohin, Gaelle Quéreux, Anne Pham-Ledard, Frédéric Caux, Billal Tedbirt, Alexis Lefebvre, Nadège Cordel, Marina Alexandre, Manuelle Viguier, Géraldine Jeudy, Michel D'Incan, Sébastien Debarbieux, Alexis Brue, Sophie Duvert-Lehembre, Marion Fenot, Vannina Seta, Saskia Ingen-Housz-Oro, Clémence Lepelletier, Pascal Joly

Affiliations

  • Department of Dermatology, Centre Hospitalier Universitaire de Rouen and Institut National de la Santé et de la Recherche Médicale (INSERM) U1234, Normandie University, Rouen, France.
  • Dermatology Department, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.
  • Department of Dermatology, University of Nantes, Nantes, France.
  • Dermatology Department, Centre Hospitalier Universitaire Bordeaux and INSERM U1312, Bordeaux Institute of Oncology, Translational Research on Oncodermatology and Rare Skin Diseases, Bordeaux University, Bordeaux, France.
  • Department of Dermatology, Centre de Référence des Maladies Bulleuses Auto-immunes, Avicenne Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris, Bobigny, France.
  • Dermatology and Clinical Immunology Department, Centre Hospitalier Universitaire Pointe-à-Pitre and INSERM U1234, Normandie University, Rouen, France.
  • Department of Dermatology-Venereology, Hôpital Robert Debré, Université Reims-Champagne Ardenne, Reims, France.
  • Dermatology Department, Centre Hospitalier Universitaire Dijon, Dijon, France.
  • Department of Dermatology, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France.
  • Department of Dermatology, Centre Hospitalier Lyon Sud, Pierre Bénite, Lyon, France.
  • Department of Dermatology, Hôpital Nord, Assistance Publique-Hôpitaux de Marseille, Aix-Marseille Université, Marseille, France.
  • Department of Dermatology, University of Lille, Lille, France.
  • Department of Dermatology, Centre Hospitalier Départemental Vendée, La Roche-Sur-Yon, France.
  • Department of Dermatology, Centre Hospitalier Universitaire Angers, Angers, France.
  • Department of Dermatology, Assistance Publique des Hôpitaux de Paris, Henri Mondor Hospital, Créteil, France.
  • Univversitaire Paris Est Créteil EpiDermE, Créteil, France.
  • Reference Center MALIBUL, Assistance Publique des Hôpitaux de Paris, Henri Mondor Hospital, Créteil, France.

Abstract

Importance

Rituximab is approved for the treatment of moderate to severe pemphigus. However, 20% of patients in the RITUX 3 trial relapsed within the first year of treatment.

Objective

To assess the outcome of an additional rituximab infusion at month 6 in patients with pemphigus who were in complete remission (CR) after rituximab regimen but had 1 or more predictors of relapse at month 3.

Design, Settings, and Participants

This multicenter cohort study was conducted in France from September 2018 to June 2023 to assess patients with newly diagnosed pemphigus who were in CR after treatment with the RITUX 3 regimen but had predictors of relapse at month 3. Relapse factors were a Pemphigus Disease Area Index (PDAI) score of 45 or higher, desmoglein 1 (DSG1) antibodies greater than 20 IU/mL, and/or DSG3 antibodies greater than 130 IU/mL.

Exposure

Patients in CR at month 6 with at least 1 predictor of relapse were treated with an additional rituximab infusion at month 6.

Main Outcomes and Measures

Primary end point was the rate of CR without corticosteroid therapy for 2 months at month 12. Secondary end points were the rate of relapse, number of patients needing to be re-treated (NNT) with rituximab to avoid a relapse, and safety.

Results

The study population comprised 87 patients (44 females [50.6%] and 43 [49.4%] males), with a mean (SD [range]) age of 55.3 (15.2 [24-92]) years at pemphigus diagnosis. Of these, 64 patients (73.6%) had pemphigus vulgaris and 23 (26.4%) had pemphigus foliaceus. At month 6, CR had been achieved by 77 patients (88.5%), and 10 (11.5%) had persistent disease activity. Of the 77 patients in CR, 30 (39.0%) had at least 1 predictor of relapse and received an additional infusion of rituximab; 47 patients (61.0%) without a predictor did not. Two patients without a predictor and no patients with a predictor experienced relapse-an overall relapse rate of 2.6% and an NNT of 3.6 (95% CI, 1.6-46.5). The 10 patients (11.5%) with persistent disease activity at month 6 were re-treated with rituximab, 2000 mg. At month 12, the rate of CR without corticosteroid therapy for a minimum of 2 months was 72 of 77 (93.5%) among patients who had achieved CR at month 6, and 72 of 87 (82.7%) for the whole study population. Eight serious adverse effects were reported among 5 patients; there were no deaths.

Conclusion and Relevance

This multicenter cohort study indicates that using predictors such as baseline PDAI score, anti-DSG1 antibodies, and/or anti-DSG3 antibodies to initiate preemptive treatment with additional rituximab may reduce the rate of short-term relapse.

MeSH

Antibodies, Adrenal Cortex Hormones, Cohort Studies, Skin Diseases, Rituximab, Therapeutics, Pemphigus

Cited by