PMID- 31487383 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20231111 IS - 1365-2133 (Electronic) IS - 0007-0963 (Print) IS - 0007-0963 (Linking) VI - 182 IP - 5 DP - 2020 May TI - Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect. PG - 1111-1119 LID - 10.1111/bjd.18482 [doi] AB - BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0.5 or 1.0 mg kg(-1) per day prednisone tapered over 3 or 6 months, or 1.0 or 1.5 mg kg(-1) per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for >/= 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff >/= 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV. CI - (c) 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists. FAU - Chen, D M AU - Chen DM AD - Genentech, Inc., South San Francisco, CA, U.S.A. FAU - Odueyungbo, A AU - Odueyungbo A AD - Roche Products Ltd, Mississauga, ON, L5N 5M8, Canada. FAU - Csinady, E AU - Csinady E AD - F. Hoffmann-La Roche, Basel, Switzerland. FAU - Gearhart, L AU - Gearhart L AD - F. Hoffmann-La Roche, Basel, Switzerland. FAU - Lehane, P AU - Lehane P AD - Roche Products Ltd, Welwyn Garden City, AL7 1TW, U.K. FAU - Cheu, M AU - Cheu M AD - Genentech, Inc., South San Francisco, CA, U.S.A. FAU - Maho-Vaillant, M AU - Maho-Vaillant M AD - Department of Dermatology, Rouen University Hospital and INSERM U 1234, National Reference Centre on Autoimmune Bullous Disease, Normandy University, 76000, Rouen, France. FAU - Prost-Squarcioni, C AU - Prost-Squarcioni C AD - Department of Biostatistics, Rouen University Hospital and INSERM U1181, National Reference Centre on Autoimmune Bullous Disease, Normandy University, 76000, Rouen, France. FAU - Hebert, V AU - Hebert V AD - Department of Dermatology, Rouen University Hospital and INSERM U 1234, National Reference Centre on Autoimmune Bullous Disease, Normandy University, 76000, Rouen, France. FAU - Houivet, E AU - Houivet E AD - Department of Dermatology, Avicenne Hospital and INSERM UMR1125, Paris 13 University, 93000, Bobigny, France. FAU - Calbo, S AU - Calbo S AD - Department of Dermatology, Rouen University Hospital and INSERM U 1234, National Reference Centre on Autoimmune Bullous Disease, Normandy University, 76000, Rouen, France. FAU - Caillot, F AU - Caillot F AD - Department of Dermatology, Rouen University Hospital and INSERM U 1234, National Reference Centre on Autoimmune Bullous Disease, Normandy University, 76000, Rouen, France. FAU - Golinski, M L AU - Golinski ML AD - Department of Dermatology, Rouen University Hospital and INSERM U 1234, National Reference Centre on Autoimmune Bullous Disease, Normandy University, 76000, Rouen, France. FAU - Labeille, B AU - Labeille B AD - Department of Dermatology, University of Saint Etienne, 42023, Saint Etienne, France. FAU - Picard-Dahan, C AU - Picard-Dahan C AD - Department of Dermatology, Bichat - Claude Bernard Hospital, 75018, Paris, France. FAU - Paul, C AU - Paul C AD - Department of Dermatology, University of Toulouse, 31013, Toulouse, France. FAU - Richard, M A AU - Richard MA AD - Department of Dermatology, Assistance Publique des Hopitaux de Marseille, Aix Marseille University, UMR 911, INSERM CRO2, 13007, Marseille, France. FAU - Bouaziz, J D AU - Bouaziz JD AD - Department of Dermatology of Saint Louis Hospital, Paris 7 Sorbonne Paris Cite University, 75010, Paris, France. FAU - Duvert-Lehembre, S AU - Duvert-Lehembre S AD - Department of Dermatology, Rouen University Hospital and INSERM U 1234, National Reference Centre on Autoimmune Bullous Disease, Normandy University, 76000, Rouen, France. FAU - Bernard, P AU - Bernard P AD - Department of Dermatology, University of Reims, 51100, Reims, France. FAU - Caux, F AU - Caux F AD - Department of Biostatistics, Rouen University Hospital and INSERM U1181, National Reference Centre on Autoimmune Bullous Disease, Normandy University, 76000, Rouen, France. FAU - Alexandre, M AU - Alexandre M AD - Department of Biostatistics, Rouen University Hospital and INSERM U1181, National Reference Centre on Autoimmune Bullous Disease, Normandy University, 76000, Rouen, France. FAU - Ingen-Housz-Oro, S AU - Ingen-Housz-Oro S AD - Department of Dermatology, APHP, Henri Mondor Hospital, 94010, Creteil, France. FAU - Vabres, P AU - Vabres P AD - Department of Dermatology, Dijon University Hospital, 21079, Dijon, France. FAU - Delaporte, E AU - Delaporte E AD - Department of Dermatology, University of Lille and Claude-Huriez Hospital, 59037, Lille, France. FAU - Quereux, G AU - Quereux G AD - Department of Dermatology, University of Nantes, 44035, Nantes, France. FAU - Dupuy, A AU - Dupuy A AD - Department of Dermatology, University of Rennes, 35042, Rennes, France. FAU - Debarbieux, S AU - Debarbieux S AD - Department of Dermatology, Centre Hospitalier Lyon Sud, 69310, Pierre Benite, France. FAU - Avenel-Audran, M AU - Avenel-Audran M AD - Department of Dermatology, University of Angers, 49035, Angers, France. FAU - D'Incan, M AU - D'Incan M AD - Department of Dermatology, University of Clermont-Ferrand, 63001, Clermont-Ferrand, France. FAU - Bedane, C AU - Bedane C AD - Department of Dermatology, University of Limoges, 87032, Limoges, France. FAU - Beneton, N AU - Beneton N AD - Department of Dermatology, Le Mans General Hospital, 72037, Le Mans, France. FAU - Jullien, D AU - Jullien D AD - Department of Dermatology, Edouard Herriot Hospital, Lyon Claude Bernard University, 69003, Lyon, France. FAU - Dupin, N AU - Dupin N AD - Department of Dermatology, Cochin Hospital, University of Paris V, 75006, Paris, France. FAU - Misery, L AU - Misery L AD - Department of Dermatology and, Brest University Hospital, 29200, Brest, France. FAU - Machet, L AU - Machet L AD - Department of Dermatology, Tours University Hospital, 37044, Tours, France. FAU - Beylot-Barry, M AU - Beylot-Barry M AD - Department of Dermatology, University of Bordeaux, 33076, Bordeaux, France. FAU - Dereure, O AU - Dereure O AD - Department of Dermatology, University of Montpellier, 34090, Montpellier, France. FAU - Sassolas, B AU - Sassolas B AD - Department of Internal Medicine, Brest University Hospital, 29200, Brest, France. FAU - Benichou, J AU - Benichou J AD - Department of Dermatology, Avicenne Hospital and INSERM UMR1125, Paris 13 University, 93000, Bobigny, France. FAU - Musette, P AU - Musette P AD - Department of Dermatology, Rouen University Hospital and INSERM U 1234, National Reference Centre on Autoimmune Bullous Disease, Normandy University, 76000, Rouen, France. FAU - Joly, P AU - Joly P AD - Department of Dermatology, Rouen University Hospital and INSERM U 1234, National Reference Centre on Autoimmune Bullous Disease, Normandy University, 76000, Rouen, France. CN - French Study Group on Autoimmune Bullous Diseases LA - eng GR - Genentech/International PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20191128 PL - England TA - Br J Dermatol JT - The British journal of dermatology JID - 0004041 RN - 0 (Immunologic Factors) RN - 0 (Immunosuppressive Agents) RN - 4F4X42SYQ6 (Rituximab) RN - VB0R961HZT (Prednisone) SB - IM CIN - Br J Dermatol. 2020 May;182(5):1078-1079. PMID: 31957012 MH - Humans MH - Immunologic Factors/adverse effects MH - Immunosuppressive Agents/adverse effects MH - *Pemphigus/drug therapy MH - Prednisone MH - Rituximab/adverse effects MH - Treatment Outcome PMC - PMC7317434 EDAT- 2019/09/06 06:00 MHDA- 2021/05/15 06:00 PMCR- 2020/06/26 CRDT- 2019/09/06 06:00 PHST- 2019/08/29 00:00 [accepted] PHST- 2019/09/06 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2019/09/06 06:00 [entrez] PHST- 2020/06/26 00:00 [pmc-release] AID - BJD18482 [pii] AID - 10.1111/bjd.18482 [doi] PST - ppublish SO - Br J Dermatol. 2020 May;182(5):1111-1119. doi: 10.1111/bjd.18482. Epub 2019 Nov 28.