• Victoria P Werth, Pascal Joly, Daniel Mimouni, Emanual Maverakis, Frédéric Caux, Patricia Lehane, Liudmila Gearhart, Audrey Kapre, Pooneh Pordeli, Diana M Chen, and PEMPHIX Study Group.
• From the Perelman School of Medicine, University of Pennsylvania, and the Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia (V.P.W.); the Department of Dermatology, Rouen University Hospital and INSERM 1234, Normandie Université, Rouen (P.J.), and the Department of Dermatology, Groupe Hospitalier Paris Seine-Saint-Denis, Assistance Publique-Hôpitaux de Paris and INSERM Unité Mixte de Recherche 1125, Bobigny (F.C.) - all in France; the Sackler School of Medicine, Tel Aviv University, Tel Aviv, and Rabin Medical Center, Petah Tikva - both in Israel (D.M.); the Department of Dermatology, University of California, Davis, School of Medicine, Sacramento (E.M.), and Genentech, South San Francisco (A.K., D.M.C.) - both in California; Roche Products, Welwyn Garden City, United Kingdom (P.L.); F. Hoffmann-La Roche, Basel, Switzerland (L.G.); and Roche Products, Mississauga, ON, Canada (P.P.).
• N. Engl. J. Med. 2021 Jun 17; 384 (24): 2295-2305.

BackgroundRituximab and mycophenolate mofetil are used to treat pemphigus vulgaris, but they have not been adequately compared in clinical trials.MethodsIn a randomized, controlled trial, we assigned patients with moderate-to-severe pemphigus vulgaris in a 1:1 ratio to receive intravenous rituximab (1000 mg on days 1, 15, 168, and 182) or oral mycophenolate mofetil (2 g per day), in addition to an oral glucocorticoid administered on the same tapering schedule in the two groups. The primary end point was sustained complete remission at week 52, defined as the healing of lesions with no new active lesions, as reflected by a Pemphigus Disease Area Index (PDAI) activity score of 0 (on a scale of 0 to 250, with higher scores indicating greater disease severity), for at least 16 weeks without the use of glucocorticoids. Secondary end points were the cumulative dose of glucocorticoids, the number of disease flares, and the change from baseline in the score on the Dermatology Life Quality Index (DLQI; scores range from 0 to 30, with higher scores indicating greater impairment).ResultsOf the 135 patients who underwent randomization, 67 were assigned to receive rituximab and 68 to receive mycophenolate mofetil. The primary outcome was assessed in the modified intention-to-treat population: 62 patients in the rituximab group and 63 in the mycophenolate mofetil group. The median PDAI activity scores at baseline were 22.7 in the rituximab group and 18.3 in the mycophenolate mofetil group. At week 52, sustained complete remission was observed in 25 patients (40%) in the rituximab group and in 6 (10%) in the mycophenolate mofetil group (difference, 31 percentage points; 95% confidence interval [CI], 15 to 45; P<0.001). The mean cumulative glucocorticoid dose during the 52-week treatment period was 3545 mg in the rituximab group and 5140 mg in the mycophenolate mofetil group (difference, -1595 mg; 95% CI, -2838 to -353; P<0.001). There were 6 disease flares in the rituximab group and 44 in the mycophenolate mofetil group (adjusted rate ratio, 0.12; 95% CI, 0.05 to 0.29; P<0.001). The mean change in DLQI score was -8.87 points and -6.00 points, respectively (difference, -2.87 points; 95% CI, -4.58 to -1.17; P = 0.001). Serious adverse events occurred in 15 of 67 patients (22%) in the rituximab group and in 10 of 68 (15%) in the mycophenolate mofetil group.ConclusionsRituximab was superior to mycophenolate mofetil in producing sustained complete remission at 52 weeks in patients with pemphigus vulgaris. Rituximab resulted in a greater reduction in glucocorticoid use than mycophenolate mofetil, but more patients in the rituximab group had serious adverse events. Further trials are needed to determine the comparative efficacy and safety of rituximab and mycophenolate mofetil beyond 52 weeks of treatment. (Funded by F. Hoffmann-La Roche; PEMPHIX ClinicalTrials.gov number, NCT02383589.).Copyright © 2021 Massachusetts Medical Society.

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