Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients

Mikael Ebbo (1) , Aurelie Grados (1) , Maxime Samson (2) , Matthieu Groh (3, 4, 5) , Anderson Loundou (6, 7) , Pierre Rigolet (8, 8) , Benjamin Terrier (3, 4, 5) , Constance Guillaud (9) , Clarisse Carra-Dallière (10) , Frédéric Renou (11) , Agnieszka Pozdzik , Pierre Labauge (10, 12) , Sylvain Palat (13) , Jean-Marie Berthelot (14) , Jean-Loup Pennaforte (15) , Alain Wynckel (15) , Céline Lebas (16) , Noémie Le Gouellec (17) , Thomas Quemeneur (17) , Karine Dahan (18) , Franck Carbonnel (19) , Gaëlle Leroux (8, 8) , Antoinette Perlat (20) , Alexis Mathian (8, 8) , Patrice Cacoub (8, 8) , Eric Hachulla (21) , Nathalie Costedoat-Chalumeau (3, 4, 5) , Jean-Robert Harlé (1) , Nicolas Schleinitz (1)

1 TIMONE - Hôpital de la Timone [CHU - APHM]
2 Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon]
3 Service de médecine interne et centre de référence des maladies rares [CHU Cochin]
4 UPD5 - Université Paris Descartes - Paris 5
5 USPC - Université Sorbonne Paris Cité
6 APHM - Assistance Publique - Hôpitaux de Marseille
7 AMU - Aix Marseille Université
8 CHU Pitié-Salpêtrière [AP-HP]
9 Service de médecine interne [Mondor]
10 Département de neurologie [Montpellier]
11 CHU La Réunion - Centre Hospitalier Universitaire de La Réunion
12 UM - Université de Montpellier
13 Service de Médecine interne A et polyclinique médicale [CHU Limoges]
14 Service de rhumatologie [Nantes]
15 Hôpital universitaire Robert Debré [Reims]
16 Service de Néphrologie et Transplantation rénale [CHRU-lille]
17 Centre hospitalier [Valenciennes, Nord]
18 CHU Tenon [AP-HP]
19 Hôpital Bicêtre
20 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
21 Hôpital Claude Huriez [Lille]

Objectives: To assess efficacy and safety of rituximab (RTX) as induction therapy, maintenance of remission and treatment of relapses in a cohort of IgG4-related disease (IgG4-RD) patients. Methods: Nationwide retrospective multicenter study of IgG4-RD patients treated with at least one course of RTX. Clinical, biological and radiological response, relapse rate and drug tolerance were analyzed. Kaplan-Meier curves were plotted and risk factors for relapse studied with a Cox regression model. Results: Among 156 IgG4-RD patients included in the French database, 33 received rituximab. Clinical response was noted in 29/31 (93.5%) symptomatic patients. Glucocorticoids withdrawal was achieved in 17 (51.5%) patients. During a mean follow-up of 24.8 ±21 months, 13/31 (41.9%) responder patients relapsed after a mean delay of 19 ±11 months after RTX. Active disease, as defined by an IgG4-RD Responder Index >9 before RTX, was significantly associated with relapse (HR = 3.68, 95% CI: 1.1, 12.6) (P = 0.04), whereas maintenance therapy with systematic (i.e. before occurrence of a relapse) RTX retreatment was associated with longer relapse-free survival (41 versus 21 months; P = 0.02). Eight severe infections occurred in 4 patients during follow-up (severe infections rate of 12.1/100 patient-years) and hypogammaglobulinemia ≤5 g/l in 3 patients. Conclusion: RTX is effective for both induction therapy and treatment of relapses in IgG4-RD, but relapses are frequent after B-cell reconstitution. Maintenance therapy with systematic RTX infusions is associated with longer relapse-free survival and might represent a novel treatment strategy. Yet, the high rate of infections and the temporary effect of RTX might be hindrances to such strategy.

Mots clés: Drug therapy; T cells; Lesions; Magnetic resonance imaging; B cells; Diagnostic medicine; Radiology and imaging; Fibrosis

Domaines: Immunothérapie

Mikael Ebbo, Aurelie Grados, Maxime Samson, Matthieu Groh, Anderson Loundou, et al.. Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients. PLoS ONE, 2017, 12 (9), pp.e0183844. ⟨10.1371/journal.pone.0183844⟩. ⟨hal-01745918⟩