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Clinical Trial
. 2017 Sep 15;12(9):e0183844.
doi: 10.1371/journal.pone.0183844. eCollection 2017.

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

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

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

Mikael Ebbo et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Kaplan-Meier plots of the risk of disease relapse following rituximab in 31 IgG4-RD responding patients.
Fig 2
Fig 2. Kaplan-Meier plots of the risk of disease relapse following rituximab for patients with IgG4-RD RI >9 and with IgG4-RD RI ≤9 at RTX treatment.
IgG4-RD RI, IgG4-related disease Responder Index.
Fig 3
Fig 3. Risk of disease relapse following rituximab for patients with glucocorticoid and without glucocorticoid maintenance therapy at last follow-up or relapse.
Fig 4
Fig 4. Risk of disease relapse for patients with or without “prophylactic” maintenance therapy with rituximab.
See this image and copyright information in PMC

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