Background/Purpose: IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition with characteristic histopathological lesions. Nearly all anatomic sites can be involved with a risk of organ dysfunction. A dramatic response to steroids is usual but relapses are frequent and steroids sparing agents are frequently required. Favorable response to B-cell depletion by rituximab (RTX) has been suggested by case reports, small series and an open label trial. However data “in real life” with a long term follow-up are sparse, especially concerning the efficacy and tolerance. We analyzed rituximab use in a national multicentric cohort of IgG4-RD patients.

Methods: Patients included in a national multicentric cohort of IgG4-related disease and treated by RTX were included in this study. All patients fulfilled the 2011 comprehensive IgG4-RD diagnostic (CDC) criteria. All differential diagnosis were systematically ruled out. Clinical, biological, histological, radiological and therapeutic data were retrospectively collected in order to evaluate efficacy and tolerance of RTX in this indication.

Results: Twenty-four patients were included in this study. All patients fulfilled the 2011 CDC criteria, with a “definite” diagnosis in 15 cases, “probable” in 6 cases and “possible” in 3 patients. Median age at RTX was 57 years [extreme 36-84]. Median duration of the disease before RTX was 35.5 months [4-180], and mean number of previous medical treatments was 1.6 [0-4], with previous steroid use in all patients but one. Median number of organ involved was 5 [1-8], and organ involvement justifying use of RTX was mainly kidney in 6 patients (25%), biliary involvement in 6 (25%), pancreas in 5 (21%), retroperitoneal and/or aortic involvement in 4 (15%). Administration was 1gx2 d1-d15 in most patients (63%), and 375 mg/m2 in 6 (25%). A clinical efficacy was noted in 18/22 patients symptomatic at treatment initiation. A decrease of IgG4 serum levels was observed 13/14 evaluable patients with pre-treatment serum IgG4 elevation. Imagery (conventional and/or metabolic) improvement was noted in 12/18 and stability was noted in 5 over 18 evaluable patients. Among 21 responders, 7 patients (33%) presented a relapse, with a median follow-up of 11 months [1-129]. Relapse occurred with a median delay of 18 months [9-36] after RTX treatment. Corticosteroids could be stopped in only 12/23 evaluable patients (52%). Infectious events were observed in 10 patients (42%), with severe infections in 2 patients with concomitant steroid therapy (septic shock in 1, and mitral endocarditis in 1). Hypogammaglobulinemia was observed in 2 patients, requiring immunoglobulin substitution in one case.

Conclusion: Rituximab appear to be effective in more than 80% of patients with IgG4-RD. Nevertheless, complete withdrawal of steroids was possible in only half of patients. One third of patients relapsed after 1 year of follow-up. Finally, infectious events and hypogammaglobulinemia are not rare and must be monitored, even if the responsibility of RTX is difficult to assess in these multitreated patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-tolerance-of-rituximab-in-igg4-related-disease-a-retrospective-multicentric-study-in-24-patients/