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

Abstract

ObjectivesTo 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.MethodsNationwide 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.ResultsAmong 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.ConclusionRTX 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.

Remarkable Rituximab Response on Tremor Related to Acute‐Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy in an Antineurofascin155 Immunoglobulin G4–Seropositive Patient

“…Rituximab seemed effective as both induction and maintenance therapy. In IgG4‐related diseases, relapses are frequent after B‐cell reconstitution . In line with these experiences, our report suggests that titrating rituximab to circulating B cells might be effective in preventing relapses.…”

Predicting Severe Infection and Effects of Hypogammaglobulinemia During Therapy With Rituximab in Rheumatic and Musculoskeletal Diseases

“…Rituximab (RTX) has been licensed for use as a treatment for moderate‐to‐severe rheumatoid arthritis (RA) for more than a decade as well as approved for remission induction of antineutrophil cytoplasmic antibody–associated vasculitis (AAV) . Despite the failure of randomized controlled trials (RCTs) in meeting their primary end points in systemic lupus erythematosus (SLE) , primary Sjögren's syndrome (SS) and inflammatory myopathies , RTX is commonly used off‐label in these indications and other various rheumatic and musculoskeletal diseases (RMDs), often in cases that are refractory to other systemic therapies . However, the immunomodulatory properties of biologic disease‐modifying antirheumatic drugs (bDMARDs) in general, including RTX, have raised safety concerns, prompting careful evaluation in RCTs and intensive surveillance after marketing .…”

Immunoglobulin G4 related disease: a single‐centre experience from South Australia

“…Oral glucocorticoids are first‐line therapy and highly effective in the majority of patients. Relapses are common, requiring the use of steroid sparing agents and in some occasions B‐cell depletion therapy …”