Rituximab for induction and maintenance therapy in granulomatosis with polyangiitis (Wegener's). Results of a single-center cohort study on 66 patients

• Published in: Journal of autoimmunity Vol. 50; pp. 135 - 141
• Main Authors: Calich, Ana Luisa, Puéchal, Xavier, Pugnet, Grégory, London, Jonathan, Terrier, Benjamin, Charles, Pierre, Mouthon, Luc, Guillevin, Loïc
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.05.2014; Elsevier
• Subjects: Adult; Aged; Allergy and Immunology; ANCA-associated vasculitis; Antibodies, Monoclonal, Murine-Derived - therapeutic use; Biological and medical sciences; Drug Administration Schedule; Drug Monitoring; Drug Therapy, Combination; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glucocorticoids; Glucocorticoids - therapeutic use; Granulomatosis with polyangiitis; Granulomatosis with Polyangiitis - drug therapy; Granulomatosis with Polyangiitis - immunology; Granulomatosis with Polyangiitis - pathology; Humans; Immunologic Factors - therapeutic use; Maintenance; Male; Medical sciences; Middle Aged; Prednisone - therapeutic use; Recurrence; Remission Induction; Remission induction treatment; Retrospective Studies; Rituximab; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Severity of Illness Index; Granulomatosis with polyangiitis; Rituximab; Maintenance; Glucocorticoids; Remission induction treatment; ANCA-associated vasculitis; Human; Antineutrophil cytoplasmic antibody; Granulomatosis; Cardiovascular disease; Monoclonal antibody; Glucocorticoid; Induction treatment; Vascular disease; Immunology; Vasculitis; Cohort study; Immunotherapy; Maintenance treatment; Remission
• ISSN: 0896-8411; 1095-9157; 1095-9157
• DOI: 10.1016/j.jaut.2014.03.002

The aim of this study was to evaluate the efficacy and safety of rituximab (RTX) associated with glucocorticoid treatment based on disease severity, as a remission induction treatment for granulomatosis with polyangiitis (GPA) (Wegener's) and to analyze the results of long-term maintenance therapy with low doses of RTX in a routine time-based protocol. This single-center retrospective study used standardized data collection from all GPA patients receiving RTX between 2002 and 2013. The remission induction regimen consisted of RTX and glucocorticoids, adapted according to disease severity. Once remission was achieved, patients received RTX maintenance treatment (500 mg every 6 months) for 18 months. Sixty-six GPA patients received RTX for remission induction. After six months, a response had been achieved in 78.8% of these patients, with a moderate oral prednisone regimen (mean dose at baseline, 32.8 ± 23.4 mg/day). Subglottic stenosis increased the risk of treatment failure (OR = 31.2, P = 0.0104). RTX maintenance treatment was continued for 18 months in 92% of the GPA patients, who were followed for 34.2 ± 26.2 months (mean total cumulative RTX dose of 4.6 ± 1.7 g). The relapse rate was 11.2/100 patient-years. The relapses occur a mean of 13.5 ± 14.7 months after the last RTX infusion. Twenty-one severe adverse events were recorded; 13.6% patients had severe infections. We conclude that in this single-center cohort, RTX associated with glucocorticoid treatment adapted for disease severity appeared to induce remission effectively in GPA patients. Maintenance treatment with low doses of RTX in a routine time-based protocol was safe and associated with low rates of relapse on treatment. •This is a long follow-up study of a single-center cohort of patients with granulomatosis with polyangiitis (Wegener's).•Rituximab was effective for remission induction and maintenance therapy, despite low doses of steroids and rituximab.•Low-dose rituximab in a routine time-based protocol for maintenance therapy appears to be effective with low toxicity.