Long-term efficacy and safety of pre-emptive maintenance therapy with rituximab in granulomatosis with polyangiitis: Results from a single centre

Rheumatology, Institute of Clinical Medicine, University of Tromsø, Rheumatology, University Hospital of North Norway, Tromsø, Norway and Division of Medicine, Royal Darwin Hospital, Department of Health, Darwin, Northern Territory, Australia.
Rheumatology (Oxford, England) (Impact Factor: 4.48). 08/2013; 52(11). DOI: 10.1093/rheumatology/ket257
Source: PubMed


Rituximab (RTX) is an anti-CD20 antibody used successfully in granulomatosis with polyangiitis (GPA) for induction and maintenance of remission. Our study aims to evaluate the long-term efficacy and safety of chronic pre-emptive RTX therapy in GPA.

Retrospective study of 35 GPA patients treated with RTX between April 2004 and September 2011 for active disease and maintenance. RTX was initiated as two 1 g infusions 2 weeks apart and thereafter 2 g of RTX was readministered annually. Patients were followed for 47 (2-88) months. They received a median RTX dose of 8 g (2-13) over 5 (1-10) rounds.

All patients had a clinical response, but nine relapses were recorded (flare rate of 6.6/100 patient-years). At last visit, 13 patients (37%) had discontinued RTX mainly due to hypogammaglobulinaemia (57%). Nine patients (26%) had severe infections (infection rate of 6.6/100 patient-years) and 10 patients (29%) had chronic infections. Risks factors for severe infections are a high cumulative dose of CYC, low CD4 cell count and a significant drop in total immunoglobulins after the first RTX round. Risks factors for chronic infections are low IgG level during RTX maintenance and possibly the cumulative RTX dose.

Long-term pre-emptive RTX maintenance was efficacious in reducing the risk for relapse but was discontinued in one-third of the patients. The patients' net state of immunodeficiency under RTX changes over time as low immunoglobulin serum levels increased the risk for infections.

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    • "Retrospective data supports the use of repeated dosing with rituximab every 6 months for 2 years to maintain remission, with relapse rates of only 12 % during 24 months of treatment [168]. There is, however, a risk of hypogammaglobulinaemia associated with long term treatment with rituximab [169]. Randomised studies of rituximab versus azathioprine as maintenance therapy are ongoing. "
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