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

Abstract

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Emilio Besada, Wenche Koldingsnes, Johannes C Nossent
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 52 Issue 11 Pg. 2041-7 (Nov 2013) ISSN: 1462-0332 [Electronic] England
• PMID: 23934313 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Immunosuppressive Agents
• Rituximab

Topics

• Adolescent
• Adult
• Aged
• Antibodies, Monoclonal, Murine-Derived (administration & dosage, adverse effects, therapeutic use)
• CD4 Lymphocyte Count
• Drug Administration Schedule
• Drug Evaluation (methods)
• Female
• Granulomatosis with Polyangiitis (complications, drug therapy, immunology)
• Humans
• Immunocompromised Host
• Immunosuppressive Agents (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Opportunistic Infections (complications, immunology)
• Remission Induction
• Retrospective Studies
• Risk Factors
• Rituximab
• Treatment Outcome
• Young Adult