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

Rheumatology (Oxford). 2013 Nov;52(11):2041-7. doi: 10.1093/rheumatology/ket257. Epub 2013 Aug 11.


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.

Keywords: ANCA-associated vasculitis; granulomatosis with polyangiitis; hypogammaglobulinaemia; infection; maintenance; rituximab; safety.

MeSH terms

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


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