Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): comparison of efficacy in granulomatous versus vasculitic manifestations
- Julia U Holle1,
- Christin Dubrau1,
- Karen Herlyn1,
- Martin Heller2,
- Petra Ambrosch3,
- Bernhard Noelle4,
- Eva Reinhold-Keller1,
- Wolfgang L Gross1
- 1Department of Rheumatology and Clinical Immunology, Vasculitis Center, University Hospital Schleswig-Holstein, Campus Lübeck and Klinikum Bad Bramstedt, Bad Bramstedt, Germany
- 2Department of Diagnostic Radiology, University of Kiel, Kiel, Germany
- 3Department of Otorhinolaryngology, University of Kiel, Kiel, Germany
- 4Department of Ophthalmology, University of Kiel, Kiel, Germany
- Correspondence to Dr Julia U Holle, Department of Rheumatology and Clinical Immunology, Vasculitis Center, University Hospital Schleswig-Holstein/Klinikum Bad Bramstedt, Oskar-Alexander-Strasse 26, 24576 Bad Bramstedt, Germany;
- Received 12 March 2011
- Accepted 14 August 2011
- Published Online First 21 October 2011
Objective First, to investigate the overall efficacy and safety of rituximab (RTX) in refractory granulomatosis with polyangiitis (GPA) in a tertiary referral centre. Second, to compare the efficacy of RTX in granulomatous and vasculitic manifestations in GPA.
Patients and methods This study comprised a retrospective, standardised data collection from all patients who received RTX for refractory Wegener's granulomatosis from 2002 to 2010. Patients were assessed by a standardised interdisciplinary diagnostic procedure (including ear, nose and throat and ophthalmology assessment, MRI, immunodiagnostics, B-cell levels and Birmingham Vasculitis Activity Score) and were treated by standardised therapeutic regimens according to available evidence.
Results 59 patients received 75 cycles of RTX. 9.3% achieved complete remission. A response was documented in 61.3% (improvement in 52%, unchanged disease activity in 9.3%), 26.7% had refractory disease. Birmingham Vasculitis Activity Score, disease extent index, erythrocyte sedimentation rate, C-reactive protein and prednisolone demand decreased significantly. All patients achieved B-cell depletion. Granulomatous manifestations such as orbital granuloma and pachymeningitis were more frequently refractory to RTX than vasculitis or other granulomatous manifestations. Thus, for example, complete remission/improvement was found in 89.2% of patients with renal disease and in only 44.4% of those with orbital masses (p=0.003). The relapse rate was 44.4% after a median period of 13.5 months. Adverse events occurred in 29%, pneumonia in 15% and death in 3%.
Conclusion The overall response rate of refractory GPA to RTX was high (61.3% complete remission or improvement). Response rates of vasculitic manifestations were excellent; failure of response/progress was mostly due to granulomatous manifestations, especially orbital masses. Relapse rates were high (40%) despite maintenance treatment.
Competing interests None.
Ethics approval Ethics approval was obtained from University of Luebeck.
Provenance and peer review Not commissioned; externally peer reviewed.