Henderson, S; Copley, S; Pusey, CD; Ind, PW; Salama, AD; (2014) Prolonged B Cell Depletion with Rituximab is Effective in Treating Refractory Pulmonary Granulomatous Inflammation in Granulomatosis with Polyangiitis. Medicine , 93 (27) , Article e229. 10.1097/MD.0000000000000229.

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Abstract

Objective - Pulmonary nodule formation is a frequent feature of granulomatosis with polyangiitis (GPA). Traditional induction therapy includes methotrexate or cyclophosphamide, however, pulmonary nodules generally respond slower than vasculitic components of disease. Efficacy of rituximab (RTX) solely for the treatment of pulmonary nodules has not been assessed. In this observational cohort study, we report patient outcomes with RTX in GPA patients with pulmonary nodules who failed to achieve remission following conventional immunosuppression. Methods - Patients (n = 5) with persistent pulmonary nodules were identified from our clinic database and retrospectively evaluated. Systemic manifestations, inflammatory markers, disease activity, concurrent immunosuppression and absolute B cell numbers were recorded pre-RTX and at 6 monthly intervals following treatment. Chest radiographs at each time point were scored by an experienced radiologist, blinded to clinical details. Results - Five patients with GPA and PR3-ANCA were evaluated (2 male, 3 female), mean age 34 (22-52) years. Pulmonary nodules (median 4, range 2-6), with or without cavitation were present in all patients. RTX induced initial B cell depletion (< 5 cells/µl) in all patients but re-population was observed in 3 patients. Repeated RTX treatment in these three and persistent B cell depletion in the whole cohort was associated with further significant radiological improvement. Radiographic scoring at each time interval showed reduction in both number of nodules (p = <0.0001) and largest nodule diameter (p = <0.0001) in all patients for at least 18 months following B cell depletion. Conclusion - RTX therapy induces resolution of pulmonary granulomatous inflammation in GPA following prolonged B cell depletion.

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