Cyclophosphamide followed by rituximab for aggressive multiple-relapsing antineutrophil cytoplasmic antibody-associated vasculitis

Objective. To evaluate the long-term outcomes of patients with multi-relapsing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), who received sequentially therapy with cyclophosphamide and rituximab, upon new onset of aggressive vasculitis. Methods. We retrospectively studied patients with multiple-relapsing AAV, who were treated with the standard regimen plus rituximab, given in sequence, upon a major relapse, compared to historical patients, who had been treated with the standard regimen alone in the same setting. The main outcomes of interest were relapse rates and frequency of adverse events. Results. Of 147 patients with biopsy proven AAV, 35 (23.8%) experienced at least one major relapse, of whom, 14 (9.5%) received the sequential regimen and were compared to 21 (14.3%) historic patients, who had received the standard regimen alone for the same reason. Patients in both groups achieved remission in similar rates, but those treated with the sequential regimen experienced a significant decline in the relapse rate afterwards, compared to their corresponding rate prior to study entry [0.07 episodes of relapse per patient-year (95%Cl: 0.03-0.2) vs. 0.38 (95%Cl: 0.35-0.60) respectively, (p=0.004)]. The need for cyclophosphamide was significantly decreased in patients in whom cyclophosphamide was followed by rituximab [3.3(0-10.5) grams vs. 14.5 (4-177) grams, (p<0.0001)] but not in controls [17.2 (0-108) grams vs. 14.5 (0-63) grams, p=0.61]. Conclusion. Our data show that sequential therapy with cyclophosphamide and rituximab, upon a major relapse, in patients with frequently relapsing AAV, is associated with prolonged remission, allowing minimisation of the ultimate exposure to cyclophosphamide.