Long-term outcomes of daily oral vs. pulsed intravenous cyclophosphamide in a non-trial setting in ANCA-associated vasculitis

Abstract

We aimed to compare risk of death, relapse, neutropenia and infection requiring hospital admission between unselected ANCA-associated vasculitis (AAV) patients according to whether cyclophosphamide induction was by daily oral (PO) or pulse intravenous (IV) route. We identified all newly diagnosed AAV patients treated with PO or IV cyclophosphamide between March 2007 and June 2013. We used Cox and logistic regression models to compare mortality, relapse and adverse events and adjusted these for age, renal function and other significant confounders. Fifty-seven patients received PO and 57 received IV cyclophosphamide. One-year survival was 86.0% in PO and 98.2% in IV patients; all-time adjusted hazard ratio (HR) for PO compared to that of IV cyclophosphamide was 1.8 (95% CI 0.3–10.6, P = 0.54). One-year relapse-free survival was 80.7% in PO compared to 87.3% in IV patients, all-time adjusted HR 3.8 (0.2–846, P = 0.37). During the first 12 months, neutropenia of ≤ 0.5 × 109/L occurred in 9 (16%) PO and 0 (0%) IV cyclophosphamide patients (P = 0.003). The number of patients admitted with one or more infections was 16 (28%) in the PO group and 9 (16%) in the IV group, adjusted OR 2.2 (0.6–8.6, P = 0.23). We observed an increased risk of neutropenia, a trend towards increased risk of death and an admission with infection with PO cyclophosphamide. This adds certainty to previous studies, indicating that PO administration induces greater marrow toxicity. Infection-related admissions within 12 months of starting cyclophosphamide were higher than those in clinical trials, possibly reflecting the unselected nature of this cohort.

Outcomes and compliance with standards of care in anti-neutrophil cytoplasmic antibody–associated vasculitis—insights from a large multiregion audit

“…Based on these exclusion criteria alone, 7% of the patients included in our audit would have been excluded from the CYCLOPS trial. Our results are similar to a recent study of all patients presenting to a single centre, where 22% of patients receiving CYC for AAV were admitted with infection during the first year after commencing treatment [19]. This suggests 22–25% may be a realistic estimate of the risk of hospitalisation with infection in the year after starting CYC and patients should receive counselling about pre-treatment.…”

Granulomatosis with Polyangiitis in Adolescence: Two Distinct Presentations

“…Intravenously Cyp reduces cumulative exposure and seems to be associated with fewer side effects, such as leukopenia and neutropenia, compared to oral Cyp. Nevertheless, there is also a considerable number of Cyp nonresponders or frequent relapses and progression of the disease [17][18][19]. Rituximab, a monoclonal antibody that targets B cells, has been used in both induction-remission and maintenance therapy, particularly in young patients, with good results in comparison to cyclophosphamide, as shown in RAVE and RITUXVAS Trials [20][21][22].…”

Infection-related hospitalization after intensive immunosuppressive therapy among lupus nephritis and ANCA glomerulonephritis patients

“…In addition, the infection rate became even higher with the usage of glucocorticoids and immunosuppressive agents [14,28]. Goupil et al reported that the infection rate of ANCA-associated vasculitis was 53% [23], and other studies indicated that the rate of infection requiring admission to the hospital in these patients was 21.9-46.2% after intensive immunosuppressive therapy [16,17,29,30]. In the current study, we found that 33.4% of LN patients had IRH after intensive immunosuppressive therapy, similar to the results of previous studies [31][32][33].…”

“…Undoubtedly, the risk of treatment-related infection is increased due to the combined use of glucocorticoid and immunosuppressive agents, which would inhibit the immune function of the patients [9][10][11][12]. Moreover, infection among LN and ANCA glomerulonephritis patients was suggested to be a leading cause of rehospitalization and mortality and was associated with a significant economic and social burden [13][14][15][16][17]. In clinical practice, we noticed that the infection rates seemed to be higher and the outcomes seemed to be poorer in patients with ANCA glomerulonephritis than in patients with LN after intensive immunosuppressive therapy, but this observation had not been rigorously investigated.…”