P0446OUTCOMES OF CYCLOPHOSPHAMIDE FOR ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODIES-ASSOCIATED VASCULITIS: DIFFERENT PROTOCOLS, SINGLE-CENTER EXPERIENCE AND LITERATURE REVIEW
Authors: Agapito Fonseca José , Duarte Inês , Gameiro Joana , Outerelo Cristina , Nogueira Estela , Jorge Sofia , Lopes José António 
Published: June 2020

Abstract

Background and Aims
Cyclophosphamide (CYC), associated with corticosteroids has been considered the mainstay of treatment for severe antineutrophil cytoplasmic antibody−associated vasculitis (AAV) for decades. This protocol is effective in 70-90% of patients resulting in drastic improvement in both renal and patient survival. Nevertheless, cyclophosphamide is associated with significant rates of adverse events, namely severe infections and malignancies. The authors present the single-center experience of the use of CYC for AAV treatment regarding clinical presentation, immunosuppression protocol, outcomes and adverse events, as well as a comparison with the main RCTs and studies using CYC for induction of remission of AAV.

Method
Retrospective analysis of clinical records of patients with AAV diagnosis (de novo or relapse) treated with CYC in the ward of the Nephrology Department of Centro Hospitalar Universitário Lisboa Norte between January 2006 and December 2019.

Results
Thirty patients with AAV diagnosis treated with CYC for induction of remission were identified. Average age was 69.4 ± 11.5 years. On admission, serum creatinine (SCr) was 5.03 mg/dL ± 2.24 mg/dL (eGFR 13.3 mL/min/1.73 m2 ± 11.1 mL/min/1.73 m2). Twenty patients (67%) required renal replacement therapy at admission and 12 (40%) had alveolar hemorrhage. The average Birmingham Vasculitis Activity Score (BVAS) was 27.5 ± 11.5. Immunosuppressive regimens varied considerably, as they were left to the clinician's consideration. Intravenous methylprednisolone pulses were performed in 29 (96.7%) patients, with total dose ranging from 1000 mg to 5000 mg. Cyclophosphamide was also prescribed at clinician’s choice, with only one patient receiving oral CYC and 29 patients receiving from 1 to 11 pulses in different doses. Plasma exchange was performed in 12 (40%) patients due to alveolar hemorrhage and/or rapidly progressive renal insufficiency. After induction of remission, twenty patients received maintenance therapy.
On a 12-month follow-up, 9 (30%) patients were on renal replacement therapy and, in the remaining patients, mean SCr was 2.23 ± 0.98 mg/dL (eGFR 33.4 mL/min/1.73 m2 ± 19.8 mL/min/1.73m2). Fifteen (50%) patients experienced severe infection at 6 months, 3 (10.7%) patients developed malignancies and 7 (23.3%) patients died on a 12-month follow-up.

Conclusion
Our cohort of patients treated with CYC is unlike the population that underwent clinical trials. In our cohort, SCr at presentation was considerably higher, being only comparable to MEPEX and the control arm of RITUXVAS. The BVAS score of our patients was also significantly superior than all other studies. Furthermore, most clinical trials do not include patients with alveolar hemorrhage, present in 40% of the patients in our study, nor RRT requirement, present in 67% of our patients. The higher rate of severe infections and mortality registered in our cohort reflects the severity of the disease at presentation, but also highlights the importance of modifying immunosuppression to the population and the need for future regimens which can reduce the rate of adverse effects.