Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up
- Lorraine Harper1,
- Matthew D Morgan1,
- Michael Walsh2,
- Peter Hoglund3,
- Kerstin Westman4,
- Oliver Flossmann5,
- Vladimir Tesar6,
- Phillipe Vanhille7,
- Kirsten de Groot8,
- Raashid Luqmani9,
- Luis Felipe Flores-Suarez10,
- Richard Watts11,
- Charles Pusey12,
- Annette Bruchfeld13,
- Niels Rasmussen14,
- Daniel Blockmans15,
- Caroline O Savage1,
- David Jayne1 on behalf of EUVAS investigators
- 1School of Immunity and Infection, University of Birmingham, Birmingham, UK
- 2Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada
- 3Competence Centre for Clinical Research, Skane University Hospital, Lund, Sweden
- 4Department of Nephrology and Transplantation, Skane University Hospital Malmö, Lund University, Sweden
- 5Department of Nephrology, Royal Berkshire Hospital, Reading, Berkshire, UK
- 6Department of Nephrology, Charles University Hospital, Prague, Czech Republic
- 7Department of Nephrology and Internal Medicine, Hospital of Valenciennes, Valenciennes, France
- 8Klinikum Offenbach, Offenbach, Germany
- 9Department of Nephrology, Nuffield Orthopaedic Centre, University of Oxford, Oxford, UK
- 10Primary Systemic Vasculitides Clinic, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico
- 11Norwich Medical School, Norwich and Ipswich Hospital NHS Trust, Ipswich, UK
- 12Department of Medicine, Imperial College London, London, UK
- 13Department of Renal Medicine, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.
- 14Department of Ear, Nose and Throat, Rigshospitalet, Copenhagen, Denmark
- 15University Hospital Gasthuisberg, Leuven, Belgium
- 16Department of Medicine, Addenbrooke's Hospital, Cambridge, UK
- Correspondence to Lorraine Harper, College of Immunity and Infection, University of Birmingham, Birmingham b15 2tt, UK;
Contributors Conception and design were done by K Westman, D Jayne, R Luqmani, L Harper, O Flossmann, C Pusey, C Savage, K de groot and N Rasmussen. All authors contributed to the data collection. Analysis and interpretation of the data were done by P Höglund, K Westman, M Walsh and MD Morgan. Drafting of the article was done by L Harper and MD Morgan. Critical revision of the article for important intellectual content was done by M Walsh, P Hoglund, K Westman, O Flossmann, V Tesar, Phillipe Vanhille7, K de Groot, R Luqmani, LF Flores-Suarez, R Watts, C Pusey, A Bruchfeld, N Rasmussen, D Blockmans C Savage and D Jayne.
- Received 20 July 2011
- Accepted 9 October 2011
- Published Online First 29 November 2011
Introduction The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L et al Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study.
Methods Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised.
Results Median duration of follow-up was 4.3 years (IQR, 2.95–5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs.
Discussion Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial.
Funding The CYCLOPS Trial was supported by the EU (Contract nos. BMH4-CT97-2328 and IC20-CT97-0019. This study was supported by a European League against Rheumatism grant and grants from Region Skåne, Sweden.
Competing interests None.
Ethics approval EUVAS – European Vasculitis Study Group.
Provenance and peer review Not commissioned; externally peer reviewed.