Free Communications 3Friday, October 04, 2013, 10:03 - 10:15
Double-blind, randomized, controlled study of cyclophosphamide versus methylprednisolone in secondary progressive multiple sclerosis: PROMESS studyB. Brochet, M. Deloire, P. Perez, T. Loock, L. Baschet, J.C Ouallet, A. Ruet for PROMESS study group
Background: Therapeutic strategies are very limited in secondary progressive MS (SPMS). Cyclophosphamide (CPM) has shown encouraging results in open studies but has not been rigorously evaluated.
Objectives: To study the efficacy of intravenous (IV) CPM as compared to IV methyprednisolone (MP) every 4 weeks during 1 year and every 8 weeks during a second year on evolution of physical disability in SPMS patients.
Methods: Multicentre, randomized, double-blind, controlled phase III clinical trial, with two parallel arms comparing: CPM to MP. The patients received every 4 weeks during 1 year and every 8 weeks during 1 year a dose of 750mg / m˛ body surface area of IV CPM or 1 g of IVMP. Inclusion criteria were SPMS patients, aged 18-65 years, EDSS between 4.0 and 6.5 inclusive, progressive deterioration phase > 6 month and < 3 years and with a documented reduction of walking distance in the last 12 months. The clinical assessment was done every 4 weeks during 1 year and every 8 weeks the second year by experienced trained neurologist blinded for treatment assignation. The primary outcome was the delay to confirmed EDSS deterioration. The secondary outcomes were walking distance, proportion of patients with EDSS deterioration, relapse rate, MSFC and safety. Intent to-treat analysis was carried out. The primary endpoint was analyzed using the Kaplan-Meier method and the delay of EDSS deterioration was compared between treatment groups by log-rank test.
Results: 138 SPMS patients were randomised and allocated in the two groups. The blinded analysis showed that the mean duration of treatment was 94 weeks (range 34 -101 weeks). Fifty-two patients stopped treatment prematurely, and it was for adverse events in 24 cases. 28 serious adverse events were reported. The unblinding of the data base will be done in June 2013.
Conclusion: Final results will be presented at the ECTRIMS congress.
Acknowledgements: This study was promoted by CHU de Bordeaux and supported par Programme Hospitalier de Recherche Clinique 2004.
B. Brochet or his institution has received honoraria for speaking at scientific meetings and serving as a member of scientific advisory boards for Bayer Pharma, Biogen-Idec, Merck Serono, Genzyme, Novartis, and Teva, and his institution has received research grants from Bayer Pharma, Teva, Merck Serono, Novartis, Biogen-Idec, Sanofi-Aventis and Roche.
A. Ruet participated as a speaker for symposia organized by Biogen-Idec and Teva. She is or was an investigator for studies promoted by Novartis,Bayer Healthcare, Roche, Lilly, Peptimmune, and Merck-Serono and has received subventions for this activity. She received research support from Novartis. She is also a recipient of a fellowship-grant from Fondation pour la Recherche Médicale.
Dr JC Ouallet has received consultancy fees, speaker fees, research grants (non-personal), and honoraria from Novartis, Biogen-Idec, Merck-Serono, and Sanofi-Aventis.
M. Deloire, T. Loock, P. Perez and L Bachet report no disclosure.