Open AccessDouble-Blind Controlled Randomized Trial of Cyclophosphamide versus Methylprednisolone in Secondary Progressive Multiple Sclerosis
Author(s) -
Bruno Brochet,
Mathilde Deloire,
Paul Perez,
Timothé Loock,
Baschet Louise,
Marc Debouverie,
Sophie Pittion,
J.-C. Ouallet,
Pierre Clavelou,
Jérôme De Sèze,
Nicolas Collongues,
Patrick Vermersch,
Hélène Zephir,
Giovanni Castelnovo,
Pierre Labauge,
C. Lebrun,
Mikaël Cohen,
Aurélie Ruet,
Promess study investigators
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0168834
Subject(s) - medicine , expanded disability status scale , clinical endpoint , multiple sclerosis , tolerability , methylprednisolone , randomized controlled trial , hazard ratio , cyclophosphamide , clinical trial , adverse effect , surgery , chemotherapy , confidence interval , psychiatry
Background Therapeutic options are limited in secondary progressive multiple sclerosis (SPMS). Open-label studies suggested efficacy of monthly IV cyclophosphamide (CPM) without induction for delaying progression but no randomized trial was conducted so far. Objective To compare CPM to methylprednisolone (MP) in SPMS. Methods Randomized, double-blind clinical trial on two parallel groups. Patient with SPMS, with a documented worsening of the Expanded Disability Status Scale (EDSS) score during the last year and an EDSS score between 4·0 and 6·5 were recruited and received one intravenous infusion of treatment (CPM: 750 mg /m 2 body surface area—MP: 1g) every four weeks for one year, and every eight weeks for the second year. The primary endpoint was the time to EDSS deterioration, when confirmed sixteen weeks later, analyzed using a Cox model. Results Due to recruitment difficulties, the study was terminated prematurely after 138 patients were included (CPM, n = 72; MP, n = 66). In the CPM group, 33 patients stopped treatment prematurely, mainly due to tolerability, compared with 22 in the MP group. Primary endpoint: the hazard ratio for EDSS deterioration in the CPM in comparison with the MP group was 0.61 [95% CI: 0·31–1·22](p = 0·16). According to the secondary multistate model analysis, patients in the CPM group were 2.2 times more likely ([1·14–4.29]; p = 0.02) to discontinue treatment than those in the MP group and 2.7 times less likely (HR = 0.37, 95% CI: 0.17–0.84; p = 0.02) to experience disability progression when they did not stop treatment prematurely. Safety profile was as expected. Conclusion Although the primary end-point was negative, secondary analysis suggested that CPM decreases the risk of progression in SPMS, but its use may be limited by low tolerability. Trial Registration Clinicaltrials.gov NCT00241254