Format

Send to

Choose Destination
PLoS One. 2017 Jan 3;12(1):e0168834. doi: 10.1371/journal.pone.0168834. eCollection 2017.

Double-Blind Controlled Randomized Trial of Cyclophosphamide versus Methylprednisolone in Secondary Progressive Multiple Sclerosis.

Author information

1
Service de Neurologie et INSERM-CHU CIC-P 0005, CHU de Bordeaux, Bordeaux, France.
2
INSERM U 1215, Université de Bordeaux, Bordeaux, France.
3
Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique, Pôle de Santé Publique, CHU de Bordeaux, Bordeaux France.
4
Service de Neurologie, CHU de Nancy, Nancy, France.
5
Service de Neurologie, CHU de Clermont-Ferrand, Clermont-Ferrand, France.
6
Service de Neurologie et CIC INSERM 1434, CHU de Strasbourg, Strasbourg, France.
7
Univ. Lille, CHU Lille, LIRIC-INSERM U995, FHU Imminent, Lille, France.
8
Service de Neurologie, CHU de Nîmes, Nîmes, France.
9
Service de Neurologie, CHU de Montpellier, Montpellier, France.
10
Service de Neurologie, CHU de Nice, Nice, France.

Abstract

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 /m2 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.

PMID:
28045953
PMCID:
PMC5207788
DOI:
10.1371/journal.pone.0168834
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist for this work. Dr. Brochet reports grants from French Ministry of Health, during the conduct of the study; personal fees and non-financial support from Biogen, Genzyme, Roche, Bayer, Teva and Novartis; research grants from merck-serono and Teva, outside the submitted work. Dr. Debouverie reports personal fees and non-financial support from Biogen-idec, Novartis, Merck-Serono and Genzyme, outside the submitted work. Dr. Vermersch reports grants, personal fees and non-financial support from Biogen, Roche, Merck-Serono, Novartis; personal fees from Almirall and Bayer; personal fees and non-financial support from Genzyme-Sanofi, and Teva; grants and personal fees from Bayer, outside the submitted work. Dr. Perez reports grants from Health Ministry, during the conduct of the study. Dr. Cohen reports personal fees from Biogen Idec, Bayer Schering Pharma, Merck Serono, Teva, Genzyme-Sanofi and Novartis, outside the submitted work. Dr. Ouallet reports grants, personal fees and non-financial support from Biogen, Merck-Serono, Novartis and Teva; personal fees and non-financial support from Genzyme; personal fees from Roche; grants, grants and non-financial support from sigma-tau, outside the submitted work. Dr. Ruet reports personal fees and other from Biogen-idec; grants from Teva; personal fees and other from Novartis; other from Genzyme; other from Roche; other from Merck-Serono; non-financial support from Bayer, outside the submitted work. Dr. Zéphir reports grants from ARSEP; grants and non-financial support from Teva, Biogen, Bayer, Novartis, Sanofi and Genzyme; non-financial support from Merck, outside the submitted work. Drs. Labauge, Collongues, de Sèze, Lebrun, Castelnovo, and Pittion, Ms. Deloire, Baschet, and Mt Loock have nothing to disclose. This does not alter our adherence to all PLOS ONE policies on sharing data and materials.

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center