Patients with secondary progressive multiple sclerosis who were able to stay on cyclophosphamide therapy had a lower risk of further disability, but their dropout rate from treatment was more than twice that for methylprednisolone therapy, researchers reported here.
Of the 72 patients enrolled in the cyclophosphamide arm of the trial, 33 dropped out of treatment before the end of the 2-year study -- 20 of them due to adverse events, reported Bruno Brochet, MD, chief of neurology at the University of Bordeaux Segalen, France.
Even though risk of decline of the Expanded Disability Status Scale score was reduced 58% by treatment with cyclophosphamide, in the intention-to-treat analysis the use of cyclophosphamide failed to reach statistical significance as a superior treatment to methylprednisolone, a standard of care in France, Brochet said in his oral presentation at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.
In the primary endpoint analysis, 18.1% of patients treated with cyclophosphamide experienced definite deterioration as measured by the Expanded Disability Status Scale score, compared with 31.8% of the patients taking methylprednisolone (P=0.06), he said.
He illustrated that treatment with cyclophosphamide decreased the risk of deterioration by 58% (95% CI 0.19-0.92), but the hazard ratio of premature end of treatment was 2.56 (95% CI 1.13-5.79).
Among secondary endpoints, Brochet said there were no significant differences in timed walking distances, or in the Multiple Sclerosis Functional Composite, between the two groups.
He said that 76.6% of those on cyclophosphamide were relapse-free after 2 years compared with 56.1% of those on prednisolone, but that again missed statistical significance (P=0.07).
"According to the multi-state model, cyclophosphamide is a risk factor for treatment interruption, but cyclophosphamide is protecting patients who continued their treatment from progression as assessed by the Expanded Disability Status Scale," Brochet said.
"I do not think these results are compelling for use of cyclophosphamide," said Vesna Brinar, MD, professor of neurology at University of Zagreb, Croatia, who moderated the free communications session at ECTRIMS.
"The high dropout rate indicates that this treatment might be useful only in carefully selected patients," she told MedPage Today.
In the study, Brochet and colleagues randomly assigned 72 individuals with secondary progressive multiple sclerosis to cyclophosphamide and 66 similar patients to treatment with methylprednisolone. Brochet, in responding to questions from his audience, said the researchers did not include a placebo group because of the widespread use in France of methylprednisolone as a standard of care in the disease.
"Therapeutic options are very limited in secondary progressive multiple sclerosis," he noted.
He said the researchers in the so-called PROMESS study considered the use of cyclophosphamide as an agent that could reduce inflammation, an ongoing process that is believed to have a role in secondary progressive multiple sclerosis.
Patients at 27 participating centers in France were randomly assigned to either cyclophosphamide or methylprednisolone and were administered intravenous therapy monthly for 1 year, and then every other month for the second year of the trial. Patients were admitted to the trial if they exhibited a phase of gradual progression of disability of at least 6 months, but less than 4 years. The recent deterioration must have been at least a 0.5 worsening score on the Expanded Disability Status Scale score over the past 12 months.
The patients were about 48 years of age; about 65% were women; their average disease duration was around 12 years. Their median Expanded Disability Status Scale score was 5 (eligible patients had to score between 4 and 6.5 on the scale.)
Patients on cyclophosphamide averaged 8.6 adverse events compared with 6.2 adverse events on prednisolone. He said that 70 of 72 patients on cyclophosphamide had at least one adverse event, compared with 61 of 66 patients on prednisolone.
This study was promoted by CHU de Bordeaux and supported by the Programme Hospitalier de Recherche Clinique 2004.
Brochet disclosed commercial relationships with Bayer Pharma, Biogen-Idec, Merck Serono, Genzyme, Novartis, sanofi, Roche and Teva. Co-authors also disclosed commercial relationships with Almirall, Bayer-Schering, Lilly, and Peptimmune.
Brinar had no disclosures.
Primary source: European Committee for Treatment and Research in Multiple Sclerosis
Source reference: Brochet B, et al "Double-blind, randomized, controlled study of cyclophosphamide versus methylprednisolone in secondary progressive multiple sclerosis: PROMESS study" ECTRIMS 2013; Abstract 169.
Source: MedPage Today © 2013 MedPage Today, LLC (07/10/13)