AMSTERDAM – MRI of the brain performed 1 year after starting disease-modifying treatment for relapsing-remitting multiple sclerosis predicted response to treatment at 5 years in a retrospective, observational, single-center study.
Several other baseline predictors of a better response to disease-modifying treatment (DMT) at 5 years included male sex, a low EDSS (Expanded Disability Status Scale) score, the presence of monofocal disease, and fewer gadolinium-enhancing (GdE) T1-weighted lesions on MRI.
Previous studies have found that MRI performed 1 year after initiation of DMT can predict treatment response in the subsequent 2-3 years (Eur. J. Neurol. 2009;16:1202-9; Mult. Scler. 2009;15:848-53). But Dr. Marzia Romeo, the lead investigator of the current study, and her colleagues sought to determine if it could also predict longer-term outcomes.
"One of our many issues is to identify patients who benefit from first-line therapy for MS," said Dr. Romeo of the San Raffaele Hospital in Milan at the joint triennial congressof the European and Americas Committees for Treatment and Research in Multiple Sclerosis (ECTRIMS/ACTRIMS).
The investigators selected 668 patients with relapsing-remitting multiple sclerosis (RRMS) who started treatment with a first-line DMT (interferon beta-1a or glatiramer acetate [Copaxone]) in 1996-2005 and had at least 5 years of follow-up data available. Of the 668 patients who were eligible, 398 (60%) had undergone MRI after 1 year of therapy.
The mean ages for MS onset and the start of first-line DMT were 28.9 years and 34.5 years, respectively. The majority of patients in the cohort (77%) were women.
"One of our many issues is to identify patients who benefit from first-line therapy for MS."
After 5 years of treatment, Dr. Romeo and her associates classified 33% of patients as full responders, 22% as partial responders, and the remaining 45% as nonresponders. They defined treatment response according to the following clinical criteria:
• Full response. The patient had no sign of clinical relapse, and there was less than a 1.5-point increase in the EDSS score.
• Partial response. The patient experienced one or more relapses but had an EDSS score increase of 1.5 points or less.
• Nonresponse. The EDSS score increased by 1.5 points or more starting at 6 months after initiation of DMT, and persisted up to the 5-year follow-up examination, or the use of a second-line therapy.
Slightly more than half (51%) of the study population were treated with the same DMT throughout the 5-year evaluation period. Another 37% switched to an alternative DMT, and 12% switched to a second-line therapy.
Dr. Romeo reported that 78% of full responders remained on the same DMT that they started at the beginning of treatment, compared with only 17% of nonresponders.
The presence of more than two GdE T1 lesions at 1 year was associated with nearly sixfold greater odds for nonresponse to DMT at 5 years in a comparison of full- and nonresponders (P less than .0001).
At baseline, full responders were significantly more likely than nonresponders to be male (75% vs. 65%) and to have a lower EDSS score (mean, 1.6 vs. 2.1), a lower prevalence of multifocal disease (21% vs. 30%), and a lower prevalence of two or more GdE T1 lesions (18% vs. 32%). Dr. Romeo noted that patients with these characteristics at baseline should be considered for induction therapy.
"In the subgroup of patients in whom we performed MRI after 1 year of treatment, we observed that the patients with more than two active lesions were nonresponders and had a high risk of disability progression after the 5 years’ follow-up," she said. An alternative treatment should be considered in these patients with active lesions (defined as a new T2 or GdE T1 lesions, "before irreversible neurological disability occurs."
Dr. Romero reported having no conflicts of interest. Several of her coauthors disclosed receiving research grants or receiving honoraria for speaking, consulting, or participating on an advisory board for Actelion, Bayer Schering Pharma, Biogen-Dompé SG (and Biogen Idec), Merck Serono, Novartis, Sanofi-Aventis, Serono Symposia International Foundation, Synthon, and Teva Pharmaceuticals.