Treatment of the Earliest Signs of Multiple Sclerosis Shows Benefits

Several clinical outcomes favored earlier treatment after patients have had a first episode suggestive of multiple sclerosis (MS), known as clinically isolated syndrome (CIS), compared with a short delay in treatment, according to a new study.

Although the average delay in treatment initiation was only 1.5 years, the researchers saw benefits of early treatment 11 years later.

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“The most astonishing observation was that relapse rates remained lower in most of the years after both groups had equal access to treatment,” said lead study author Ludwig Kappos, MD, of University Hospital Basel in Basel, Switzerland. “This finding suggests the possibility of a more remote effect of early intervention on the pathogenic factors that contribute to detectable attacks.”

The researchers randomly assigned participants in the BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment) study to receive interferon beta-1b (early treatment) or placebo (delayed treatment). After conversion to clinically definite multiple sclerosis (CDMS) or 2 years, patients on placebo could switch to interferon beta-1b or another treatment.

Eleven years after randomization, the investigators reassessed 278 (59.4%) of the original 468 patients (167 [57.2%] in the early-treatment group and 111 [63.1%] in the delayed-treatment group). They found that risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm, with longer time to first relapse (median, 1888 days vs 931 days) and a lower overall annualized relapse rate (0.21 vs 0.26). Only 25 patients (5.9%, overall; 4.5% in the early-treatment group, and 8.3% in the delayed-treatment group) converted to secondary progressive MS.

Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms. The early-treatment group had better cognitive function as quantified by Paced Auditory Serial Addition Task-3 test total scores. Employment rates remained high, and health resource utilization tended to be low in both groups. Results of magnetic resonance imaging scans did not differ between the groups.

“It makes sense to offer early treatment to patients with first symptoms highly suggestive of MS if other diagnoses are thoroughly excluded by a competent neurologist and treatment is well tolerated at the short and long term,” Dr Kappos said. “It is reassuring to people with MS and physicians to see that little progression occurred in both treatment groups over these 11 years. For me, this underlines that although the options are better with a very early intervention, the window of opportunity remains open for some time.”

The researchers plan to conduct a 15-year follow-up study and explore prognostic factors for long-term outcomes in this patient cohort.

—Mike Bederka

Kappos L, Edan G, Freedman MS, et al; BENEFIT Study Group. The 11-year long-term follow-up study from the randomized BENEFIT CIS trial [published online August 10, 2016]. Neurology. doi:10.1212/WNL.0000000000003078.