The 11-year long-term follow-up study from the randomized BENEFIT CIS trial.

Kappos, Ludwig; Edan, Gilles; Freedman, Mark S; Montalbán, Xavier; Hartung, Hans-Peter; Hemmer, Bernhard; Fox, Edward J; Barkhof, Frederik; Schippling, Sven; Schulze, Andrea; Pleimes, Dirk; Pohl, Christoph; Sandbrink, Rupert; Suarez, Gustavo; Wicklein, Eva-Maria; Mattle, Heinrich (2016). The 11-year long-term follow-up study from the randomized BENEFIT CIS trial. Neurology, 87(10), pp. 978-987. American Academy of Neurology 10.1212/WNL.0000000000003078

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OBJECTIVE To assess outcomes for patients treated with interferon beta-1b immediately after clinically isolated syndrome (CIS) or after a short delay. METHODS Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for Initial Treatment) were randomly assigned 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, patients were reassessed. RESULTS Two hundred seventy-eight (59.4%) of the original 468 patients (71.3% of those eligible at participating sites) were enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk of CDMS remained lower in the early-treatment arm compared with the delayed-treatment arm (p = 0.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888 [540, not reached] vs 931 [253, 3,296]; p = 0.0005) and lower overall annualized relapse rate (0.21 vs 0.26; p = 0.0018). Only 25 patients (5.9%, overall; early, 4.5%; delayed, 8.3%) converted to secondary progressive multiple sclerosis. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms (median [Q1, Q3]: 2.0 [1.0, 3.0]). The early-treatment group had better Paced Auditory Serial Addition Task-3 total scores (p = 0.0070). Employment rates remained high, and health resource utilization tended to be low in both groups. MRI metrics did not differ between groups. CONCLUSIONS Although the delay in treatment was relatively short, several clinical outcomes favored earlier treatment. Along with low rates of disability and disease progression in both groups, this supports the value of treatment at CIS. CLINICALTRIALSGOV IDENTIFIER NCT01795872. CLASSIFICATION OF EVIDENCE This study provides Class IV evidence that early compared to delayed treatment prolongs time to CDMS in CIS after 11 years.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Sahli Building > Forschungsgruppe Neurologie
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Mattle, Heinrich


600 Technology > 610 Medicine & health




American Academy of Neurology




Stefanie Hetzenecker

Date Deposited:

23 Mar 2017 16:10

Last Modified:

22 Jan 2019 10:58

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