Abstract
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.
ClinicalTrials.gov 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.
GLOSSARY
- ARR=
- annualized relapse rate;
- BENEFIT=
- Betaferon/Betaseron in Newly Emerging MS for Initial Treatment;
- CDMS=
- clinically definite multiple sclerosis;
- CI=
- confidence interval;
- CIS=
- clinically isolated syndrome;
- DMT=
- disease-modifying therapy;
- EDSS=
- Expanded Disability Status Scale;
- EQ-5D=
- EuroQoL–5 Dimension;
- FAMS=
- Functional Assessment of Multiple Sclerosis;
- Gd+=
- gadolinium-enhancing;
- KM=
- Kaplan-Meier;
- MS=
- multiple sclerosis;
- PASAT=
- Paced Auditory Serial Addition Task;
- Q=
- quartile;
- RR=
- risk ratio;
- SDMT=
- Symbol Digit Modalities Test;
- SPMS=
- secondary progressive multiple sclerosis
Footnotes
↵† Deceased.
BENEFIT Study Group coinvestigators are listed at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by Bayer Pharma AG/Bayer HealthCare Pharmaceuticals.
Supplemental data at Neurology.org
Editorial, page 970
- Received September 28, 2015.
- Accepted in final form April 14, 2016.
- © 2016 American Academy of Neurology
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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