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Association Between Immediate Initiation of Intramuscular Interferon Beta-1a at the Time of a Clinically Isolated Syndrome and Long-term Outcomes:  A 10-Year Follow-up of the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurological Surveillance

R. Philip Kinkel, MD; Mariya Dontchev, MPH; Craig Kollman, PhD; Thomai T. Skaramagas, BA; Paul W. O’Connor, MD; Jack H. Simon, MD, PhD; for the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurological Surveillance Investigators
Arch Neurol. 2012;69(2):183-190. doi:10.1001/archneurol.2011.1426.
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Objective To determine whether immediate initiation of treatment at the time of a clinically isolated syndrome in patients at high risk for clinically definite multiple sclerosis alters disease course over 10 years.

Design Prospective follow-up study.

Setting Twenty-four Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) sites in the United States and Canada.

Participants A total of 81 patients originally randomly assigned to receive intramuscular interferon beta-1a (the immediate-treatment group) and 74 patients originally randomly assigned to receive placebo (the delayed-treatment group). All patients were from CHAMPS.

Intervention For the immediate-treatment group, treatment was initiated within a month after the onset of a clinically isolated syndrome, and for the delayed-treatment group, treatment was initiated a median of 30 months (interquartile range, 24-35 months) after CHAMPS randomization.

Main Outcome Measures Rate of developing clinically definite multiple sclerosis, annualized relapse rate, disease course classification, disability measures, and magnetic resonance imaging measures.

Results The immediate-treatment group showed a lower 10-year rate of clinically definite multiple sclerosis (unadjusted hazard ratio, 0.64 [95% CI, 0.48-0.87]; P = .004) and a lower annualized relapse rate between years 5 and 10 (P = .03). There was no differential effect on disability, magnetic resonance imaging T2-weighted lesions, or the proportion of patients developing progressive disease at 10 years. Few patients reached the Expanded Disability Status Scale milestone scores of 4.0 or greater (9% of patients) or 6.0 or greater (6% of patients).

Conclusions Immediate initiation of intramuscular interferon beta-1a at the time of a clinically isolated syndrome in high-risk patients reduces relapse rates over 10 years but does not improve disability outcomes compared with a control group that also initiated therapy relatively early in the disease course.

Trial Registration clinicaltrials.gov Identifier: NCT00179478

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Figures

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Figure 1. Progression from the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) through the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurological Surveillance (CHAMPIONS). Thirty-two of the 50 CHAMPS sites participated in the CHAMPIONS 5-year follow-up (a total of 293 CHAMPS patients at these 32 sites). Twenty-four of the 32 CHAMPIONS 5-year follow-up sites participated in the CHAMPIONS 10-year extension (a total of 183 CHAMPS patients at these 24 sites). The percentages in the bottom row of boxes are based on the participants enrolled in the 10-year extension. The percentage among all CHAMPS participants who completed the 10-year evaluation was 35% in the immediate-treatment group and 31% in the delayed-treatment group. The median follow-up time for all subjects participating in the 10-year extension was 10.0 years.

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Figure 2. Kaplan-Meier rates for the development of clinically definite multiple sclerosis (CDMS) by treatment group, calculated using timing from the first month. Data include all patients (n = 383) originally randomly assigned to the Controlled High-Risk Subjects Avonex Multiple Sclerosis Prevention Study. Patients not meeting the criteria for CDMS were censored on the date of their last neurologic examination.

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