Final results from the interferon beta-1b 16-year long-term follow-up study

G. Ebers, A. Traboulsee, D. Li, D. Langdon, D.S. Goodin, A. Reder, A. Konieczny for the Betaseron/Betaferon LTF Study Group

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Background: The pivotal interferon beta-1b (IFNB-1b; Betaferon®) study demonstrated efficacy, safety and tolerability of IFNB-1b in patients with relapsing forms of multiple sclerosis (MS) and led to the first approved immunomodulatory therapy for MS.

The 16-Year Long-Term Follow-up (LTF) study is primarily hypothesis generating, and aims to evaluate the long-term treatment effects of IFNB-1b on clinical and imaging parameters, cognitive function and patient-reported outcomes.

Design/Methods: The LTF is a multicentre, open-label, observational study that evaluates outcomes in patients having participated in the original IFN-1b pivotal trial which began in 1988. Survival, disease status, relapse rate, Expanded Disability Status Scale (EDSS) score, adverse events, magnetic resonance imaging parameters and other data have been collected.

Results to date have been divided and analysed by the original treatment assignment in the pivotal trial (placebo, 50 mcg IFNB-1b subcutaneously [sc] or 250 mcg IFNB-1b sc every other day, and arbitrarily in advance by the duration of treatment.

Over the 16 years results were divided into “never” = IFNB-1b <=10% of the time; “ever” = IFNB-1b >10–80% of the time; “always” = IFNB-1b >80% of the time.

Results: Of the original 372 patients, 328 have been identified (i.e. 88.2%); 293 of these patients are alive and 35 are deceased. Median time from diagnosis was 19 years. Data from 260 patients indicate that 78/260 (30%) patients are currently taking IFNB-1b, and the median length of exposure to IFNB-1b has been almost 10 years (3345 days). Wheelchair use is required by 44.2% of “never” patients and 29.4% of “always” patients. Median time to EDSS 6 was 6 years later for “always” patients than for “never” patients. Annualised relapse rates were lower in the “always” group, compared with the “never” group. Adverse events were uncommon. More detailed analyses are ongoing.

Conclusions: This is the longest and most complete follow-up of any disease modifying drug for MS. After 16 years, 88.2% of patients from the pivotal IFNB-1b trial have been located. Long-term safety of IFNB-1b is excellent. Results are consistent with the hypothesis that continuous long-term treatment positively impacts on the disease course but selection bias cannot be excluded. Comparisons are being made to natural history data from the Ontario cohort. The lack of randomisation and blinding in observational studies may be offset by the clarity of their outcomes.