Cross-sectional study assessing long-term safety of interferon-beta-1b for relapsing-remitting MS.
OBJECTIVE
The 16-Year Long-Term Follow-Up (LTF) to the pivotal interferon-beta-1b (IFNbeta-1b) trial explored clinical, MRI, cognitive, and patient-reported outcomes. Here, we report the safety assessments.


METHODS
In the pivotal study, 372 patients were randomized to placebo (n = 123), IFNbeta-1b 50 microg (n = 125), or IFNbeta-1b 250 microg (n = 124) subcutaneously every other day for up to 5 years. Sixteen years later, patients were asked to participate in this cross-sectional follow-up study. No particular therapy was stipulated during follow-up. Adverse events experienced since the pivotal trial were recorded. Neutralizing antibodies (NAbs) to IFNbeta-1b were measured using the myxovirus protein A induction assay. Statistical analyses were descriptive.


RESULTS
In total, 88.2% of patients (328/372) were identified. Some centers achieved 100% ascertainment, obviating selection bias. Treatment-related adverse events (e.g., leukopenia and liver and thyroid dysfunction) reported by LTF participants were in keeping with those previously established. Based on a follow-up period that includes 2,000 patient-years of IFNbeta-1b treatment, no new adverse events were observed that were associated with long-term IFNbeta-1b exposure. By LTF, NAbs to IFNbeta-1b disappeared in the majority (76%) of NAb-positive patients. NAb status during the pivotal study appeared to have no impact on long-term clinical and MRI outcomes. There were more deaths among patients assigned to placebo in the pivotal study (20/109 [18.3%]) compared with patients who received IFNbeta-1b 50 microg (9/108 [8.3%]) or IFNbeta-1b 250 microg (6/111 [5.4%]).


CONCLUSIONS
The results from the 16-Year Long-Term Follow-Up study support the long-term safety of interferon-beta-1b therapy in multiple sclerosis.


METHODS
This study provides Class III evidence that patients with relapsing-remitting MS taking IFNbeta-1b 50 microg or 250 microg subcutaneously every other day for up to 5 years, with subsequent unspecified treatment, have fewer deaths after 16 years of follow-up than similar patients on placebo for up to 5 years, with subsequent unspecified treatment (risk difference 11.5%, 95% confidence interval 4-19).
Reder
A T
AT
Department of Neurology, University of Chicago, Chicago, IL 60637, USA. areder@neurology.bsd.uchicago.edu
Ebers
G C
GC
Traboulsee
A
A
Li
D
D
Langdon
D
D
Goodin
D S
DS
Bogumil
T
T
Beckmann
K
K
Konieczny
A
A
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000906:Antibodies / Q000097:blood; D003430:Cross-Sectional Studies; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D017063:Outcome Assessment, Health Care; D016019:Survival Analysis; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000068576:Interferon beta-1b; D016899:Interferon-beta