Key result
Interferon beta-1a 60 microg resulted in a higher incidence of neutralizing antibodies compared to 30 microg (4.8% vs 1.8%; p=0.02), which was associated with higher relapse rates and MRI activity.
Why the study?
Does the dose of interferon beta-1a affect the incidence of neutralizing antibodies, and do these antibodies reduce therapeutic efficacy in patients with relapsing multiple sclerosis?
RCT (n=795)
randomized
Yes
Does the dose of interferon beta-1a affect the incidence of neutralizing antibodies, and do these antibodies reduce therapeutic efficacy in patients with relapsing multiple sclerosis?
Absolute Event Rate: 4.8% vs 1.8%
p-value: p=0.02
Neutralizing antibodies to interferon beta-1a reduce its therapeutic benefits in relapsing multiple sclerosis, with higher doses associated with a higher incidence of antibody formation.
Prefer 30-μg interferon beta-1a to limit neutralizing antibodies; confirms their association with reduced efficacy in relapsing MS.
OBJECTIVE: To determine the incidence and clinical significance of neutralizing antibody (NAb) formation in patients with relapsing multiple sclerosis (MS) who participated in the European Interferon Beta-1a IM Dose-Comparison Study. METHODS: Patients were randomized to treatment with interferon beta-1a (IFNbeta-1a) 30 microg or 60 microg IM once weekly for up to 4 years. Serum samples obtained at baseline and every 3 months thereafter were screened for the presence of IFN binding antibodies by ELISA. Patients whose results were seropositive on ELISA were screened for the presence of NAbs using an antiviral cytopathic effect assay. Patients were considered to be positive for NAbs (NAb+) if the baseline NAb titer was 0 and two or more consecutive postbaseline titers were > or = 20. Patients were considered to be negative for NAbs (NAb-) if the baseline NAb titer was 0 and all postbaseline NAb titers were < 5. RESULTS: The proportion of patients who became NAb+ was lower in patients who received 30 microg of IFNbeta-1a than in those who received 60 microg (7/400 [1.8%] vs 19/395 [4.8%]; p = 0.02). The mean time to NAb+ status was 14.5 +/- 6.2 months. Compared with patients who remained NAb-, NAb+ patients showed the following: higher relapse rates from months 12 to 48 (p = 0.04), higher rate of mean change (worsening) in Expanded Disability Status Scale score from baseline to month 48 (p = 0.01), greater number of T1 gadolinium-enhanced lesions at months 24 and 36 (p = 0.02 and 0.03), and greater accrual of new or enlarging T2 lesions from month 12 to months 24 and 36 (p = 0.05 and 0.09). CONCLUSIONS: Neutralizing antibodies (NAbs) to interferon beta-1a (IFNbeta-1a), as observed with other IFNbetas used in the treatment of multiple sclerosis, reduce the therapeutic benefits measured by relapses and MRI activity. Data from this study also suggest NAbs to IFNbeta-1a reduce treatment benefits as measured by change in Expanded Disability Status Scale score.
No takes yet. Share an insight, caveat, or question.
Kappos et al. (2005) conducted an RCT in Relapsing multiple sclerosis (n=795). Interferon beta-1a vs. Interferon beta-1a 30 microg IM once weekly was evaluated on Proportion of patients who became positive for neutralizing antibodies (NAb+) (p=0.02). Interferon beta-1a 60 microg resulted in a higher incidence of neutralizing antibodies compared to 30 microg (4.8% vs 1.8%; p=0.02), which was associated with higher relapse rates and MRI activity.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: