The clinical effect of neutralizing antibodies against interferon-beta is independent of the type of interferon-beta used for patients with relapsing-remitting multiple sclerosis
Objective To establish whether the clinical effect of neutralizing antibodies (NAbs) against interferon-beta (IFNβ) depends on the type of IFNβ (1a or 1b) used for treatment of patients with relapsing-remitting multiple sclerosis (MS). Introduction NAbs against IFNβ-1b appear faster and may be more evenly distributed on IgG subclasses, whereas NAbs against IFNβ-1a develop more slowly and may be devoid of IgG3. This might cause different clinical responses to NAbs. Design/patients All Danish MS-patients who had started first-time treatment with IFNβ-1a 22 μg s.c tiw (Rebif22) or IFNβ-1b 250 μg s.c. qod (Betaferon) before January 1st 2003 were included. Relapses were recorded at bi-annual visit. Methods We measured NAbs every 12 months using a clinically validated cytopathic effect assay. A blood sample with a neutralizing capacity of 20% or more was considered as NAb-positive. We used a mixed logistic regression analysis in which NAb-status (three levels), IFNβ-preparation, and time since treatment started were included as explanatory variables, and relapse rate as response variable. Results In 1,309 patients, who were observed for 21,958 months, 32.3% were classified as NAb-positive. The odds-ratio (OR) for relapses in NAb-positive months compared with NAb-negative months was 1.25; P = 0.02. The risk of relapses was higher with Betaferon than with Rebif22 (OR 1.26; P < 0.01). The effect of NAb-level on relapses was independent of whether the patients were treated with Betaferon or Rebif22 ( P = 0.89) and of time ( P = 0.80). Conclusion NAbs caused by IFNβ-1a s.c. do not differ from NAbs caused by IFNβ-1b in their detrimental clinical effect.