Effectiveness of glatiramer acetate in neutralizing antibody-positive patients previously treated with interferon-β

BACKGROUND: Some patients with multiple sclerosis who are treated with interferon-β(IFNβ) develop neutralizing antibodies (NAbs), which reduce or abolish the therapeutic effects of the treatment. These patients are usually switched to a non-IFNβ treatment, such as glatiramer acetate (GA). It is unknown whether a patient's previous disease activity in combination with their NAb-status can provide further insights on their risk of future disease activity. Consequently, we investigated treatment outcomes in patients switching from IFNβ to GA according to NAb-status and clinical disease activity, while on IFNβ.

METHODS: We identified all patients switching from IFNβ to GA and having information on NAb-status from the Danish Multiple Sclerosis Registry and compared treatment outcomes while on GA according to previous disease activity and the presence of NAbs.

RESULTS: We included 568 patients in the study: 107 NAb-negative patients switched due to adverse events (group 1), 24 NAb-negative patients switched with disease activity (group 2), 397 NAb-positive patients switched without disease activity (group 3) and 40 NAb-positive patients switched with disease activity (group 4). Compared to the reference (group 1), group 2 had an increased risk of future relapses (HR 1.79 95% Confidence interval (CI): 1.00-3.19). Group 3 showed a trend of a lower risk of future relapses (HR 0.74, 95%CI: 0.53-1.04). Group 4 had, on average, a similar risk of future relapses (HR 1.15 95% CI: 0.69-1.92). Similarly, group 2 had a higher probability of treatment discontinuation due to disease activity compared to the other groups.

CONCLUSION: While on GA, patients switched from IFNβ in the context of disease activity and no NAbs had the highest risk of future disease activity, while NAb positive patients without previous activity had the lowest. We did not find any average difference between NAb-positive patients switching in a context of disease activity and NAb-negative patients switched due to adverse events, although carefulness in the interpretation of this result is advised.