Statistical approaches to assessing the effects of neutralizing antibodies: IFNbeta-1b in the pivotal trial of relapsing-remitting multiple sclerosis.

Carefully conducted large-scale clinical trials have provided strong evidence that type I interferons favorably influence clinical and MRI outcomes in patients with multiple sclerosis. Some patients develop neutralizing antibodies (NAbs) to these treatments, reflecting an immune system response. The clinical significance of these NAbs has been uncertain because titers vary widely, and even highly elevated NAb titers decrease to undetectable levels in some patients. Whether NAbs decrease the efficacy of these treatments is a critically important scientific question. We argue that a longitudinal data analysis is the most appropriate approach to address this question.