KLINICKÉ ZKOUŠKY REBIFU PŘED REGISTRACÍ


Subcutaneous interferon β1a (Rebif, EMD Serono, Inc.)

The Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis (PRISMS) trial was a 2-year randomized, double-blind, placebo-controlled, multi-centered trial of 560 patients with RRMS. Subjects treated with either the 22 or 44 μg dose of IFN-β1a subcutaneously showed a significant reduction in ARRs compared with placebo, 27% and 33% respectively. Both treatment groups showed a significant reduction in the number of new or enlarging T2 lesions; 67% reduction in the 22 μg group and 78% reduction in the 44 μg group [PRISMS Study Group, 1998]. An extension study utilizing a crossover design in which placebo-treated patients were randomized to either 22 or 44 μg of IFN-β1a subcutaneously after 2 years revealed patients in both active treatment groups for the entire 4 years continued to show significantly lower number of relapses per year [PRISMS Study Group, 2001]. IFNs have immunogenic properties and treated individuals may develop binding and neutralizing antibodies (NAbs) to these products. NAbs may develop with the use of all formulations of IFN-β; however, they are found more commonly with the high-dose, high-frequency IFNs (IFN-β1b and IFN-β1a subcutaneously). The issue of NAbs is controversial; however, a panel of experts met at the Neutralizing Antibodies on Interferon Beta in Multiple Sclerosis (NABINMS) consortium in 2009 in attempts to formulate a practical approach to the evaluation and incorporation of information regarding NAbs in the treatment of MS. The group proposed that both the NAb titer and clinical status of the patient should be considered in the decision regarding the impact of the presence of NAbs on changing DMTs. They also suggested reevaluation of the NAbs status prior to making a change in therapy unless patients were clearly performing poorly clinically [Polman et al. 2010].