The goal of the CombiRx study was to determine whether glatiramer acetate combined with interferon beta-1a was better than either drug alone. The study used “double-dummy” injections to blind participants to the study arm. Consequently, each patient was required to take eight injections per week for a minimum of three years. Including this feature was difficult but important in minimizing bias. The investigators and participants should be congratulated for completing a challenging study in an exemplary fashion.
The combination resulted in less MRI lesion activity than either drug alone. Also, the protocol-defined annualized relapse rate (ARR) was lower in the glatiramer acetate arm than in the interferon beta-1a arm. However, other important outcomes showed no differences between arms, thus raising doubts about the importance of the observed differences. For example, there were no between-arm differences in Expanded Disability Status Scale or Multiple Sclerosis Functional Composite worsening or in normalized CSF volume, a measure of brain atrophy. The magnitude of ARR difference between glatiramer acetate (0.10) and interferon beta-1a (0.15) was small.
Generally, the benefits of the combination, compared with monotherapy, seem insufficient to warrant changing clinical practice. Despite that result, there is still much to be learned from the trial. CombiRx is one of the largest cohorts of early relapsing-remitting MS patients studied rigorously for so many years. Data collected during the trial offer an opportunity to correlate biologic and imaging changes with subsequent MS progression. Those studies could provide crucial insights into the MS disease process.
—Richard A. Rudick, MD
Vice Chairman, Research and Development
The Neurological Institute
Director, the Mellen Center
Cleveland Clinic Foundation