Comparative Studies of Glatiramer Acetate and Interferon Beta (Editorial‪)‬

Nevertheless, despite a broad similarity in the therapeutic benefit conferred by each of the different DMTs, the comparative benefit (or side-effect profile) of the different agents is difficult to discern by any attempt to compare outcome across the different RCTs. Thus, different RCTs typically differ in the exact methodology employed, in the MS population targeted, in the baseline characteristics of the enrolled patients and in the behaviour of the placebo group during the trial. Because of these differences, cross-trial comparisons often give radically different views of the comparative efficacy depending upon whether one uses either relative or absolute risk reductions to characterize the difference between agents. As one example, the 29% relative reduction in Gd-enhancing activity using GA (4) is the smallest MRI effect for any of the currently available DMTs. By contrast, when analyzed as an absolute risk reduction, GA therapy has the largest MRI effect of any DMT by a considerable margin. (12) Indeed, given such potentially wide disparities, it is unreasonable to expect that any cross-trial comparison will give an accurate estimate of relative efficacy. Moreover, in addition to uncertainty about whether to emphasize relative or absolute risk reductions, there is also uncertainty about which (if any) of these short-term outcomes correlates significantly with the long-term disability experienced by patients. At the moment, these relationships are not particularly well defined, although in the long-term follow-up study of the original IFNB-1b study, (13) the clinical outcomes of attack rate and disability seemed most closely coupled to physical disability, whereas MRI measures seemed more closely coupled to cognitive outcome. (13) As a result of these considerations it is clear that any accurate assessment of relative efficacy will require a head-to-head study design in which treatment-naive patients are randomized to receive one or the other of the two treatments being compared. Prior to the recent release of the REGARD and the BEYOND study results, (14,15) the only two head-to-head studies in relapsing MS have met, for all or some of their endpoints, the criteria for Class I evidence (16) and, therefore, provide an opportunity to directly assess relative efficacy. (17-20)