Quantitative benefit-risk assessment of methylprednisolone in multiple sclerosis relapses

Abstract

Background: High-dose short-term methylprednisolone is the recommended treatment in the management of multiple sclerosis relapses, although it has been suggested that lower doses may be equally effective. Also, glucocorticoids are associated with multiple and often dose-dependent adverse effects. This quantitative benefit-risk assessment compares high- and low-dose methylprednisolone (at least 2000mg and less than 1000mg, respectively, during at most 31days) and a no treatment alternative, with the aim of determining which regimen, if any, is preferable in multiple sclerosis relapses. Methods: An overall framework of probabilistic decision analysis was applied, combining data from different sources. Effectiveness as well as risk of non-serious adverse effects were estimated from published clinical trials. However, as these trials recorded very few serious adverse effects, risk intervals for the latter were derived from individual case reports together with a range of plausible distributions. Probabilistic modelling driven by logically implied or clinically well motivated qualitative relations was used to derive utility distributions. Results: Low-dose methylprednisolone was not a supported option in this assessment; there was, however, only limited data available for this treatment alternative. High-dose methylprednisolone and the no treatment alternative interchanged as most preferred, contingent on the risk distributions applied for serious adverse effects, the assumed level of risk aversiveness in the patient population, and the relapse severity. Conclusions: The data presently available do not support a change of current treatment recommendations. There are strong incentives for further clinical research to reduce the uncertainty surrounding the effectiveness and the risks associated with methylprednisolone in multiple sclerosis relapses; this would enable better informed and more precise treatment recommendations in the future.