Caster Ola, Edwards I Ralph
Uppsala Monitoring Centre (UMC), Box 1051, SE-751 40, Uppsala, Sweden.
Department of Computer and Systems Sciences, Stockholm University, Postbox 7003, SE-164 07, Kista, Sweden.
BMC Neurol. 2015 Oct 16;15:206. doi: 10.1186/s12883-015-0450-x.
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 2000 mg and less than 1000 mg, respectively, during at most 31 days) and a no treatment alternative, with the aim of determining which regimen, if any, is preferable in multiple sclerosis relapses.
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.
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.
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.
高剂量短期甲基泼尼松龙是多发性硬化症复发管理中的推荐治疗方法，尽管有人认为较低剂量可能同样有效。此外，糖皮质激素与多种且通常与剂量相关的不良反应有关。这项定量效益风险评估比较了高剂量和低剂量甲基泼尼松龙（分别在最多31天内至少2000毫克和少于1000毫克）以及不进行治疗的替代方案，目的是确定在多发性硬化症复发中哪种方案（如果有的话）更可取。
应用概率决策分析的总体框架，结合来自不同来源的数据。从已发表的临床试验中估计有效性以及非严重不良反应的风险。然而，由于这些试验记录的严重不良反应很少，后者的风险区间来自个别病例报告以及一系列合理的分布。由逻辑隐含或临床动机良好的定性关系驱动的概率建模用于推导效用分布。
在这项评估中，低剂量甲基泼尼松龙不是一个支持的选择；然而，这种治疗替代方案仅有有限的数据可用。高剂量甲基泼尼松龙和不治疗替代方案交替成为最优选的方案，这取决于应用于严重不良反应的风险分布、患者群体中假设的风险厌恶水平以及复发的严重程度。
目前可用的数据不支持改变当前的治疗建议。有强烈的动机进行进一步的临床研究，以减少围绕甲基泼尼松龙在多发性硬化症复发中的有效性和相关风险的不确定性；这将使未来能够做出更明智、更精确的治疗建议。
