Escalating therapy in steroid-refractory relapses of multiple sclerosis - comparison of methylprednisolone to immunoadsorption "EMMA"

多发性硬化症的神经功能障碍在很大程度上是由于急性复发后累积的残余缺陷。目前复发的标准治疗是短期高剂量静脉注射甲泼尼龙（IVMP），必要时可以重复使用更高剂量。如果反应不充分，则应用体外程序（血浆置换，PE或免疫吸附，IA）。两者都采用不同的治疗机制，如果在复发过程的早期使用，似乎最有效。然而，目前的做法拖延了它们的使用。IA相对于PE的优势是选择性去除自身抗体/免疫复合物，避免输血及其相关并发症，以及其通过外周静脉插管的常见性能。在这项多中心随机、评价者设盲、2组、平行组试验中，评价了IA相对于第2个IVMP疗程的优效性。将通过ANCOVA分析主要终点-随机化治疗（BoT）开始后第45天（或任何补救治疗前）EDSS评估的神经功能障碍。140例患者的样本将确保>80%的把握度显示IA的优效性，将大于或等于0.5 EDSS分的组差异视为临床相关，并适应报告的异质性或甚至更大。次要终点是EDSS、MSFC、pFS、视敏度（视神经炎）直至第45天和第180天的演变、EoS时的各种QoL和疲劳测量、治疗接受度和应答率。通过（严重）不良事件和进一步的临床相关安全性结果监测临床安全性，并通过精确的Fisher检验进行分析。（重复测量）ANCOVA。

Neurological disability in multiple sclerosis results to a large extent from accumulating residual deficits after acute relapses. Current standard treatment for a relapse is a short course of high-dose intravenous methylprednisolone (IVMP), with repetition at even higher doses if necessary. In case of insufficient response, extracorporeal procedures (plasmapheresis, PE, or immunoadsorption, IA) are applied. Both employ different therapeutic mechanisms and seem to be most effective if used early in the course of the relapse. However, current practice delays their use. Advantages of IA over PE are a selective removal of autoantibodies/immune complexes, avoiding transfusions with their associated complications, and its common performance via peripheral venous cannula. In this multi-centre randomised, evaluator-blinded, 2-armed, parallel-group trial, the superiority of IA over a 2nd IVMP course is evaluated. The primary endpoint - neurological disability by EDSS at day 45 after the beginning of randomised treatment (BoT) (or before any rescue treatment) - will be analysed by ANCOVA. A sample of 140 patients will ensure a power >80% to show superiority of IA, regarding a group difference of greater-than-or-equal 0.5 EDSS points as clinically relevant and accommodating heterogeneity as reported or even somewhat larger. Secondary endpoints are evolution of EDSS, MSFC, pFS, visual acuity (in optic neuritis) until day 45 and 180, various QoL & fatigue measures at EoS, acceptance of treatment, and response rates. Clinical safety is monitored by (serious) adverse events and further clinically relevant safety findings, analysed by exact Fisher-Test resp. (repeated-measures) ANCOVA.