Unterschiedliche Wirkung der Immuntherapie auf Schübe und schleichende Progression bei Multipler Sklerose: Deutung und Konsequenzen für die Therapie

Zusammenfassung

Die Wirksamkeit verschiedener Substanzen auf Schubparameter ist bei Patienten mit schubhaft remittierender Multipler Sklerose (MS) gut belegt. Patienten mit progredienten MS-Verläufen profitieren dagegen von Immuntherapie kaum. Gegenwärtig wird daher der Behandlungsbeginn nach dem ersten Schub propagiert, auch mit dem Ziel, Degeneration und Behinderung entgegenzuwirken. In der vorliegenden Übersicht wird diese Vorstellung einer kritischen Prüfung unterzogen. Tatsächlich gibt es keine Evidenz, dass durch frühen Beginn einer Immuntherapie die sekundäre Progression verzögert oder abgeschwächt werden kann. Ausgedehnte Degeneration lässt sich früh im Krankheitsverlauf und unabhängig von Entzündungsaktivität fassen. Autoimmunität per se stellt offensichtlich kein ausreichendes pathogenetisches Konzept für MS dar. Alternativ wird ein Virus-Superantigen-Dualismus als Ursache der unterschiedlichen Pathomechanismen der MS vorgestellt. Zusammenfassend ist eine Evidenz-basierte Immuntherapie an der tatsächlichen Entzündungsaktivität der Erkrankung auszurichten. Geeignet ist dafür insbesondere der Abstand zwischen zwei Schüben.

Abstract

It is well established that relapses can be suppressed by different substances in patients with relapsing-remitting multiple sclerosis (MS). In contrast, patients with progressive forms of MS do hardly respond to immune therapy. Therefore, start of immune therapy after the first relapse has been proposed, especially in order to prevent degeneration and disability. This view is challenged in the present review. Actually no evidence exists in support of a retardation or an attenuation of secondary progression by early immune therapy. Widespread degeneration occurs early and progresses independently from inflammatory plaques. Therefore, autoimmunity per se is no adequate paradigm to explain MS-pathogenesis entirely. A virus/superantigen-dualism is proposed to explain the different parts of MS, instead. It is concluded that evidence-based immune therapy should be adapted to the actual inflammatory activity of the disease. A suitable parameter for this purpose is the interval between 2 relapses.

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