Wiener Medizinische Wochenschrift

, Volume 158, Issue 3–4, pp 98–109

Interferon-Beta-1a subkutan in der Behandlung der Multiplen Sklerose

Themenschwerpunkt
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Zusammenfassung

Rekombinantes IFN-β-1a subkutan wurde in verschiedenen Stadien der Multiplen Sklerose – CIS, RRMS und SPMS – gut im Rahmen von multizentrischen, randomisierten und plazebokontrollierten Studien, die alle als Klasse-1-Evidenz bewertet werden können, im Laufe der letzten zehn Jahre untersucht. Die immunmodulatorische Wirkung von IFN-β-1a subkutan auf den Krankheitsverlauf der MS ist für klinische Endpunkte gut und für die subklinische Krankheitsaktivität anhand von MRI-Parametern sehr gut belegt. Als Charakteristikum von IFN-β-1a subkutan wurde konsequent am Beleg einer Dosis-Wirkungs-Beziehung gearbeitet, die nun das Schema mit 3 × 44 µg pro Woche subkutan als wirksamstes unter den IFN-β-1a-Behandlungsalternativen bei RRMS zeigt. Allerdings wird die stärkere Wirksamkeit letztlich doch um den Preis einer höheren Immunogenität und vermehrter lokaler Hautreaktionen an der Injektionsstelle erkauft. Derzeit kann aus den umfangreichen Daten zur Dosis-Wirkungs-Beziehung von IFN-β bei RRMS dennoch keine primäre Behandlungsempfehlung für ein Präparat abgeleitet werden, weil bei einer Langzeittherapie neben der Wirksamkeit sowohl die Immunogenität mit dem Risiko des Wirkverlustes durch neutralisierende Antikörper als auch die individuelle Präferenz der Applikationsform des Immunmodulators eine wesentliche Rolle spielen. IFN-β-1a subkutan scheint nicht depressionsfördernd zu wirken. Eine Depression bei MS-Patienten korreliert mit dem Behinderungsausmaß und der Krankheitsdauer, nicht aber mit der Dosis von IFN-β. Ebenso gibt es keine Hinweise auf Teratogenität von IFN-β-1a, bei 69 dokumentierten Schwangerschaften in den klinischen Studien zeigten sich nur Hinweise auf eine eventuell etwas erhöhte Abortrate. Dennoch muss für MS-Patientinnen weiterhin eine Kontrazeption unter IFN-β-Therapie im gebärfähigen Alter empfohlen werden. Im Langzeitverlauf der Therapie bleiben Wirksamkeit und Sicherheit auch über bis zu acht Jahre erhalten, wobei die Daten zur Vermeidung der Behinderungsprogression wegen einer drop-out-Rate von etwa 30 % nicht eindeutig sind. Im Übrigen war IFN-β-1a subkutan über viele Jahre gut verträglich, was auch durch den 50-Prozent-Anteil langfristig adhärenter Patienten in der Langzeitbeobachtung untermauert wird. Die Beeinflussung der in letzter Zeit zunehmend in den Vordergrund rückenden kognitiven Defizite bei MS – Aufmerksamkeitsstörungen, Beeinträchtigung der Exekutivfunktionen und "chronic fatigue" – wurde in den bisherigen Studien zu IFN-β-1a subkutan nicht untersucht.

Schlüsselwörter

Multiple Sklerose CIS RRMS SPMS Interferon-Beta-1a Neutralisierende Antikörper Schwangerschaft Depression MRI 

Subcutaneous interferon-beta-1a in the treatment of multiple sclerosis

Summary

During the last 10 years recombinant interferon-beta-1a administered subcutaneously has been the subject of several clinical trials in relapsing remitting multiple sclerosis (RRMS), in secondary progressive MS (SPMS), as well as in clinically isolated syndromes. All of them met the criteria of evidence level class I. Consistent evidence for moderate immunomodulatory effects on clinical parameters of disease activity was gained, and even higher efficacy of IFN-β-1a sc. on MRI activity of multiple sclerosis was proven. Indirect evidence confirmed the hypothesis of a dose-response curve for IFN-β-1a formulations in MS. The higher efficacy of IFN-β-1a 44 µg sc. TIW, however, also includes more adverse events such as injection site reactions, flu-like symptoms and a moderate immunogenicity. Current evidence does not allow a recommendation of IFN-β-1a sc. as most effective first line therapy, because also the individual patient's choice in the route of administration and long-term effects of neutralizing antibodies to IFN-β-1a sc. must be taken into account. In the long-term, IFN-β-1a showed a beneficial safety-tolerability profile with 50 % of patients sticking to the initial immunomodulatory treatment. There were no teratogenic effects, IFN-β-1a sc. did not enhance depressive symptoms. Data on inhibition of the progression of disease, however, remained inconclusive. Probable beneficial effects of IFN-β-1a sc. on cognitive function or "chronic fatigue" have not been investigated yet.

Keywords

Multiple sclerosis CIS RRMS SPMS Interferon-beta-1a Neutralizing antibodies Pregnancy Depression MRI 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Neurologische AbteilungKrankenanstalt RudolfstiftungWienAustralia

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