Preserved in vivo response to interferon-alpha in XXXX @entity1 with neutralising antibodies against interferon-beta (REPAIR study).

@entity1 @entity5438 @entity2205 @entity2391 @entity13434 @entity688 @entity15 @entity3027
BACKGROUND: A major problem in the treatment of @entity15 ( @entity15 ) @entity1 with interferon-beta ( @entity2391 ) is the development of neutralising antibodies (NAbs). High levels of NAbs block the induction of @entity2391 -inducible markers, including Myxovirus Resistance Protein A (encoded by the @entity13434 gene), resulting in a loss of bioactivity and therapeutic benefit. OBJECTIVE: The primary objective of this study is to investigate the in vivo biological response to interferon-alpha ( @entity3027 ) in @entity15 @entity1 , who have developed neutralising antibodies (NAbs) against @entity2391 . DESIGN/METHODS: The study was an open-label phase II study in 10 @entity1 with relapsing-remitting @entity15 with persisting NAbs against @entity2391 and absent in vivo mRNA MxA response. We used in vivo induction of @entity13434 mRNA and other IFN-inducible genes as measure of the biological response. The primary endpoint was the in vivo mRNA @entity13434 response after an injection of @entity3027 compared with the response after an injection of @entity2391 . RESULTS: In all 10 @entity1 we found high @entity13434 expression after injection of @entity3027 6 MIU, indicating a preserved in vivo response to @entity3027 . We measured the gene expression index of immune system genes in blood cells from the 10 NAb-positive @entity1 after @entity3027 treatment and 10 NAb-negative @entity1 after injection of @entity2391 . We found a significantly increased expression of a number of genes, including @entity13434 , @entity5438 , @entity688 and @entity2205 (encoding @entity2205 ) in the NAb-positive @entity1 treated with @entity3027 . INTERPRETATION: @entity3027 could be a therapeutic option in @entity1 , who have lost the biological response to @entity2391 because of NAbs against @entity2391 . ClinicalTrials gov. Identifier: NCT01171209.
