Intra-articular etanercept treatment in @entity625 : A randomized double-blind placebo-controlled proof of mechanism clinical trial validating XXXX as a potential therapeutic target for local treatment.

@entity1 @entity32 @entity625 @entity310 @entity5144 @entity309
OBJECTIVE: There is an increased interest in developing gene therapy approaches for local delivery of therapeutic genes in @entity1 with @entity625 . Intra-articular (i.a.) gene delivery, using an adeno-associated virus encoding a @entity310 soluble receptor, resulted in reduced paw swelling in an @entity625 animal model, but i.a. treatment with a similar vector did not induce robust clinical improvement in @entity1 . It is unclear whether this can be explained by for instance insufficient transduction efficiency or the fact that @entity310 is not a good therapeutic target for i.a treatment. The objective of this study was to explore the effects of i.a @entity310 blockade. METHODS: Thirty-one @entity1 with @entity309 or @entity5144 were assigned to a single i.a. injection of 25mg etanercept or placebo in a double-blind randomised controlled clinical trial. The primary end point was target joint improvement, determined by a composite change index. RESULTS: Twenty-two @entity1 received etanercept and 9 received placebo. Treatment was generally well tolerated. Treatment with etanercept resulted in a prompt and statistically significant improvement of the index (P<0.001) in comparison with placebo. As expected in light of the half-life of etanercept, the beneficial effect was transient and only statistically significant at week 1 and 2 after i.a. injection. CONCLUSION: The results support the development of novel approaches for long-term inhibition of @entity310 at the site of @entity32 , such as gene therapy. TRIAL REGISTRATION: The Netherlands National Trial Register (NTR), www.trialregister.nl, NTR-1210.
