Remission Induction in Very Early Rheumatoid Arthritis
Status:
Unknown status
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
Rheumatoid arthritis (RA) is a debilitating chronic immune mediated inflammatory disease
which affects 1% of the European population. RA is associated with significant joint damage,
disability and an enhanced mortality. Current treatment strategies target patients once
synovitis has been present for several months and it is clear that the patient has developed
persistent disease. After the first 3 months of symptoms, we and others have shown that the
persistence of chronic inflammation in the rheumatoid synovium is driven by hyperplastic
stromal tissue which inhibits leukocyte apoptosis leading to the accumulation of inflammatory
cells in the joint. Therapies at this stage of disease, with conventional disease modifying
anti-rheumatic drugs (DMARDs) as well as drugs targeting TNF-alpha reduce disease activity
but are unable to cure RA. We have now identified that the very early phase of synovitis in
patients destined to develop RA (within the first 12 weeks of symptoms) represents a
pathologically distinct phase of disease. This suggests that late disease is not just more of
early disease and gives, for the first time, a clear rationale for very early intervention.
Building on these recent observations, we propose to test the hypothesis that the disease
processes in the very early stages of RA are fundamentally different to those in established
chronic disease. This will be done by assessing whether treatment during this phase with the
well-established gold standard modality of anti-TNF-alpha therapy and methotrexate can
permanently switch off inflammation, preventing the development of RA and thereby effecting a
cure of the disease.