Seropositive Muskuloskeletal Complaints Clinical Trial
Official title:
Towards Efficient Prediction and Prevention of Rheumatoid Arthritis
Seropositive Rheumatoid arthritis (RA) is characterized by autoantibodies that develop prior
to clinical onset, allowing identification of individuals at risk for disease development. In
a unique program in Stockholm, seropositive individuals presenting with musculoskeletal
complains are currently identified and followed-up in a dedicated outpatient clinical
program. Despite significant disease burden and increased sick leave among these individuals,
we lack today any therapeutic and preventive measures.
We aim to (1). establish a nation-wide health program, (2). develop an algorithm for disease
risk estimation and (3). test a novel strategy to delay and/or prevent disease onset in
seropositive at risk individuals with musculoskeletal complains. We will perform a
multicentre randomised study to treat autoantibody-positive individuals at risk for
developing RA presenting with pain (Population), by repurposing of bisphosphonates
(Intervention) as compared to placebo (Control) to treat pain (primary Outcome) and
delay/prevent RA development during 1-year follow-up (secondary Outcome)
we have recently identified a novel disease-triggering pathogenic mechanism in
autoantibody-positive individuals consisting in a bone-mediated induction of pain by
autoantibodies. We hypothesize that specific targeting of this new mechanism, rather than
using therapies developed for already established disease (where other mechanisms are
active), will be able to treat pain with arthralgia and halt disease progression in
seropositive at-risk individuals.
We will address this hypothesis by repurposing of bisphosphonates, currently used in clinical
practice in both RA patients as well as in many individuals at risk for RA (mainly women in
post-menopausal age). We will perform a multi centre, prospective, randomised, double-blind
and placebo-controlled study with 2 parallel groups.
Patients will be randomised 1:1 to receive either one infusion aclasta (5 mg zolendronic
acid, n=40) or placebo (n=40). The primary outcome is the VAS pain score and the study is
powered to detect a 20% difference in the primary endpoint between the active and the control
arm. The study is powered to detect a 20-percentage point difference in proportions between
the control and the treated group. Subjects may withdraw from the trial at any time at their
own or the investigators request for safety reasons.
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