Rheumatoid Arthritis: Comparison of Active Therapies in Patients With Active Disease Despite Methotrexate Therapy
Status:
Completed
Trial end date:
2012-05-01
Target enrollment:
Participant gender:
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints leading to joint
destruction, with significant long-term morbidity and mortality. Early treatment of RA
patients with disease-modifying antirheumatic drugs (DMARDs) significantly decreases these
complications. Methotrexate (MTX) is an excellent, economical first-line DMARD used to treat
a majority of RA patients. While most patients respond well to MTX, many continue to have
active disease. Therefore, understanding how to best treat RA patients with active disease
despite MTX therapy is critically important. Although a number of therapies with
significantly different economic implications have been shown to be effective when added to
MTX, no trial has directly compared active therapies. This study will compare therapeutic
strategies using two regimens with proven efficacy when added to MTX therapy; a)
hydroxychloroquine and sulfasalazine (cost ~ $1000 per year); b) the tumor necrosis factor
inhibitor, etanercept (cost ~ $12,000 per year).
We propose a bi-national multi-center randomized, double-blind equivalency trial comparing
(A) the strategy of initially adding hydroxychloroquine and sulfasalazine to MTX in patients
with active disease despite MTX, with a switch at 24 weeks to etanercept in nonresponders to
(B) a strategy of adding etanercept to MTX, with a switch to hydroxychloroquine and
sulfasalazine in nonresponders at 24 weeks. If we find that the strategy of first adding
hydroxychloroquine and sulfasalazine to MTX identifies a subset of responsive patients and
that there is no harm to nonresponders because of early rescue with etanercept, then this
less expensive option should become the standard treatment for MTX resistant patients.
Four hundred and fifty RA patients with active disease despite treatment with MTX as
indicated by a Disease Activity Score with 28 joints (DAS28) of >4.4 units will be
randomized. A DAS improvement of <1.2 (validated as clinically significant) at 24 weeks will
be used to identify early nonresponder who will switch therapy. Subjects with a DAS28
improvement of > 1.2 at 24 weeks will remain on their initial therapy. The primary endpoint
is the change of DAS 28 scores from baseline to 48 weeks. The secondary endpoint is
comparison of radiographic progression of disease at 48 weeks, as measured by the change in
Sharp score. Economic and functional outcomes will be assessed and a serum and DNA bank will
be established to evaluate potential biomarkers predictive of treatment response/toxicity and
disease progression. This trial will recruit 450 subjects over 40 months. At the end of the
48 week blinded active therapy portion of the trial, the blind will be broken and data will
be collected in an open fashion until all 450 patients have completed the 48 week portion of
the trial.
Phase:
N/A
Details
Lead Sponsor:
US Department of Veterans Affairs VA Office of Research and Development
Collaborators:
Canadian Institutes of Health Research (CIHR) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Rheumatoid Arthritis Investigational Network (RAIN)