Comparative assessment of leflunomide and methotrexate for the treatment of rheumatoid arthritis, by dynamic enhanced magnetic resonance imaging

Abstract

Objective. Ethical constraints on the conduct of placebo-controlled trials evaluating new therapies for serious chronic diseases, such as rheumatoid arthritis (RA), indicate the need for discerning methods to assess treatment effect in active-controlled clinical trials. Dynamic gadolinium-enhanced magnetic resonance imaging (DEMRI) is a sensitive technique for the detection of synovial inflammation in RA. Therefore, this investigation was undertaken to evaluate DEMRI as an efficacy assessment tool for differentiating treatment effect in a randomized, active-controlled trial comparing leflunomide and methotrexate.Methods. Patients with active RA (n ‫؍‬ 39) were randomized in a 2-center, prospective, double-blind clinical trial to receive either leflunomide (n ‫؍‬ 18) or methotrexate (n ‫؍‬ 21) therapy for 4 months. DEMRI scans were obtained at baseline and at 4 months, and the initial rate of enhancement (IRE) and the maximal signal intensity (SI) enhancement (ME) were calculated from the SI curves. Clinical improvement was assessed by conventional outcome measures.Results. Thirty-four patients (17 treated with leflunomide and 17 with methotrexate) had usable baseline and end point DEMRI scans. Leflunomide treatment was associated with a significantly greater improvement in IRE compared with methotrexate treatment (P < 0.05). Average values of ME indicated reduction of inflammation with both leflunomide and methotrexate. The improvement in clinical signs and symptoms, as measured by traditional assessments, was comparable for both active treatments.Conclusion. Results of this study validate the sensitivity of DEMRI in detecting inflammatory changes in active RA in response to treatment. Improvement in synovial inflammation as measured by IRE was significantly better with leflunomide than with methotrexate over 4 months of therapy.

Efficacy and safety of leflunomide alone and in combination with methotrexate in the treatment of refractory rheumatoid arthritis

“…With leflunomide alone for three enhancement by dynamic gadoliniumtreatment and financial constraints, months, EULAR criteria showed improvement enhanced magnetic resonance imaging, have leflunomide can be considered an effective in 6 (54%) and remission in 1 (9%), supported its efficacy. [23,[24][25][26] It was shown to and safe option in the Indian population in respectively. With combination for three be effective and safe in general practice.…”

Extremity magnetic resonance imaging in rheumatoid arthritis: Report of the american college of rheumatology extremity magnetic resonance imaging task force

“…In a trial of 39 patients randomized to receive leflunomide or methotrexate therapy for 4 months, MRI showed greater improvement (reduction), compared with the initial rate of enhancement, in the leflunomide group (38). However, clinical outcomes were comparable in the 2 groups over the same time period.…”

The active metabolite of leflunomide, A77 1726, increases proliferation of human synovial fibroblasts in presence of IL-1β and TNF-α

“…Recently, an analysis by dynamic gadolinium enhanced magnetic resonance imaging (DEMRI) of synovial tissue in patients with RA treated with leflunomide, showed a significant reduction in the initial rate of enhancement and maximal enhancement [30]. DEMRI provides a measure of blood perfusion, capillary permeability and extracellular volume, all of which reflect the inflammatory process of synovitis.…”