Sulfasalazine in early rheumatoid arthritis. A 48‐week double‐blind, prospective, placebo‐controlled study

103

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.

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confidence: 99%

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

Reece¹,

Kraan²,

Radjenovic³

et al. 2002

103

“…Increasing information has demonstrated that DMARDs such as cyclosporin A (14), sulfasalazine (15,16), and methotrexate (17) reduce cartilage and bone destruction. Leflunomide is a recently developed DMARD that effectively reduces joint inflammation and its deleterious effects on joint integrity (16)(17)(18).…”

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confidence: 99%

Modulation of inflammation and metalloproteinase expression in synovial tissue by leflunomide and methotrexate in patients with active rheumatoid arthritis: Findings in a prospective, randomized, double-blind, parallel-design clinical trial in thirty-nine patients at two centers

Kraan

Reece

Barg

et al. 2000

152

101

Objective. Leflunomide and methotrexate have proven to be efficacious in reducing joint inflammation and slowing destruction in clinical trials of patients with rheumatoid arthritis (RA). This study was conducted to provide more insight into the mechanism of action of these agents in synovial tissue.Methods. In a 2-center, prospective, randomized, double-blind clinical trial, we compared leflunomide (20 mg/day, after a 3-day 100 mg/day loading dose) and methotrexate ( Conclusion. Leflunomide and methotrexate are clinically efficacious drugs that interfere with mechanisms involved in joint inflammation and destruction of joint integrity.

“…The 34 patients whose conditions had deteriorated to classes 111-IV were treated, on average, with >4 SAARDs within 5 years. In contrast, the patients in whom remission had been 8 (6) 43 (30) 28 (20) 25 (17) 38 (27) 30 (21) 64 (45) 40 (28) 8 (6) achieved had used an average of <2 SAARDs ( Figure 1). SAARD terminations in patients in Steinbrocker classes IJI-IV were more often due to inefficacy (mean 2.7 SAARDs) than to adverse events (mean 1.0 SAARDs) .…”

Section: Resultsmentioning

confidence: 99%

“…ever, that slow-acting antirheumatic drugs (SAARDs) can alter the short-term course of RA (4)(5)(6)(7). Long-term outcome in most RA patients appears to be poor, however, and SAARDs have not been found to be capable of modifying it (3,s-13).…”

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confidence: 99%

Outcome in patients with early rheumatoid arthritis treated according to the “sawtooth” strategy

Möttönen¹,

Paimela²,

Ahonen³

et al. 1996

Self Cite

Objective. To investigate the outcome of early rheumatoid arthritis (RA) when treated according to the “sawtooth” strategy, and to compare the results with the findings of other studies. Methods. In this prospective study, 142 patients with early RA were treated actively with slow‐acting antirheumatic drugs (SAARDs) for an average of 6.2 years, and were closely monitored clinically. Several outcome measures were applied, and the results were compared with findings in previously described cohorts. Results. The mean cumulative number of SAARDs used during the study was 3.3. Treatment changes were made because of inefficacy more often than because of adverse events. The percentage of patients whose disease entered remission increased with time to 32% (45 of 142). Only 24% of the patients (34 of 142) had deterioration to Steinbrocker functional class III or IV. The “sawtooth” treatment strategy seemed to improve the outcome of the patients with early RA. Conclusion. In the majority of patients with early RA, “sawtooth” therapy remains beneficial for at least 6 years. However, in one‐fourth of the patients, the disease fails to respond to this drug treatment strategy.