Scandinavian journal of rheumatology. Supplement最新文献

The efficacy and safety of the novel DMARD leflunomide was compared to placebo and sulfasalazine in a randomized, double-blind study. At Week 24, leflunomide significantly reduced tender and swollen joint counts and physician and patient assessment scores compared to placebo (P < 0.001). Response rates with leflunomide were significantly greater than placebo: ACR 20% (55% vs 29%, P = 0.0001). Comparable response rates were observed with sulfasalazine (ACR 20%: 56%). Leflunomide significantly improved HAQ scores compared to placebo or sulfasalazine (P < 0.009). The onset of action with leflunomide was rapid and was seen as early as Week 2. Radiographic disease progression was significantly slower with leflunomide than placebo (P < 0.01). Leflunomide was well tolerated. No long-term safety issues were reported with leflunomide in patients who opted to continue treatment for up to 2 years. Efficacy of leflunomide in the treatment of RA was maintained at 2 years.

This paper compares and contrasts the results of two major Phase III clinical trials that compared the efficacy and safety of leflunomide, a new disease-modifying antirheumatic drug (DMARD), and methotrexate. In both the American trial (US301) and the multinational trial (MN302), patients with active rheumatoid arthritis (RA) were given either leflunomide (20 mg/day after a loading dose of 100 mg/day for 3 days) or methotrexate (7.5-15 mg/week) for 52 weeks. US301 was also placebo-controlled. Folate supplementation was mandatory in US301 but was given to < 10% of the patients in MN302. In US301, American College of Rheumatology (ACR) 20% response rates and improvement in tender and swollen joints were significantly better than placebo in both treatment groups, but were not significantly different from each other. Both treatments significantly retarded radiographically assessed progression of RA compared to placebo, but the degree of retardation was significantly greater with leflunomide. In MN302, the ACR response rate and improvement in tender and swollen joints with leflunomide were similar to those seen in US301. The ACR response rate and improvements in all efficacy variables with methotrexate were significantly greater than with leflunomide, however. Radiographically assessed disease progression was not statistically different with the two treatments. Use of methotrexate without folate in MN302 was associated with a higher incidence of clinically significant elevations of liver enzyme levels. These results indicate that both leflunomide and methotrexate are effective DMARDs. The symptomatic relief provided by both drugs is similar when they are given with folate supplementation.

Several currently available nonsteroidal anti-inflammatory drugs (NSAIDs) have been evaluated for their relative selectivity in inhibiting the two cyclooxygenase (COX) isozymes, COX-1 and COX-2. Arguments have been made that more selective inhibitors of COX-2 will be safer than less selective ones. Rankings of the COX-2/COX-1 inhibition ratios of various NSAIDs as they relate to the agents' toxicities have been used as evidence that COX-2 selectivity is an important factor in the upper gastrointestinal (GI) safety of some NSAIDs. Unfortunately, none of these claims has been supported by endoscopy studies in treated patients. Since all NSAIDs inhibit COX-1, they all cause upper GI mucosal damage. What is needed are specific COX-2 inhibitors that do not inhibit COX-1. Such agents are currently under development. Ongoing clinical trials will determine the potential role for specific COX-2 inhibitors in the treatment of arthritis and pain. If specific COX-2 inhibitors are shown to be both safe and effective, the treatment of rheumatic diseases will be revolutionized.

The aim of the study was to investigate the reliability and the validity of the Swedish version of the Bath Ankylosing Spondylitis Functional Index (BASFI). A total of 113 patients were assessed with the BASFI, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Metrology Index (BASMI), and the Bath Ankylosing Spondylitis Patient Global Score (BAS-G). The median BASFI scores on two occasions within 24 hours were 3.6 versus 3.7 (p>0.05). The patients found the BASFI items relevant. The median self-reported and physiotherapist-observed BASFI scores were 3.4 and 2.8 respectively (p>0.05). The correlation coefficient between the BASFI and the BASMI was r(s)=0.55, between the BASFI and the BASDAI r(s)=0.68, and between the BASFI and the BAS-G r(s)=0.67. Significant improvements between the pre- and post-training results for both the BASFI (3.1 vs 2.0, p<0.001) and the BASMI (3.0 vs 1.0, p<0.001) were found after three weeks' inpatient rehabilitation. The results indicated that the Swedish BASFI is reliable and valid.

Rheumatoid arthritis (RA) is characterized by chronic inflammation and irreversible destruction of articular cartilage and bone. Disease progression as assessed by radiographic imaging of structural joint damage is a key outcome measure in RA. Joint damage is especially rapid during early phases of RA, thus the current trend of early aggressive therapy with disease-modifying antirheumatic drugs (DMARDs). Radiographic analysis of disease progression with the novel DMARD leflunomide was compared to methotrexate and sulfasalazine in two large, placebo-controlled, randomized Phase III studies (N = 580). The results as indicated by changes in x-ray scores indicate that leflunomide and both active comparators slow disease progression significantly better than placebo (P < or = 0.01). Slowing of disease progression with leflunomide was similar to sulfasalazine at 6 months but better than methotrexate (P < or = 0.049) at 12 months. These data verify the ability of leflunomide to slow disease progression and confirm its disease-modifying potential.