Leflunomide Group Research Articles

Examination of the Risk of Continuous Leflunomide Treatment on the Incidence of Infectious Complications After Joint Arthroplasty in Patients With Rheumatoid Arthritis

To determine whether the risk of infectious complications after total joint arthroplasty is increased in rheumatoid arthritis patients who are treated continuously with leflunomide, the incidences of infectious complications in 41 rheumatoid arthritis patients who received continuous leflunomide treatment (leflunomide group) and in 41 patients who did not receive leflunomide within 4 weeks of surgery (nonleflunomide group) were compared. The incidence (6.1%) of local infection after surgery in the leflunomide group (82 procedures) was slightly lower than that (6.3%) in the nonleflunomide group (79 procedures). There were no systemic or deep infections. None of the other variables analyzed were identified as risk factors for postoperative complications. The results indicate that there is no dramatically increased risk of postoperative infectious complications in rheumatoid arthritis patients who continue to be treated with low doses of leflunomide perioperatively.

Leflunomide for treating rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. Leflunomide, as an inhibitor of pyrimidine synthesis, has a different mechanism of action than other existing disease modifying anti-rheumatic drugs (DMARD). To determine the efficacy and toxicity of leflunomide compared to placebo or other DMARDs in the treatment of RA. We conducted a search in MEDLINE, EMBASE, Current Contents and the Cochrane Controlled Trial Register for trials up to December 2001. We also hand-searched reference lists and consulted content experts. Two independent reviewers selected the trials that met predetermined inclusion criteria. Two independent reviewers extracted data and assessed methodologic quality using standardized forms. Six trials were included in this review. Using the ACR20 improvement criteria, there was an absolute difference in improvement of 28% (95% confidence interval: 21 - 35%) favouring leflunomide (232 out of 413 leflunomide treated patients compared to 89 out of 311 placebo patients met the criteria). There was no difference in ACR20 response rate between the patients treated with leflunomide and SSZ or MTX at 6 and 12 months. Other clinical outcomes were improved significantly in the leflunomide group compared to placebo but not different from SSZ or MTX. Withdrawals due to adverse events with leflunomide were 10% greater than placebo (70 out of 416 compared to 18 out of 311 respectively). Important adverse events included gastrointestinal symptoms, elevated liver function tests, alopecia, and infections. Overall adverse events and withdrawals in the leflunomide group were not significantly different from SSZ or MTX. Leflunomide appears to improve all clinical outcomes and delay radiologic progression at both 6 and 12 months of treatment compared to placebo. Its efficacy and adverse events at 2 years of treatment are comparable to SSZ and MTX. Long-term efficacy and toxicity remains to be established.

Traitement de la polyarthrite rhumatoïde par une dose hebdomadaire de leflunomide. Étude ouverte comparative

Aims. To assess the therapeutic effect of leflunomide in weekly dose of 100 mg in patients with refractory rheumatoid arthritis. Methods. Sixteen patients were included (18-72 years, disease duration 2-32 years). Eight patients received a weekly dose of 100 mg of leflunomide and 8 the conventional dose. Current treatment was not modified. All patients underwent a monthly evaluation for one year, applying the 1995 ACR preliminary definition of improvement in rheumatoid arthritis. Results. After 2 months, the group treated with the conventional leflunomide dose evidenced a remarkable improvement (7/8 patients achieving ACR 20), while the group receiving the weekly dose, the improvement was not as clearly evident (3/8 patients achieving ACR 20). By the fourth to sixth month, the response was comparable on both groups (6/6 and 6/8 patients achieving ACR 50 in the daily and weekly dose, respectively) and prevailed through the end of the study. There were no statistical differences between groups at any evaluation. Side effects made itself clear in 6 patients in the daily leflunomide group, and 2 patients withdrawn leflunomide because severe gastrointestinal symptoms and hepatotoxicity, respectively. In the group of weekly leflunomide 2 patients presented side effects which disappeared spontaneously. Conclusion. The use of leflunomide in a weekly dose of 100 mg proved to have similar therapeutic benefit as that of the conventional scheme and might represent a new option for the treatment of refractory rheumatoid arthritis patients.

Weekly dose of leflunomide for the treatment of refractory rheumatoid arthritis: an open pilot comparative study

Aims. To assess the therapeutic effect of leflunomide in weekly dose of 100 mg in patients with refractory rheumatoid arthritis. Material and Methods. Sixteen patients were included (18-72 years, disease duration 2-32 years). Eight patients received a weekly dose of 100 mg of leflunomide and 8 the conventional dose. Current treatment was not modified. All patients underwent a monthly evaluation for one year, applying the 1995 ACR preliminary definition of improvement in rheumatoid arthritis. Results. After 2 months, the group treated with the conventional leflunomide dose evidenced a remarkable improvement (7/8 patients achieving ACR 20), while the group receiving the weekly dose, the improvement was not as clearly evident (3/8 patients achieving ACR 20). By the fourth to sixth month, the response was comparable on both groups (6/6 and 6/8 patients achieving ACR 50 in the daily and weekly dose, respectively) and prevailed through the end of the study. There were no statistical differences between groups at any evaluation. Side effects made itself clear in 6 patients in the daily leflunomide group, and 2 patients withdrawn leflunomide because severe gastrointestinal symptoms and hepatotoxicity, respectively. In the group of weekly leflunomide 2 patients presented side effects which disappeared spontaneously. Conclusion. The use of leflunomide in a weekly dose of 100 mg proved to have similar therapeutic benefit as that of the conventional scheme and might represent a new option for the treatment of refractory rheumatoid arthritis patients.

Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial

Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis. 358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat. The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were significantly superior to placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic disease progression was significantly slower with leflunomide and sulphasalazine than with placebo (p<0.01). Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnormal liver function was seen in three leflunomide-group patients and five sulphasalazine-group patients. There were two cases of reversible agranulocytosis in the sulphasalazine group. Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a disease-modifying antirheumatic drug.