A Cochrane review (abstract , review ) included 33 studies. 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 sulfasalazine (SSZ) or methotrexate (MTX). The efficacy of leflunomide combined with MTX was superior to MTX alone. On the other hand, leflunomide plus SSZ was not better than SSZ alone. Half-dose or weekly administration of leflunomide was shown to be as efficacious as regular doses (20 mg/day).
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, allergic reactions and rashes, and infections. Overall adverse events and withdrawals in the leflunomide group were not significantly different from SSZ or MTX. However, adverse events were reported more frequently in leflunomide plus MTX than with MTX but withdrawal rates were not significantly different.
A systematic review including 3 studies with a total of 1242 subjects was abstracted in DARE. Leflunomide (LFM) therapy was demonstrated to be significantly superior to placebo in relation to the efficacy outcome measures, e.g. tender joint count, swollen joint count, patient and physician global assessment, pain, erythrocyte sedimentation rate and C-reactive protein. In addition, it slowed the radiological progression of RA in three studies.
LFM treatment was comparable to sulphasalazine (SSZ) and methotrexate (MTX) with respect to efficacy, radiological progression and quality of life measures. LFM was found to have a somewhat faster onset of action and provide a slightly longer duration of sustained response.
The percentage of study withdrawals due to lack of efficacy was lower for the LFM groups than for either SSZ or MTX. The most common adverse effects leading to withdrawal from LFM treatment were gastrointestinal symptoms (rash and pruritus), alopecia, dyspepsia, hypertension, and elevated transaminase levels. Weight loss and dizziness have also been reported for LFM treatment.
The authors state that, despite the small number of published articles relating to LFM treatment, the evidence suggests that LFM is significantly superior to placebo and similar in efficacy to both SSZ and MTX, although with a differential pattern of side-effects. LFM therapy costs about $1,000 per annum, approximately $400 more than SSZ and $300 more than MTX.