Background Ineffective control of clinical activity is frequently observed in a subgroup of rheumatoid arthritis (RA) patients that present severe evolution with no response to classical DMARDs isolated or in association.

Objectives To assess the efficacy of leflunomide in difficult RA in a 24-week open-label prospective study.

Methods 20 patients fulfilling ACR diagnosis criteria were selected based on non-response or adverse effects to at least three DMARDS (including methotrexate -MTX). The patients were regularly attending the outpatient clinic for at least 5 years and this study did not bring alterations in their routine care and follow-up. All patients were female, with erosive disease and in clinical activity: mean DAS (disease activity score) = 5.30. Their mean age was 46 years (range 32 to 61) and the mean RA duration was 12 years (range 5 to 27), and FR positive in 19, previous use of at least 3 DMARDs (mean 4; maximum 7). At the beginning of the study chloroquine was currently given to 8 patients, MTX to 13 (mean dose = 19 mg/week; range15–25) and sulfasalazine to 12. Seven patients were receiving azathioprine and only one was on methilprednisolone monthly pulses. All subjects were receiving oral corticosteroids (CE) (mean 10,5 mg/day; range 7,5 to 20 mg) and NSAIDs. While oral dose CE and NSAIDS were maintained, all DMARDS were suspended and Leflunomide administered at the initial dose of 100 mg/day/3 days followed by 20 mg/day, with no washout period. Clinical exams and laboratory tests were performed monthly.

Results After 6 months, 60% of the patients were considered responders achieving ACR >or = 20%. Regarding DAS 28, 75% of the patients were considered responders. CE oral dose was reduced in 7 patients. Adverse effects were observed in 4 patients: diarrhoea in 2; alopecia in 2. Lymphopenia was observed in one patient who was well controlled (ACR50 response) with leflunomide every other day. Only one patient suspended treatment (alopecia plus clinical activity). There was no increase in transaminase enzymes levels. Increase in alkalyne phosphatase levels was observed in 5 patients: in four, increase was mild (< 2 times that of normal range) and in only one > or = 2 times that of normal range.

Conclusion Patients refractory to multiple DMARDS can safely achieve a favourable response with leflunomide.