[Security of the combined treatment of methotrexate and leflunomide in patients with rheumatoid arthritis].

Rheumatoid Arthritis (RA) is a chronic disease leading to functional impairment and early mortality. Treatment with disease-modifying antirheumatic drugs have shown to achieve disease remission and improves its evolution. The use of combined therapy should have a biological efficacy, no increased toxicity and have an acceptable dose interval. Also, it should begin its action quickly and be cost-effective.

OBJECTIVE

to assess the security of the combined treatment with Methotrexate (MTX) and Leflunomide (LF) in patients with Rheumatoid Arthritis (RA) and to evaluate whether the dose and route of MTX administration influence on the toxicity.

METHODS

Patients with RA who fulfilled ACR criteria and they attended to the Rheumatology Unit at Córdoba Hospital in the last 2 years were assessed. All the patients that received combined treatment with MTX in doses from 7.5 mg to 25 mg weekly orally (PO) or intramuscularly (i.m.) that started LF treatment in doses of 20 mg/day due to disease activity persistence were retrospectively assessed. Patients having at least 6 months of combined treatment were included. Data on treatment and adverse events were collected. They were evaluated at the beginning, at 6 and 12 months of treatment. The presence of adverse events as well as the stop of combined treatment was evaluated at 6 and 12 months of treatment. Adverse events in patients with oral and i.m. MTX treatment and in different doses were compared for the analyses. P<0.05 was considered significant.

RESULTS

62 patients with a mean age of 54 were included. 89% were female and had positive rheumatoid factor and 83% had radiological erosions. Eighty eight percent were in doses of 15 mg MTX, 4.9% with 10 mg and 25 mg at the beginning of LF treatment. Twenty four percent suffered from adverse events and 33% left the medication by 6 months. Among adverse events, 6 patients had diarrhea, 5 increased hepatic enzymes, 3 alopecia, 3 weight loss, and 2 had anemia and leucopenia. Eight patients stopped the medication in 6 months, but only 5 did because of adverse events. There was not significant statistical difference in adverse events between patients with different dose or routes of administration of MTX.

CONCLUSIONS

The presence of adverse events in MTX and LF combined treatment was low and it developed during the first 6 months of treatment in our patients. The MTX route of administration and doses did not influence on the toxicity of the combined treatment with LF. The combined therapy seems to be a safe treatment option in RA patients.