FRI0048 Side effects of methotrexate in therapy for rheumatoid arthritis ? five years prospective study
Authors: SK Stojanovic, AM Stankovic, JM Nedovic, BN Stamenkovic, AN Dimic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Methotexate (MTX) has one of the best efficacy/toxicity ratios. Toxic effects, rather than lack of response, were the major reason for discontinuing MTX. <h3>Objectives</h3> Our aim was to determine the frequency and spectrum of side effects in patients with rheumatoid arthritis (RA) receiving low doses of MTX and eventually to determine existence of risk factors for appearance of side effects. <h3>Methods</h3> During five years period, 70 patients with active RA were enrolled in a prospective study. They all fulfilled ARA criteria. There were 54 women and 16 man, between 27 and 76 years. The mean duration of disease was 9,76 ± 7,58 years. They were treated with low doses of MTX (5 ? 12,5 mg once a week; mean dose 7,5 mg once a week). The mean duration of MTX treatment was 2,82 ± 2,27 years. MTX was given to 27 (38,57%) patients without prior treatment with disease modifying antirheumatic drugs. Most of the patients were treated with NSAID and low doses of prednison, according to indications. Patients with any of the contraindications for MTX (renal, hepatic and pulmonary failure, malignant disease, alcoholism, haematological disorders and uncontrolled diabetes) were excluded from the study. Monitoring of the side effects included radiography of lungs at the beginning of the study and regularly control of complete blood account, urine analyses, liver and renal function. <h3>Results</h3> Adverse effects were found in 27 (38,57%) patients, which required withdrawal of the drug only in 7 (10%) patients. Other adverse effects were transitory and enabled continuation of therapy with dose reduction in 10 (14,28%) patients. The most frequent side effects were gastrointestinal intolerance, in 15 (21,43%) patients, required cessation of therapy in one patient. Four patients had elevated liver enzymes in more consecutive analyses, urging stopping in three cases. Haematological disorders were detected in six (8,57%) patients, with trombocitopenia in four and leucopoenia and pancitopenia in rest of two patients. Patient with pancitopenia and one with severe trombocitopenia stopped with therapy. Hypersensitive pneumonitis appeared in one patient, after three months of therapy, with complete resolution after cessation of therapy. One patient had mild herpes zoster infection, which required only transitory withdrawal of the drug. The adverse effects were seen mostly in the first year of the therapy? 18 (25,71%) cases. Also all withdrawals were done in the first year, with cumulative dose from 30 mg. to 340 mg. (average 204,29 mg.). The greatest number of side effects was a registry among the oldest group of patients (from 60 to 80 age) ? 16 (59,06%) patients. All three patients with control diabetes shoved some adverse effects. <h3>Conclusion</h3> Low dose of MTX is a relatively safe therapy, especially with careful patient selection. Special attention is required for older patients as for patients with diabetes and other risk factors for MTX toxicity. Regular monitoring for side effects is mandatory during the whole period of therapy.