Search for predictors of methotrexate toxicity in rheumatoid arthritis

Aim. To determine prognostic markers of methotrexate (MT) toxicity in rheumatoid arthritis (RA).

Materials and methods. The study included 294 patients with RA who were prescribed MT at a dose of 10 to 25 mg per week for the first time as basic anti-inflammatory therapy (BPVT). The following adverse events (AEs) were recorded: hepatotoxicity, toxicity from the gastrointestinal tract, blood system. Qualitative parameters were considered as possible predictors of MT intolerance: gender, obesity, smoking, systemic manifestations, as well as rheumatoid factor (RF), antibodies to cyclic citrullinated peptide (ACCP), intake of glucocorticosteroids (GCS), form of administration of MT; and quantitative: age of RA onset, baseline disease activity according to DAS28 (Disease Activity Score 28) and HAQ (Health Assessment Questionnaire), MT dose. Statistical processing was performed by one-factor methods using Pearson’s χ2 test with Yates correction, Fisher’s exact two-tailed test, Mann–Whitney U-test, and Student’s t-test. Multivariate analysis was carried out by binary logistic regression.

Results. In a univariate analysis, significant results were obtained for hepatotoxicity: a direct correlation with the use of corticosteroids at the onset (odds ratio (OR) 2.0; 95 % confidence interval (CI) 1.1–3.8, p = 0.03), inversely correlated with MT tablet intake (OR 0.5, 95 % CI 0.2–0.95, p = 0.03). According to the results of multivariate analysis, hepatotoxicity was recorded more often when taking GCS in the debut 2.01 times (95 % CI 1.02–3.96, p = 0.043), and in the presence of ACCP – 3.16 times (95 % CI 1.06–9.45, p = 0.039); and less frequently when taking tableted MT by 2.62 times (95 % CI 0.17–0.84, p = 0.017). Gastrointestinal toxicity tends to be associated with a younger age of RA onset (p = 0.06) and greater RA HAQ activity at onset (p = 0.07).

Conclusions. Hepatotoxicity is more expected in patients seropositive for ACCP and GCS treatment in the onset of RA, but is less common when taking MT tablets. AEs from the gastrointestinal tract are associated with a younger age of onset of the disease and a greater degree of activity according to the HAQ index.

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