How methotrexate efficacy is associated with dose and route of administration

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How methotrexate efficacy is associated with dose and route of administration

Methotrexate (MTX) has been long used for treating various problems like cancer of skin, breast, neck and head or lung. It has also been efficacious for curbing severe psoriasis and rheumatoid arthritis. But, there is insufficient data available for the significance of methotrexate (MTX) dose and route of administration on its efficacy and adverse events in children with juvenile idiopathic arthritis (JIA). The clinical practise implemented here in this study is based on the treat-to-target approach in order to support the concept that better therapeutic effect achieved with an optimal dose of parenteral MTX. In turn, MTX is related to clinically acceptable adverse effects as distinguished from those reported for oral treatment.

The patients involved had confirmed JIA and were younger than 18 years. The eligible patients were likely to be evaluated every 3 months for 1 year using standardized instruments for treatment response (Juvenile Arthritis Disease Activity Score (JADAS) 71, Clinically Inactive Disease (CID), American College of Rheumatology Pediatric (ACRPedi) response) and adverse events (Methotrexate Intolerance Severity Score (MISS), laboratory monitoring). At least, ACRPedi 70 response has to be obtained by MTX responders. For MTX intolerance, MISS ≥ 6 is needed.

The subcutaneous injection was initiated in 45 out of 55 patients (81.8 %) MTX. At the beginning, median weekly dose was 14.4 mg/m2 in parenteral and 11.7 mg/m2 in oral administration. At month 6, ACRpedi70 and CID levels varied effectively- 50.9 % and 30.9 % of patients with the MTX therapy and in 70.9 % and 56.4 % after 12 months of treatment. The MTX intolerance at 6 and 12 months was recorded as 25.5 % and 30.6 %, respectively. Proper management of intolerance inculcated change in the dose and/or route of administration, education and councelling. MTX withdrawal was observed due to adverse events in 5 patients (9 %) due to toxicity (n = 3) and intolerance (n = 2). No worth-noting predictive factors for either MTX therapeutic response or intolerance was revealed.

Thus, we cease to know that subcutaneous MTX weekly dose around 15 mg/m2 is associated not only with a high response rate within the first 12 months of treatment, but also with a relatively low rate of significant adverse effects that would terminate it. It allows early identification of MTX non-responders and addition of biologic therapy. Future studies are necessary to infer the sustainability of therapeutic effect and longer-term evolution of adverse events with the help of ongoing extension of the study. 

Pediatr Rheumatol Online J.
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