Recommendations for the Use of Methotrexate in Juvenile Idiopathic Arthritis

Abstract

Juvenile idiopathic arthritis (JIA) is one of the most common rheumatic diseases in childhood. In a significant number of JIA cases the disease is resistant to therapy with NSAIDs, intra-articular corticosteroid injections, and physiotherapy, and methotrexate is used as a second-line agent. The efficacy of methotrexate therapy in children with JIA has been demonstrated in prospective controlled trials and this agent appears to have slightly superior efficacy compared with leflunomide. Data from randomized studies indicate a starting dose of 10-15 mg/m(2)/week orally. The dose of parenteral methotrexate can be increased to 15-20 mg/m(2)/week. Combination therapy with methotrexate and an NSAID is recommended. However, there are still no data on when to initiate methotrexate in JIA and how long children should be treated. The most common adverse effects are aversion to the drug and nausea. In the case of minor adverse effects the use of folic acid at a dosage of 1 mg/day is feasible. In JIA, daily folate supplementation has only been studied in one small heterogeneous cohort with a very short observation period and, at present, a general recommendation on daily folate supplementation cannot be made. In summary, methotrexate is seen by many pediatric rheumatologists as the first-choice, second-line drug; there is good evidence of its efficacy in JIA. However, in light of the recent introduction of biologic agents, the place of methotrexate in the treatment of JIA may have to be redefined in the coming years.

In Vitro Activity of Antifolate and Polymorphism in Dihydrofolate Reductase ofPlasmodium falciparumIsolates from the Kenyan Coast: Emergence of Parasites with Ile-164-Leu Mutation

“…In the present work, we have provided data on the activity of MTX against field isolates. MTX is active, with a median IC 50 (18,38). At this dose, MTX is safe and well tolerated and can yield MTX concentrations around 250 to 950 nM (15,17).…”

A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers

“…This dose can yield serum concentrations of >1000 μM, a concentration range associated with MTX life-threatening toxicity [11]. By contrast, a 1000-fold lower dose of MTX (LD-MTX) [0.1-0.4 mg/kg (7.5-30 mg per adult)] is used once weekly in the treatment of rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) in children (including infants <one year old) and psoriasis [12-14]. This use of LD-MTX is relatively safe and well tolerated, and children tolerate it better than adults [14].…”

“…By contrast, a 1000-fold lower dose of MTX (LD-MTX) [0.1-0.4 mg/kg (7.5-30 mg per adult)] is used once weekly in the treatment of rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) in children (including infants <one year old) and psoriasis [12-14]. This use of LD-MTX is relatively safe and well tolerated, and children tolerate it better than adults [14]. Pharmacokinetic data indicate that LD-MTX yields in vivo concentrations >250 nM, which can clear malaria parasites in vivo (MTX IC 99 of 200-400 nM) [15-17].…”

Pharmacotherapy of Juvenile Idiopathic Arthritis

“…Although evidence is limited for enhanced efficacy, some have advocated dose increases up to 25 mg/m 2 subcutaneously if necessary. 25 A randomized, controlled trial found that 30 mg/m 2 was no more effective than 15 mg/m 2 . 28 Methotrexate can be given orally, intramuscularly, or subcutaneously.…”