PICO research questions and recommendations | Grade of evidence | Supporting references |
---|---|---|
Research question 1: Efficacy and safety of methotrexate in juvenile idiopathic arthritis | ||
1. MTX is recommended as the first-line treatment in oligoarthritis that persists despite nonsteroidal anti-inflammatory drugs (NSAIDs) and intraarticular steroid (IAS) therapy, and in polyarticular disease | 1A | |
MTX is also recommended in systemic arthritis with predominant joint inflammation, without active systemic features | 4C | |
2. Clinical and laboratory monitoring of MTX toxicity is recommended every 4-8 weeks initially, and then every 12-16 weeks, unless risk factors are present | 4C | [1, 4, 12, 21, 26,27,28,29,30,31,32,33,34,35,36,38,38, 40,41,42] |
Research question 2: Dosages of methotrexate in juvenile idiopathic arthritis | ||
3. A dose of 10-15 mg/m2/week is recommended. | 5D | |
Further increases in MTX dosage have not been associated with additional therapeutic benefit | 1A | |
Research question 3: Route of administration of methotrexate in juvenile idiopathic arthritis | ||
4. MTX may be given orally or subcutaneously once a week. If high doses (15 mg/m2/week) are requested, the subcutaneous route is preferable due to increased bioavailability | 4C | |
Research question 4: Tapering and discontinuation of methotrexate in juvenile idiopathic arthritis | ||
5. MTX could be discontinued after 6 months of stable remission | 1A | |
Research question 5: Folic acid supplementation for the prevention of methotrexate toxicity in patients with juvenile idiopathic arthritis | ||
6. Folic or folinic acid supplementation is recommended to prevent MTX side effects. | 1A | |
The advised dose is approximately one third of the MTX dose, at least 24 hours after the weekly dose of MTX for folinic acid; for folic acid 1 mg/day skipping the day when MTX is administered | 4C | |
Research question 6: Efficacy of methotrexate in uveitis associated with juvenile idiopathic arthritis | ||
7. MTX is recommended for the treatment of JIA-related uveitis refractory to topical treatment | 4C | |
Research question 7: Add-on therapy with biologic drugs in juvenile idiopathic arthritis not responding to methotrexate | ||
8. The combination of MTX with a TNF-α inhibitor is recommended in patients who had an inadequate clinical response to MTX alone | 3B | |
Combination therapy is safe and may reduce the development of anti-drug antibodies | 2B | |
Research question 8: Molecular elements and genetic markers of response to methotrexate in juvenile idiopathic arthritis – Biomarkers | ||
9. No recommendation is made regarding the use of biomarkers in current clinical practice | ||
Research question 9: Use of vaccination in patients with juvenile idiopathic arthritis treated with methotrexate | ||
10. Vaccination with non-live vaccines is not contraindicated during MTX treatment | 2B | [101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119] |
No recommendation can be formulated for live-attenuated vaccines, but the available data for measles, mumps, rubella (MMR) booster indicate that it is safe and adequately immunogenic |