What is the recommended treatment approach for juvenile idiopathic arthritis (JIA) in children using methotrexate (disease-modifying antirheumatic drug, DMARD)?

Methotrexate Treatment for Juvenile Idiopathic Arthritis in Children

Methotrexate is the recommended first-line disease-modifying antirheumatic drug (DMARD) for children with juvenile idiopathic arthritis (JIA), with a recommended dosage of 10-15 mg/m² body surface area per week. 1

Initial Treatment Approach

First-line Therapy

• Methotrexate is strongly recommended over NSAID monotherapy 1
• Methotrexate monotherapy is conditionally recommended over triple DMARD therapy 1
• For polyarticular JIA, methotrexate is the cornerstone DMARD due to its proven efficacy in inducing remission in 60-70% of children 1

Dosing and Administration

• Recommended dosage: 10-15 mg/m² body surface area per week 1
• Doses above 15 mg/m² BSA per week are not recommended as they show no additional therapeutic benefit 1
• Subcutaneous administration is conditionally recommended over oral administration 1
  • Subcutaneous route provides more consistent bioavailability, particularly important in younger patients who may have lower acceptance or intolerance to oral doses 1

Adjunctive Therapy

• NSAIDs (particularly naproxen) are recommended as adjunctive therapy for pain and inflammation 1
• Intraarticular glucocorticoid injections can be used as adjunct therapy 1
  • Triamcinolone hexacetonide is strongly recommended over triamcinolone acetonide for intraarticular injections 1
• A limited course of oral glucocorticoids (<3 months) during initiation or escalation of therapy is conditionally recommended for patients with moderate/high disease activity 1

Disease Monitoring and Treatment Escalation

Monitoring Response

• An adequate trial of methotrexate is considered to be 3 months 1
• If no or minimal response is observed after 6-8 weeks, changing or adding therapy may be appropriate 1

For Inadequate Response

• For patients with moderate/high disease activity on DMARD monotherapy:
  • Adding a biologic (TNF inhibitor, abatacept, or tocilizumab) to methotrexate is conditionally recommended over changing to a second DMARD 1
  • Adding a biologic is conditionally recommended over changing to triple DMARD therapy 1

For Patients Achieving Remission

• Continue methotrexate for at least 12 months after achieving remission 1
• Reported flare rates within 12 months of methotrexate withdrawal range from 30-50% 1

Managing Adverse Effects

Approximately 50% of children develop some form of adverse effect with methotrexate therapy 2. Common adverse effects include:

• Gastrointestinal symptoms (35.6%) 2
• Behavioral problems (35.6%) 2
• Elevated liver enzymes 2

Risk Factors for Adverse Effects

• Age older than 6 years at the beginning of therapy increases the risk of developing adverse effects 2
• Dose, administration route, or JIA classification were not associated with increased adverse effects 2

Managing Adverse Effects

• Modification of dosage or route of administration resolves adverse effects in approximately 55% of cases 2
• Folic acid supplementation may help reduce certain adverse effects
• In severe cases, treatment interruption may be necessary (occurs in about 35% of children) 2

Special Considerations

Combination Therapy with Biologics

• For patients receiving treatment with methotrexate, combination therapy with a biologic (etanercept, adalimumab, golimumab, abatacept, or tocilizumab) is conditionally recommended over biologic monotherapy for those with inadequate response 1
• Combination therapy with methotrexate is strongly recommended when using infliximab 1

Physical and Occupational Therapy

• Physical therapy and/or occupational therapy is conditionally recommended for children with JIA who have or are at risk of functional limitations 1

Important Caveats

• Early initiation of DMARD therapy is crucial for optimal disease outcomes 1
• Shared decision-making between physician, parents, and patient is recommended when initiating or escalating treatment 1
• Initial biologic therapy may be appropriate for some patients with risk factors and involvement of high-risk joints (e.g., cervical spine, wrist, or hip), high disease activity, or those at high risk of disabling joint damage 1
• Regular monitoring for adverse effects is essential, with particular attention to liver function tests

By following this evidence-based approach to methotrexate therapy in JIA, clinicians can optimize disease control while minimizing adverse effects, ultimately improving long-term outcomes and quality of life for affected children.