What is the treatment approach for a pediatric patient with Polyarticular Juvenile Rheumatoid Arthritis (JRA), also known as Polyarticular Giant Cell Arthritis (PGALs)?

Treatment of Polyarticular Juvenile Idiopathic Arthritis (Poly-JIA)

For pediatric patients with polyarticular JIA, initiate methotrexate as first-line DMARD therapy immediately alongside NSAIDs, using a treat-to-target approach with JADAS-27 monitoring every 3 months to achieve inactive disease and prevent irreversible joint damage. 1

Disease Definition and Risk Stratification

Polyarticular JIA encompasses arthritis in ≥5 joints cumulatively, including RF-positive and RF-negative polyarthritis, extended oligoarthritis, and undifferentiated arthritis with >4 joints involved. 1, 2 This broader clinical phenotype is characterized by prolonged periods of active disease that increase risk for joint damage, impaired quality of life, and worse functional outcomes. 1

Assess disease activity using JADAS-27 score at baseline and every 3 months:

• Low disease activity: JADAS-27 ≤2.5 with ≥1 active joint 1, 3
• Moderate/high disease activity: JADAS-27 >2.5 1, 3

Identify poor prognostic features that warrant more aggressive treatment: 3, 4

• Symmetric polyarticular involvement
• High-risk joint involvement (hip, wrist, cervical spine, ankle, temporomandibular joint)
• RF-positive or anti-CCP positive serology
• Elevated inflammatory markers (ESR, CRP)
• Presence of erosive disease or joint space narrowing on radiographs

Initial Treatment Strategy

First-Line Therapy for All Disease Activity Levels

Start methotrexate immediately as the preferred DMARD over other conventional DMARDs like leflunomide or sulfasalazine. 1, 3 The American College of Rheumatology strongly recommends DMARD therapy over NSAID monotherapy to prevent long-term joint damage. 1

Methotrexate dosing specifics:

• Use subcutaneous methotrexate over oral formulation for better bioavailability 1, 3
• Typical dosing range: 10-15 mg/m²/week (up to 20-25 mg/week) 5
• Add folic acid supplementation to reduce gastrointestinal and hepatic adverse effects 5

Adjunctive NSAIDs (naproxen, ibuprofen, or tolmetin) should be prescribed at anti-inflammatory doses for symptom control. 1, 2

Consider short-course oral glucocorticoids or intra-articular injections for rapid symptom control while awaiting DMARD effect:

• Use triamcinolone hexacetonide over triamcinolone acetonide for intra-articular injections due to longer duration of action 1, 3
• Limit systemic glucocorticoid use to minimize growth suppression and osteoporosis 1

Special Consideration for High-Risk Patients

For patients with multiple poor prognostic features, high-risk joint involvement, and very high disease activity, initial biologic therapy may be appropriate rather than waiting for methotrexate failure, though this remains an area of ongoing research. 1 However, the standard recommendation remains to start with methotrexate first. 1, 3

Treatment Escalation Algorithm

After 6-8 Weeks: Assess Initial Response

If no or minimal response after 6-8 weeks of methotrexate, consider changing or adding therapy rather than waiting the full 3 months. 1

After 3 Months: Formal Treatment Reassessment

An adequate trial of methotrexate is defined as 3 months at therapeutic doses. 1

For Patients with Persistent Moderate/High Disease Activity (JADAS-27 >2.5):

Add a biologic DMARD to methotrexate (combination therapy preferred over biologic monotherapy): 1, 3

First-line biologic options (all FDA-approved for poly-JIA):

• TNF inhibitors: Etanercept (age ≥2 years), adalimumab (age ≥4 years) 1, 6
• IL-6 receptor inhibitor: Tocilizumab (age ≥2 years) 1
• T-cell co-stimulation modulator: Abatacept (age ≥6 years) 1

The choice between these agents should consider patient age, route of administration preferences, and comorbidities, as comparative effectiveness data are limited. 1

For Patients with Persistent Low Disease Activity (JADAS-27 ≤2.5 but ≥1 active joint):

Escalate therapy even with only one active joint to achieve complete disease control. 1 Options include:

• Optimizing methotrexate dose (if not at maximum)
• Adding a biologic DMARD 1
• Targeted intra-articular glucocorticoid injections for persistently active joints 1, 3

After Biologic Failure

If inadequate response to first TNF inhibitor after 3 months:

• Switch to a different TNF inhibitor (etanercept, adalimumab, or infliximab) 1
• OR switch to a different mechanism: abatacept, tocilizumab, or rituximab 1

For resource-limited settings where biologics are unavailable, the Pan-American League of Associations for Rheumatology recommends considering JAK inhibitors (tofacitinib, baricitinib) as alternative treatment options. 1

Monitoring and Follow-Up

Reassess disease activity every 3 months using JADAS-27 to guide treatment adjustments in this tightly controlled, treat-to-target approach. 1

Monitor for treatment-related adverse effects:

• Methotrexate: Liver function tests, complete blood count (monitor for leukopenia, thrombocytopenia, pancytopenia), pulmonary symptoms (interstitial pneumonitis occurs in ~1% of patients) 5
• Biologics: Infection risk, injection site reactions, infusion reactions 6
• All patients: Screen for uveitis regularly, particularly in ANA-positive patients 2

Treatment Goals and Outcomes

Primary objective: Achieve inactive disease, defined by absence of active arthritis, normal inflammatory markers, and physician global assessment indicating no disease activity. 1, 4

Clinical remission on medication requires maintaining inactive disease for ≥6 months while on therapy. 4

The 2019 randomized study demonstrated that approximately 71% of treatment-naive JIA patients achieved inactive disease after 2 years using this treat-to-target approach, with 39% remaining drug-free. 1

Critical Pitfalls to Avoid

Do not delay DMARD initiation. Starting with NSAID monotherapy leads to prolonged active disease, increased joint damage, and worse long-term outcomes. 1, 2

Do not wait the full 3 months if there is no response at 6-8 weeks. Early treatment adjustment prevents irreversible joint damage. 1

Do not accept persistent low disease activity as adequate control. Even one active joint warrants treatment escalation to prevent long-term damage. 1

Do not use live vaccines in infants exposed to adalimumab in utero until adalimumab levels are undetectable (can persist up to 3 months after birth). 6

Recognize that quality of life may remain suboptimal despite achieving clinical remission. Up to 26% of patients with polyarticular JIA treated with biologics for 12 months report suboptimal health-related quality of life despite good disease control, necessitating holistic assessment beyond joint counts. 7

Regional Considerations

In Latin America and other resource-constrained settings, access to biologics remains limited due to economic barriers despite their inclusion in the WHO Model List of Essential Medicines for Children. 1 In these contexts, optimize conventional DMARD therapy and consider JAK inhibitors as alternatives when biologics are unavailable. 1