Can tofacitinib be used in a child ≥2 years with active polyarticular juvenile idiopathic arthritis refractory to conventional DMARDs (e.g., methotrexate), and what is the appropriate weight‑based dosing and monitoring?

Tofacitinib in Juvenile Rheumatoid Arthritis

Yes, tofacitinib can be used in children ≥2 years with active polyarticular juvenile idiopathic arthritis refractory to conventional DMARDs, with weight-based dosing of 5 mg twice daily (or equivalent weight-based doses for younger/smaller children), and it represents a recommended alternative when biologic DMARDs are unavailable or unaffordable. 1

Clinical Context and Positioning

The 2025 Pan-American League of Associations for Rheumatology (PANLAR) guidelines explicitly recommend Janus kinase inhibitors (tofacitinib and baricitinib) as potential treatment options for polyarticular JIA, particularly considering economic constraints where biologic DMARDs might not be readily available. 1 This represents a significant evolution from the 2019 American College of Rheumatology guidelines, which did not include JAK inhibitors in their recommendations. 1

The PANLAR guidelines specifically state that for patients with moderate activity (JADAS-27 ≥3.9–≤8.5) and poor prognostic factors or high disease activity (JADAS-27 >8.5), combination therapy with methotrexate and a biologic DMARD is preferred, but JAK inhibitors are recommended as alternatives when biologics are not accessible. 1

Evidence Base for Efficacy

The pivotal phase 3 randomized controlled trial demonstrated that tofacitinib significantly reduced JIA flare rates compared to placebo (29% vs 53%; hazard ratio 0.46,95% CI 0.27-0.79; p=0.0031) in patients with polyarticular course JIA. 2 This trial enrolled 225 patients aged 2 to <18 years with polyarticular course JIA (including extended oligoarthritis, RF-positive or RF-negative polyarthritis, or systemic JIA without active systemic features). 2

Long-term extension data through 48 months showed sustained efficacy with JIA-ACR70 response rates of 60.0% at month 1 that generally improved over time, and inactive disease achieved in 46.8% of patients at month 48. 3 Real-world data from Bangladesh demonstrated significant improvement in JADAS-27 scores, with 70.4% of patients achieving inactive disease at 24 weeks from a baseline of 100% high disease activity. 4

Weight-Based Dosing Regimen

The approved dosing is weight-based and age-stratified: 2, 5

• Children ≥2 to <6 years: Approximately 3.0 mg twice daily (adjusted based on pharmacokinetic data) 5
• Children 6 to <12 years: 2.5 mg twice daily 5
• Adolescents 12 to <18 years: 5 mg twice daily 5

The pharmacokinetic study established that these weight-based doses achieve similar drug exposure (AUCtau) across age groups: 156.6 ng•h/mL in adolescents, 118.8 ng•h/mL in 6-12 year olds, and 142.5 ng•h/mL in 2-6 year olds. 5 Tofacitinib is available as tablets or oral solution (grape flavor) with confirmed taste acceptability in young children. 5

Safety Profile and Monitoring

In the phase 3 trial, adverse events occurred in 77% of tofacitinib-treated patients during the withdrawal phase, with serious adverse events in only 1%. 2 Throughout the entire exposure period, 48% of patients had infections or infestations, with 10 patients developing serious infections and 3 developing herpes zoster in the long-term extension study. 3 Two patients newly developed uveitis during long-term treatment. 3

Common adverse events included: 4, 3

• Headache and vomiting (transient, improved by 6 weeks) 4
• Elevation of alanine aminotransferase (transient) 4
• Mild anemia (transient) 4
• Infections (most common overall adverse event) 3, 2

Required monitoring should include: 3, 2

• Complete blood count with differential at baseline and regularly during treatment
• Liver function tests at baseline, 6 weeks, and periodically thereafter
• Screening for latent tuberculosis before initiation
• Monitoring for signs of infection, particularly herpes zoster
• Ophthalmologic screening for uveitis development

Treatment Algorithm

For children ≥2 years with polyarticular JIA refractory to methotrexate:

1. First-line after methotrexate failure: Combination therapy with methotrexate plus a biologic DMARD (preferably anti-TNFα agent such as etanercept, adalimumab, or infliximab) is recommended for moderate activity with poor prognostic factors or high disease activity. 1

2. When biologics are unavailable, unaffordable, or contraindicated: Tofacitinib (or baricitinib) is recommended as an alternative, particularly relevant in resource-limited settings. 1

3. Combination with methotrexate: In the pivotal trial, 65% of patients received concomitant methotrexate, suggesting combination therapy is appropriate though not mandatory. 2

4. Assessment of response: Use JADAS-27 to monitor disease activity, with treatment escalation considered if no significant decrease after 3 months. 1

Critical Considerations

Tofacitinib should be considered particularly appropriate when: 1, 6

• Biologic DMARDs are not accessible due to cost or availability
• Patients or families prefer oral therapy over injections or infusions
• Patients have failed or are intolerant to conventional DMARDs including methotrexate
• Systemic features are present (case reports show efficacy in refractory systemic JIA) 6

Important caveats: 3, 2

• No deaths occurred in clinical trials, but long-term cardiovascular and malignancy risks seen in adult rheumatoid arthritis populations require ongoing surveillance
• Herpes zoster risk necessitates consideration of vaccination before treatment initiation where appropriate
• The medication was well-tolerated with minimal discontinuations due to adverse events in pediatric trials