Tofacitinib Dosing for Down Syndrome Associated Arthritis and JIA
For pediatric patients with juvenile idiopathic arthritis (JIA) including Down syndrome associated arthritis, the recommended weight-based dosing of tofacitinib is 3.0 mg twice daily for children 2 to <6 years, 2.5 mg twice daily for children 6 to <12 years, and 5.0 mg twice daily for children 12 to <18 years. 1
Dosing Guidelines
The dosing of tofacitinib for pediatric patients with JIA follows a weight-based approach:
- Ages 2 to <6 years: 3.0 mg twice daily
- Ages 6 to <12 years: 2.5 mg twice daily
- Ages 12 to <18 years: 5.0 mg twice daily
This weight-based dosing strategy is supported by clinical evidence showing efficacy in polyarticular course JIA, which would include Down syndrome associated arthritis 2.
Efficacy in JIA
Tofacitinib has demonstrated significant efficacy in pediatric patients with polyarticular course JIA:
- A phase 3 randomized trial showed that tofacitinib significantly reduced JIA flare rates compared to placebo (29% vs 53%) 2
- Significant improvement in Juvenile Arthritis Disease Activity Score (JADAS) has been observed across multiple JIA subtypes 3
- 70.4% of patients with high disease activity at baseline achieved inactive disease status by 24 weeks of treatment 3
Dose Adjustments for Special Populations
Dose adjustments are necessary in certain clinical situations:
- Severe renal impairment (CrCl <30 mL/min): Reduce dose to 5 mg once daily 1
- Moderate hepatic impairment: Reduce dose to 5 mg once daily 1
- Severe hepatic impairment (Child-Pugh C): Not recommended 1
- With CYP3A4 inhibitors or medications inhibiting both CYP3A4 and CYP2C19: Reduce dose to 5 mg once daily 1
Monitoring Recommendations
Regular monitoring is essential when using tofacitinib in pediatric patients:
- Baseline assessments: Complete blood count, liver function tests, renal function tests, and TB screening
- Ongoing monitoring:
- Complete blood count: Every 3 months
- Liver function tests: Monthly for first 3 months, then every 3 months
- Renal function tests: Every 3 months 1
Safety Considerations
Discontinue tofacitinib if:
- Lymphocyte count <500 cells/mm³
- Absolute neutrophil count <500 cells/mm³
- Hemoglobin decreases by ≥2 g/dL or is <8.0 g/dL 1
Concomitant Medications
- Tofacitinib can be used as monotherapy or in combination with methotrexate 2
- In clinical trials, 65% of patients received concomitant methotrexate 2
- Avoid combination with biologic DMARDs or potent immunosuppressants like cyclosporine or tacrolimus due to increased risk of immunosuppression 4
Practical Considerations
- Tofacitinib offers an oral alternative to injectable biologics, which may be preferred by children and adolescents 2
- The medication has shown efficacy in refractory cases of JIA, including various subtypes 3
- Monitor for infections, particularly herpes zoster, which occurs at higher rates with tofacitinib compared to other treatments 4