Tofacitinib Dosing for Down Syndrome Associated Arthritis in a 13-Year-Old
The recommended starting dose of tofacitinib for a 13-year-old patient weighing 29 kg with Down syndrome associated arthritis is 5 mg once daily, with dose adjustment based on renal function and monitoring parameters. 1
Dosing Considerations
Weight-Based Dosing
- For this 13-year-old patient weighing 29 kg, the standard adult dose must be adjusted
- The low body weight (29 kg) necessitates dose reduction from the standard adult dose of 5 mg twice daily 2
- Starting with 5 mg once daily is appropriate given the patient's weight and age
Special Population Considerations
- Down syndrome patients may have increased risk of infections and comorbidities
- Patients with renal impairment require dose adjustment to 5 mg once daily 1
- Hepatic function should be assessed before determining final dosing 2
Pre-Treatment Assessment
Required Laboratory Testing
- Complete blood count with differential
- Liver function tests
- Renal function tests
- Lipid profile
- Tuberculosis screening (IGRA or TST plus chest X-ray)
- Hepatitis B and C screening 1
Contraindications to Check
- Do not initiate if:
- Lymphocyte count <500 cells/mm³
- Absolute neutrophil count <1000 cells/mm³
- Hemoglobin <9 g/dL
- Severe hepatic impairment 1
Monitoring Requirements
Initial Monitoring (First 1-3 Months)
- Complete blood count at 1 month and 3 months
- Liver function tests at 1 month and 3 months
- Renal function at 1 month and 3 months
- Lipid levels at 3 months 2
Ongoing Monitoring
- Regular monitoring every 3 months for:
- Complete blood count with differential
- Liver function tests
- Renal function 2
- Annual lipid profile 1
- Monitor for signs of infection, particularly herpes zoster 1
Dose Adjustment Criteria
When to Reduce Dose
- If moderate hepatic impairment develops (Child Pugh B) 2
- If moderate to severe renal impairment develops 1
- If patient is taking CYP3A4 inhibitors 1
When to Discontinue
- Hemoglobin <8 g/dL or decreases >2 g/dL
- Absolute neutrophil count <500/mm³
- Absolute lymphocyte count <500/mm³
- Serious infection 1
Safety Considerations for Pediatric Patients
- Increased risk of infections, particularly herpes zoster, compared to other DMARDs 3
- Monitor for signs of serious and opportunistic infections 1
- Avoid live vaccines during treatment 1
- Consider administering recombinant zoster vaccine before initiating therapy if appropriate 1
Clinical Efficacy Expectations
- Improvement in joint symptoms may be seen as early as 2 weeks after initiation 4
- Assess response using validated disease activity measures at 3 months 2
- Target >50% improvement in disease activity by 3 months 2
- If inadequate response at 3 months, consider dose adjustment or alternative therapy 2
Tofacitinib has demonstrated efficacy in various forms of inflammatory arthritis 5, 6, though specific data in Down syndrome associated arthritis is limited. The medication's oral administration may be advantageous for pediatric patients compared to injectable biologics, but careful monitoring is essential due to the potential for serious adverse events.