Tofacitinib Dosing for Juvenile Idiopathic Arthritis
Tofacitinib should be dosed based on body weight in children with JIA: patients weighing ≥40 kg receive 5 mg twice daily (or 11 mg extended-release once daily), while those weighing 10 to <40 kg receive weight-based doses of approximately 5 mg/m² body surface area twice daily, administered as oral tablets or solution. 1, 2
Weight-Based Dosing Algorithm
The FDA-approved dosing regimen for JIA follows a structured weight-based approach established through pharmacokinetic studies:
- Patients ≥40 kg: 5 mg twice daily (standard tablet) or 11 mg once daily (extended-release formulation) 1, 2
- Patients 10 to <40 kg: Weight-based dosing using oral solution or tablets, targeting approximately 5 mg/m² BSA twice daily 2
- Patients 2 to <10 kg: Lower weight-based doses using oral solution 2
The pivotal phase 3 trial demonstrated that these weight-based doses achieved therapeutic drug exposure comparable to the adult 5 mg twice daily regimen, with geometric mean AUC values ranging from 118.8 to 156.6 ng•h/mL across age cohorts 2.
Clinical Efficacy Data
Tofacitinib demonstrated robust efficacy in polyarticular course JIA:
- Flare prevention: Only 29% of patients on tofacitinib experienced disease flare by week 44 compared to 53% on placebo (hazard ratio 0.46, p=0.0031) 1
- Response rates: JIA-ACR70 response achieved in 60% of patients by month 1, with JIA-ACR90 response in 33.6%, and these rates generally improved over time 3
- Disease remission: Inactive disease (JADAS27 ≤1.0) was achieved in 28.8% of patients at month 1 and increased to 46.8% by month 48 3
- Sustained benefit: Mean JADAS27 scores improved from 22.0 at baseline to 2.8 at month 48 3
Mandatory Laboratory Monitoring
CBC and liver function tests must be monitored within the first 1-2 months of starting tofacitinib and every 3-4 months thereafter. 4
Lipid levels should be checked 1-2 months after treatment initiation, as per FDA package insert. 4
Critical Dose Modification Thresholds
Tofacitinib must be discontinued immediately if any of the following occur: 4
- Hemoglobin <8 g/dL or decreases >2 g/dL
- Severe neutropenia (<500/mm³)
- Severe lymphopenia (<500/mm³)
These are strong recommendations based on FDA package insert safety parameters and are non-negotiable stopping criteria 4.
Dose Adjustments for Organ Dysfunction
In patients with moderate to severe renal impairment (CrCl <60 mL/min), reduce tofacitinib to 5 mg once daily. 4
In patients with severe hepatic disease (Child-Pugh C), tofacitinib should not be used. 4
For moderate hepatic impairment (Child-Pugh B), dose reduction is also recommended 4.
Drug Interactions Requiring Dose Modification
When co-administered with strong CYP3A4 inhibitors (e.g., ketoconazole), reduce tofacitinib dose to 5 mg once daily. 4
This is critical because strong CYP3A4 inhibitors significantly increase tofacitinib exposure, while CYP3A4 inducers (like rifampin used in TB treatment) decrease exposure and may require dose increases 4.
Concomitant Methotrexate Use
Tofacitinib can be used as monotherapy or in combination with methotrexate, with 65% of patients in the pivotal trial receiving concomitant methotrexate 1. The combination appears safe and may enhance efficacy, though tofacitinib monotherapy is also effective 1.
Pre-Treatment Screening Requirements
TB screening is conditionally recommended prior to starting tofacitinib, as it is classified as a biologic DMARD-equivalent therapy. 4
While the guidelines note this is conditional due to potential delays in urgent situations (e.g., systemic JIA with macrophage activation syndrome), TB screening should be performed in non-emergent cases 4.
Safety Profile in Long-Term Use
In the long-term extension study with median exposure of 41.6 months, 89.3% of patients experienced adverse events, but only 15.1% had serious adverse events 3. Key safety findings include:
- Infections: 48% of patients had infections or infestations during the entire exposure period 1
- Serious infections: Occurred in 10 patients, with 3 cases of herpes zoster 3
- Uveitis: Two patients newly developed uveitis during treatment 3
- No deaths were reported in the pivotal trial 1
The safety profile was consistent with adult rheumatoid arthritis data, with no unexpected pediatric-specific concerns 3.
Formulation and Administration
Tofacitinib is available as tablets for patients who can swallow pills or as a grape-flavored oral solution for younger children, with confirmed taste acceptability in children as young as 2 years 2. The oral solution allows precise weight-based dosing in younger patients 2.