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Impact of tofacitinib on growth in patients with juvenile idiopathic arthritis
Hermine I Brunner1, Mittermayer Santiago2, Beth Gottlieb3
1Division of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Insights
Tofacitinib treatment in juvenile idiopathic arthritis (JIA) patients showed normal or increased growth velocity, with catch-up growth during puberty. Biomarkers for growth hormone signaling remained stable, indicating no concerning effects on bone metabolism.
Area of Science:
- Pediatric Rheumatology
- Pharmacology
- Endocrinology
Background:
- Juvenile idiopathic arthritis (JIA) can impact growth and bone metabolism.
- Janus kinase (JAK) inhibitors, like tofacitinib, are used to treat JIA.
- Long-term effects of JAK inhibitors on growth require evaluation.
Purpose of the Study:
- To assess the impact of tofacitinib on growth in patients with JIA.
- To evaluate changes in growth hormone (GH) function and bone metabolism biomarkers during tofacitinib treatment.
Main Methods:
- Post hoc analysis of 225 JIA patients receiving long-term tofacitinib.
- Calculation of height velocities and height Z-scores.
- Measurement of serum biomarkers (IGF-1, IGFBP-3, osteocalcin) in a subset of patients.
Main Results:
- Patients exhibited normal or increased height velocities relative to age-matched references.
- Height Z-scores remained stable, with catch-up growth observed in pubertal patients with baseline deficits.
- No significant changes in overall IGF-1, IGFBP-3, or osteocalcin levels, except for an increase in IGF-1 in 6-12 year olds.
Conclusions:
- Tofacitinib treatment in JIA is associated with normal or enhanced growth velocity.
- Pubertal catch-up growth was observed, suggesting no detrimental effect on linear growth.
- Biomarkers of GH signaling and bone metabolism showed no concerning changes during long-term tofacitinib therapy.
Objectives:
Tofacitinib is a Janus kinase inhibitor studied in different categories of juvenile idiopathic arthritis (JIA). This post hoc analysis evaluated the impact of tofacitinib on the growth of patients with JIA and on biomarkers of growth hormone (GH) function and bone metabolism.
Methods:
The analysis included 225 patients, primarily with polyarticular-course JIA, receiving long-term tofacitinib (median [IQR] follow-up 3.6 [1.9-4.6] years). Height velocities (cm/y) and height Z-scores (based on age- and sex-matched reference data) were calculated. Biomarkers were measured in serum from 137 patients with JIA completing 18 weeks of open-label treatment with tofacitinib.
Results:
This population of patients with JIA had a baseline height distribution similar to the general population. During treatment with tofacitinib, patients experienced height velocities that appeared greater (patients ≤12 years) or as expected (patients >12 years) relative to the reference for their ages. Height Z-scores were largely stable during treatment with tofacitinib. In patients in puberty and a height Z-score less than --1.0 at baseline, an increase in height Z-score (P < .05) was detected after 24 months of treatment. Tofacitinib treatment did not impact levels of insulin-like growth factor (IGF)-1, IGF binding protein 3 and osteocalcin in the overall population, but in patients aged 6 to 12 years, IGF-1 levels increased with tofacitinib from baseline to 18 weeks.
Conclusions:
This post hoc analysis of patients with JIA indicated normal or higher than expected growth velocity during long-term treatment, with tofacitinib with catch-up growth during puberty and, overall, no concerning changes in biomarkers of GH signalling.
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