Tofacitinib dosing regimen established for pediatric testing
medwireNews: Phase I study results suggest that the Janus kinase inhibitor tofacitinib is well tolerated in children with active polyarticular juvenile idiopathic arthritis (JIA), and that dosing based on bodyweight is appropriate.
Nicolino Ruperto (Istituto Giannina Gaslini, Genoa, Italy) and co-investigators divided 26 participants into three age categories (2–5, 6 –11, and 12–17 years). Children in the youngest age category weighing less than 30 kg, and those in the two older age categories weighing less than 40 kg, were given a grape flavored solution of oral tofacitinib 1 mg/mL twice daily for 5 days.
Children weighing more than these cutoff values were given tofacitinib 5 mg tablets, unless they preferred to receive the oral suspension. The median tofacitinib doses were 3.0 mg, 2.5 mg, and 5.0 mg twice daily in the youngest, middle, and oldest age category, respectively.
Following an interim pharmacokinetic analysis of the first 14 patients in the study, who were treated using doses scaled from established adult regimens, the dosing scheme was amended, which gave rise to the higher median dose of tofacitinib in the youngest versus the middle age category, explain the study authors.
The maximum plasma drug concentration observed during the dosing interval was 66.2 ng/mL for participants in the youngest age group, 41.7 ng/mL for patients in the middle category, and 47.0 ng/mL for those in the oldest age category. The median time taken to reach the maximum drug concentration was comparable across the three groups, at 0.5, 1.0, and 0.8 hours, respectively.
“[T]hese data support the use of a body weight-based dosing regimen in children with polyarticular course JIA,” say Ruperto and colleagues.
They report in Pediatric Rheumatology that tofacitinib was well tolerated, with no serious adverse events or deaths occurring during the study, and no patient discontinued treatment. Furthermore, the taste of the oral solution was considered “acceptable.” A total of 61.1% of participants said that they liked the taste “a little” or “very much” on the first day of treatment, and 50.0% said the same at day 5.
The researchers acknowledge, however, that “the small number of patients enrolled and the short duration of exposure to tofacitinib” allowed only short-term tolerability to be assessed, and that it was not possible to determine the drug’s long-term safety and efficacy profiles in the patient population studied.
Nevertheless, the study “established dosing regimens […] for use in subsequent studies within the tofacitinib pediatric development program,” they write, noting that tofacitinib has now moved into phase III trials in pediatric patients with JIA.
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