Children as young as two years old in Europe now have access to an oral JAK inhibitor option for polyarticular juvenile idiopathic arthritis (pJIA), after the European Commission approved upadacitinib (Rinvoq) for the indication in patients who have responded inadequately to, or are intolerant of, one or more disease-modifying anti-rheumatic drugs (DMARDs).
The approval covers patients aged two years and older with polyarticular rheumatoid factor positive, rheumatoid factor negative, or extended oligoarticular subtypes of pJIA. AbbVie (NYSE: ABBV) said the drug may be used as monotherapy or in combination with methotrexate, and is available as both a 15 mg prolonged-release tablet and a weight-based 1 mg/mL oral solution to accommodate younger and smaller patients.
The decision was supported by the SELECT-YOUTH study, a single-arm, open-label, global Phase I trial evaluating the pharmacokinetics, efficacy, safety, and tolerability of upadacitinib in 122 patients aged 2 to under 18 years with polyarticular course juvenile idiopathic arthritis. At week 12, 66.4% of patients achieved an ACR Pedi 70 response, a composite measure of substantial improvement across pediatric JIA disease-activity measures, rising to 79.5% at week 48 using nonresponder imputation. Remission, defined as a JADAS27-CRP score of 1 or below, was achieved in 23.0% of patients at week 12 and 43.4% at week 48.
AbbVie said no new safety signals were identified in the pediatric population. Treatment-emergent adverse events occurred at a rate of 499.6 events per 100 patient-years, while serious adverse events occurred at 10.2 events per 100 patient-years. The company said the overall safety profile was consistent with the known profile of upadacitinib in adults.
Upadacitinib is a selective and reversible JAK inhibitor that preferentially inhibits signaling through JAK1 or JAK1/3, with functional selectivity over cytokine receptors signaling via JAK2 pairs. The EU decision follows FDA approval of upadacitinib for active pJIA and pediatric psoriatic arthritis in patients aged two years and older in April 2024. The pediatric program uses weight-based exposure matching to bridge from the drug's established adult clinical experience, alongside direct efficacy and safety data from SELECT-YOUTH.