European Commission Approves AbbVie's RINVOQ (upadacitinib) for Polyarticular Juvenile Idiopathic Arthritis in Children Aged 2 and Older
核心洞察
The European Commission approved RINVOQ (upadacitinib) for active polyarticular juvenile idiopathic arthritis (搜索) in patients aged 2 years and older who responded inadequately to or are intolerant to one or more DMARDs.
The approval covers a 15 mg tablet and a new weight-based 1 mg/mL oral solution, and the drug may be used as monotherapy or with methotrexate.
The decision was supported by the single-arm, open-label Phase 1 SELECT-YOUTH study plus data from adults with rheumatoid arthritis (搜索), with efficacy seen as early as week 12 and improving through week 48.
The European Commission has approved RINVOQ (upadacitinib) for the treatment of active polyarticular juvenile idiopathic arthritis (搜索) (pJIA) in patients two years of age and older who have responded inadequately to, or who are intolerant to, one or more disease-modifying anti-rheumatic drugs (DMARDs). The approval covers a 15 mg tablet and a new weight-based 1 mg/mL oral solution, and the drug may be used as monotherapy or in combination with methotrexate.
The indication specifies polyarticular rheumatoid factor positive (RF+) or negative (RF-) and extended oligoarticular disease. With this decision, RINVOQ is approved in the European Union for 11 indications across immune-mediated, inflammatory diseases.
"The European Commission's approval of RINVOQ for pJIA expands the treatment options available to pediatric patients and their families, offering the potential for remission, improvements in pain and physical function," said Roopal Thakkar, M.D., executive vice president, research and development, chief scientific officer, AbbVie.
Disease Burden in Pediatric Rheumatology
Juvenile idiopathic arthritis (搜索) is the most common rheumatic disease of childhood and is estimated to impact approximately 126,000 children in Europe. pJIA is a subtype characterized by inflammation in five or more joints, including the small joints of the hands and feet and large joints such as the knees, hips and ankles, persisting for at least six weeks in children and adolescents.
The disease can be painful and debilitating and, if left untreated, may lead to joint damage. Ongoing disease activity is common, with persistent symptoms or flares affecting many patients into adulthood.
SELECT-YOUTH Study Design and Efficacy
The approval is supported by the SELECT-YOUTH study and data from adult patients with rheumatoid arthritis (搜索). SELECT-YOUTH (M15-340) is a single-arm, open-label, global Phase 1 study evaluating the pharmacokinetics, efficacy, safety and tolerability of upadacitinib in patients with polyarticular course juvenile idiopathic arthritis (搜索) (pcJIA) ages 2 to under 18 years.
The study consists of three parts. Part 1 was a seven-day multiple-dose pharmacokinetic evaluation, after which patients in Parts 2 and 3 received a low dose of upadacitinib equivalent to 15 mg, delivered as either a twice-daily oral solution or a once-daily extended-release tablet based on body weight and ability to swallow tablets. The trial is registered as NCT03725007.
RINVOQ demonstrated efficacy as early as week 12, with response rates improving through week 48. The efficacy observed in children with pJIA was generally consistent with responses in adult patients with rheumatoid arthritis (搜索).
Functional ability, measured by the Childhood Health Assessment Questionnaire (C-HAQ), improved with a mean change from baseline of -0.46 (n=115) at week 12 and -0.64 (n=108) at week 48. Pain scores improved with a mean change from baseline of -26.2 (n=116) at week 12 and -30.8 (n=109) at week 48. C-HAQ and pain data are reported as observed.
"The SELECT-YOUTH results underscore that clinical remission for children with pJIA is not a rare hope but a critical and achievable outcome that helps reduce the risk of permanent joint damage in some of our youngest, most vulnerable patients," said Prof. Dr. Gerd Horneff, head of the Department of General Pediatrics, Asklepios Clinic, Sankt Augustin, Germany. "The approval of RINVOQ in active pJIA provides a new oral systemic treatment option for patients suffering from this often-debilitating condition."
Safety Findings
No new safety risks were identified in the study. The rate of treatment-emergent adverse events was 499.6 events per 100 patient-years (E/100 PY). The rate of serious adverse events was 10.2 E/100 PY, and the rate of treatment-emergent adverse events leading to discontinuation of the study drug was 2.7 E/100 PY.
No cases of major cardiovascular or thrombotic events, malignancies or deaths were reported during the study period, and no negative impact on growth or development was observed. The overall safety profile in pediatric patients with pJIA treated with RINVOQ was consistent with the known safety profile of the drug.
Mechanism and Broader Development Program
RINVOQ was discovered and developed by AbbVie scientists and is a selective and reversible JAK inhibitor being studied in several immune-mediated inflammatory diseases. In human cellular assays, it preferentially inhibits signaling by JAK1 (搜索) or JAK1/3 with functional selectivity over cytokine receptors that signal via pairs of JAK2.
The drug is also approved in the European Union for adults and adolescents with atopic dermatitis, non-segmental vitiligo and alopecia areata, and for adults with radiographic axial spondyloarthritis, non-radiographic axial spondyloarthritis, psoriatic arthritis, rheumatoid arthritis (搜索), ulcerative colitis, Crohn's disease and giant cell arteritis.
Upadacitinib is being studied in Phase 3 clinical trials for hidradenitis suppurativa, Takayasu arteritis and systemic lupus erythematosus, and in pediatric studies for systemic juvenile idiopathic arthritis (搜索), atopic dermatitis, ulcerative colitis and Crohn's disease.
Labeling Considerations
The European Union label carries contraindications for patients hypersensitive to the active substance or excipients, patients with active tuberculosis or active serious infections, patients with severe hepatic impairment, and during pregnancy. RINVOQ should only be used if no suitable treatment alternatives are available in patients aged 65 years and older, patients with a history of atherosclerotic cardiovascular disease or other cardiovascular risk factors, and patients with malignancy risk factors.
Serious and sometimes fatal infections have been reported in patients receiving RINVOQ, most frequently pneumonia and cellulitis. Patients should be screened for tuberculosis before starting treatment, and live attenuated vaccines are not recommended during or immediately prior to therapy. Lymphoma and other malignancies have been reported with JAK inhibitors, including RINVOQ. The label also notes dose-dependent increases in lipid parameters, elevated hepatic transaminases, venous thromboembolism events, and retinal vein occlusion.
RINVOQ is available as 15 mg, 30 mg and 45 mg prolonged-release tablets and as a 1 mg/mL oral solution. The tablets and oral solution are not bioequivalent.