FDA Approves 2 Upadacitinib Formulations for Children with pJIA & PsA

Pediatric rheumatologists now have a new treatment option for children aged 2 years or older who have had an inadequate response to, or demonstrated intolerance to, one or more tumor necrosis factor (TNF) inhibitors. In June, the U.S. Food & Drug Administration (FDA) approved upadacitinib (Rinvoq), a Janus kinase inhibitor, for the treatment of children with active polyarticular juvenile idiopathic arthritis (pJIA) and active psoriatic arthritis (PsA).¹ The FDA also approved a new drug application for the use of 1 mg/mL of upadacitinib (Rinvoq LQ) in an oral solution for the same patient populations.^2,3

The recommended doses of upadacitinib in pediatric patients are weight-based. The doses for the oral solution are:

• 3 mg of upadacitinib twice daily for patients weighing 10 kg to <20 kg;
• 4 mg of upadacitinib twice daily for patients weighing 20 kg to <30 kg; and
• 6 mg of upadacitinib twice daily—or a 15 mg tablet once daily—for patients weighing >30 kg.

Other Indications

In August 2019, the FDA initially approved 15 mg of upadacitinib in extended-release tablets for the treatment of moderate to severe active rheumatoid arthritis (RA) for adults who have had an inadequate response to, or intolerance to, methotrexate.⁴ In December 2021, the FDA expanded the initial indication to include adults with active PsA who have had an inadequate response to, or intolerance to, one or more TNF inhibitors.⁵  

Upadacitinib is also FDA approved for the treatment of:

• Adults and children aged 12 years and older with refractory, moderate to severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, such as biologics, or when use of those therapies is inadvisable;
• Adults with moderate to severe active ulcerative colitis or Crohn’s disease who have had an inadequate response to, or intolerance to, one or more TNF inhibitors;
• Adults with active ankylosing spondylitis (AS) who have had an inadequate response to, or intolerance to, one or more TNF inhibitors; and
• Adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation who have had an inadequate response to, or intolerance to, TNF inhibitor therapy.⁶

The Research

This latest FDA approval of upadacitinib in pediatric patients is supported by exposure-matched extrapolation of the established efficacy of upadacitinib in patients with RA.⁷ The efficacy and safety of upadacitinib in patients with pJIA was assessed in a multi-center trial in children ages 2 to less than 18 years old (N=83) in an open-label, single-arm study (NCT03725007). At baseline, the study patients had different pJIA subtypes. All patients used weight-based doses of upadacitinib tablets for up to 156 weeks. The study permitted patients who were receiving a stable dose of methotrexate to enter the study, as well as changes to methotrexate dosing during the study. Efficacy was assessed through 48 weeks.

The study’s efficacy findings were largely consistent with responses in patients with RA. No serious adverse events or adverse events leading to drug discontinuation were reported during the study.⁸ Most adverse events were mild to moderate, consisting of COVID-19 infection, upper respiratory tract infection, nasopharyngitis, gastroenteritis, fever, abdominal pain and nausea. A high proportion of patients (84% and greater) in two age groups—2 to <6 years old and 6–10 years old—achieved a JIA ACR30, 50 and 70 response (i.e., a 30, 50 or 70% reduction in the signs and symptoms of JIA) at week 12.

Clinical Considerations

The upadacitinib oral solution is not substitutable with the upadacitinib extended-release tablets. Any changes between these formulations should be made by a qualified clinician.

Prior to treatment, clinicians should update the patient’s immunizations. Also consider evaluating the patient for active and latent tuberculosis, viral hepatitis, hepatic function and pregnancy status. If the patient has an absolute lymphocyte count of <500 cells/mm³, an absolute neutrophil count <1,000 cells/mm³ or a hemoglobin level of <8 g/d, interrupt or avoid initiating therapy with upadacitinib.

Upadacitinib has a boxed warning regarding serious infections, mortality, malignancy, major adverse cardiovascular events and thrombosis. A risk evaluation and mitigation strategy is included with its dosing.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. Supplemental approval letter: Rinvoq (upadacitinib) extended-release tablets for pJIA and psoriatic arthritis in patients at least 2 years old. U.S. Food & Drug Administration. 2024 April 26.
2. New drug application approval letter: Rinvoq LQ (upadacitinib) oral solution. U.S. Food & Drug Administration. 2023 Apr 26.
3. Rinvoq (upadacitinib) now available for pediatric patients two years and older with polyarticular juvenile idiopathic arthritis and psoriatic arthritis [news release]. AbbVie.  2023 Jun 4.
4. New drug application approval letter: Rinvoq (upadacitinib) extended-release tablets. U.S. Food & Drug Administration. 2019 Aug 16.
5. Supplemental approval letter: TNF blocker intolerance indication for Rinvoq (upadacitinib) injection. U.S. Food & Drug Administration. 2021 Dec 14.
6. Highlights of prescribing information: Rinvoq (upadacitinib). U.S. Food & Drug Administration. 2023 May 18.
7. Highlights of prescribing information: Rinvoq LQ (upadacitinib). U.S. Food & Drug Administration. 2024 Apr 26.
8. Brenner H, Horneff G, Foeldvari I, et al. Safety and efficacy of upadacitinib for pediatric patients with polyarticular course juvenile idiopathic arthritis: An interim analysis of an open-label, phase 1 trial [OP 0164]. Ann Rheum Dis. 2023;82:108–109.