Baricitinib Promising for Juvenile Idiopathic Arthritis

EULAR 2022 (VIRTUAL)—A study found oral baricitinib (Olumiant) significantly reduced the time to and frequency of flares in patients aged 2–18 years with juvenile idiopathic arthritis (JIA).¹ The findings of the study were presented by Athimalaipet Ramanan, MD, FRCPCH, FRCP, a consultant pediatric rheumatologist at Bristol Royal Hospital for Children and Royal National Hospital for Rheumatic Diseases, Bath, U.K., and Bristol Royal Hospital for Children, Bristol Medical School, Bristol, U.K.

Baricitinib is a Janus kinase (JAK) ½ selective inhibitor. In May 2018, the U.S. Food & Drug Administration (FDA) approved the agent to treat adults with moderate to severe active RA for whom one or more tumor necrosis factor (TNF) antagonist therapies had proved inadequate.² In a phase 3 study, Ramanan et al. investigated baricitinib’s safety and efficacy in pediatric patients with JIA for whom conventional or biologic disease-modifying anti-rheumatic drugs (DMARDs) had proved inadequate.

Participants in this double-blind, withdrawal study included patients with extended oligoarticular or polyarticular JIA, enthesitis-related arthritis (ERA) or juvenile psoriatic arthritis (jPsA) according to the International League of Associations for Rheumatology (ILAR) criteria.

Study Design

The study was divided into three periods: a two-week pharmacokinetic and safety assessment; a 12-week, open-label, lead-in period; and a 32-week, double-blind withdrawal period. Safety and dosing were confirmed during the pharmacokinetic and safety assessment period. Patients enrolled in the open-label, lead-in period then received age-based, once-daily doses of baricitinib. Patients who achieved a JIA ACR30 response at week 12 entered the study’s double-blind withdrawal phase. In the double-blind withdrawal period, patients were randomized in a 1:1 ratio to continue baricitinib treatment or begin baricitinib withdrawal, receiving placebo until disease flare or week 32.

The primary study end point was the time to flare during the double-blind withdrawal period. Secondary end points included the proportion of patients experiencing a flare during the double-blind withdrawal period and the JIA ACR30/50/70/90 response rates at week 12. Survival curves were estimated using the Kaplan-Meier method.

The Results

In total, 219 patients entered the study’s second phase—the 12-week, open-label, lead-in period—and 163 patients entered the 32-week, double-blind withdrawal period.

At week 12, 76.3% of patients achieved a JIA ACR30 response, 63.5% of patients achieved a JIA ACR50 response, 46.1% of patients achieved a JIA ACR70 response and 20.1% of patients achieved a JIA ACR90 response. During the double-blind withdrawal period, the proportion of patients who experienced a disease flare was significantly lower in the baricitinib treatment group (17.1%) than the placebo group (50.6%; P<0.001).

In the pharmacokinetic and safety assessment and open-label, lead-in parts of the study, 126 patients (57.3%) reported treatment-emergent adverse events, and six patients (2.7%) reported at least one serious adverse event. The most common treatment-emergent adverse events in both groups were nasopharyngitis (n=19; 8.6%), headache (n=14; 6.4%), arthralgias (n=12; 5.5%), upper respiratory tract infection (n=11; 5%) and nausea (n=11; 5%). Serious adverse events included arthralgias (n=1; 0.5%), joint destruction (n=1; 0.5%), joint effusion (n=1; 0.5%), JIA (n=1; 0.5%), musculoskeletal chest pain (n=1; 0.5%) and decreased appetite (n=1; 0.5%). One case of herpes virus (0.5%) and one case of herpes zoster (0.5%) were also reported.

In the study’s double-blind withdrawal period, at least one treatment-emergent adverse event was reported for patients who received placebo (n=38; 46.9%) and for patients treated with baricitinib (n=54; 65.9%). Three (3.7%) and four (4.9%) serious adverse events occurred in patients who received placebo and baricitinib, respectively. Due to the study design, the mean number of weeks of exposure was higher in the baricitinib group (26.3 weeks) compared with the placebo group (18.9 weeks) during this study period.

No deaths, cardiovascular events or uveitis were reported, and no new safety signals were identified during the study.

In this study, baricitinib significantly reduced time to JIA flare and frequency of JIA flares in young patients, with improved JIA ACR response scores in most patients within 12 weeks. The safety findings were consistent with the known safety profile of baricitinib in adults with RA.

These results support the use of baricitinib to treat patients aged 2–18 years with signs and symptoms of JIA for whom conventional or biologic DMARDs have proved inadequate.

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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. Ramanan A, Quartier P, Okamoto N, et al. Baricitinib in juvenile idiopathic arthritis: A phase 3, double-blind, placebo-controlled, withdrawal, efficacy and safety study [LB0002]. Ann Rheum Dis. 2022:81(suppl 1): 207–208.
2. New drug application approval letter: Olumiant (baricitinib). U.S. Food & Drug Administration. 2018 May 31.