Subcutaneous Orencia safe, effective for polyarticular-course JIA
Subcutaneous abatacept used to treat polyarticular-course juvenile idiopathic arthritis improved symptoms, reached target therapeutic exposures across age and weight groups and was well tolerated over a 24-month period, according to findings published in Arthritis and Rheumatology.
“Abatacept, which selectively modulates the CD80/CD86:CD28 co-stimulatory signal required for full T-cell activation, has a distinct mechanism of action upstream of currently available treatments for rheumatic diseases,” Hermine I. Brunner, MD, MSc, MBA, of the Cincinnati Children’s Hospital Medical Center, and colleagues wrote. “In adults with rheumatoid arthritis (RA), IV abatacept inhibits structural damage, reduces disease progression, and improves function and health-related quality of life, with good safety and tolerability.”
To evaluate the pharmacokinetics, safety and effectiveness of subcutaneous abatacept (Orencia, Bristol-Myers Squib) among patients with polyarticular-course juvenile idiopathic arthritis (JIA) during a 24-month period, the researchers conducted a phase-3, two-part, international, study across 48 centers. In the first cohort, the researchers recruited 173 participants aged 6 to 17 years, while cohort two included 46 children aged 2 to 5 years. All participants were patients with polyarticular-course JIA who failed at least one disease-modifying antirheumatic drug.
Patients in both cohorts received weight-tiered subcutaneous abatacept in weekly doses. Those weighing 10 kg to less than 25 kg received 50 mg; those 25 kg to less than 50 kg received 87.5 mg; and those weighing 50 kg or more received 125 mg. Patients who responded to treatment, as defined by the JIA-American College of Rheumatology criteria 30 (JIA-ACR30), at month 4 could receive subcutaneous abatacept to month 24. The primary endpoint was abatacept steady-state serum trough concentration (Cminss) in the first cohort at month 4. Other outcomes included JIA-ACR30, 50, 70, 90, 100 and inactive disease status and median Juvenile Arthritis Disease Activity Score (JADAS)71-C-reactive protein (CRP) over time, immunogenicity and safety.
According to the researchers, median abatacept Cminss at 4 and 24 months was above the target therapeutic exposure — 10µg/ml — in both patient groups. In cohort one, the JIA-ACR30, 50, 70, 90, 100 and inactive disease responses at month 4 were 83.2%, 72.8%, 52.6%, 28.3%, 14.5% and 30.1%, respectively. Meanwhile, the same responses in cohort two 89.1%, 84.8%, 73.9%, 58.7%, 41.3% and 50%, respectively. In both groups, these responses were maintained to month 24.
Patients in cohort one demonstrated an improved median JADAS71-CRP of 21 to 4.6 from baseline to month 4. In the second cohort, median JADAS71-CRP improved 18.1 to 2.1 during the same period. There were no unexpected adverse events; 2.3% of patients in cohort one, and 8.7% of those in cohort two, developing anti-abatacept antibodies.
“Abatacept is seldom used to treat polyarticular-course JIA early in the disease course,” Brunner and colleagues wrote. “The results from cohort two reported here, in which abatacept treatment was initiated in patients with a median disease duration of only 0.5 years, provide valuable data on the early introduction of abatacept; notably, JIA-ACR response rates were consistently higher in cohort two than in cohort one.” – by Jason Laday
Disclosure: The researchers report funding from Bristol-Myers Squibb. Brunner reports consulting fees from AstraZeneca, Bristol-Myers Squibb, Genentech, Janssen, Novartis, Pfizer, Sanofi and Takeda, as well as speaking fees from Genentech and Novartis.