AT THE ACR ANNUAL MEETING
WASHINGTON (FRONTLINE MEDICAL NEWS) – Abatacept achieved promising results in patients with psoriatic arthritis through 24 weeks of treatment in a placebo-controlled, phase III trial.
Based on these results of the trial, called ASTRAEA, the manufacturer of abatacept (Orencia) and sponsor of the study, Bristol-Myers Squibb, has submitted a Supplemental Biologics Application with the Food and Drug Administration as well as a Variation Application with the European Medicines Agency for an extended indication that includes the treatment of adult psoriatic arthritis (PsA).
“I am thrilled to present these results in PsA,” said lead investigator Philip J. Mease, MD, of Swedish Medical Center, Seattle. “Many patients with PsA have an inadequate response to available medications. There is an unmet need for new targeted therapies for PsA. Abatacept, a selective T-cell co-stimulation modulator, is a potential new therapy for PsA with a distinct mechanism of action upstream of currently available agents.”
ASTRAEA ( Efficacy and Safety of Subcutaneous Abatacept in Adults With Active Psoriatic Arthritis) enrolled 424 patients who met ACR PsA criteria and had evidence of active arthritis and psoriasis, plus inadequate response or intolerance to at least one nonbiologic disease-modifying antirheumatic drug (DMARD). The patients, of whom 60% failed prior tumor necrosis factor inhibitor (TNFi) treatment, were randomized to abatacept subcutaneous injection 125 mg/week or placebo. Median age was around 50 years, and about 50% were males. A total of 60% were on concomitant methotrexate.
“This was an active disease population, with about two-thirds having elevated C-reactive protein,” Dr. Mease noted at the annual meeting of the American College of Rheumatology.
A total of 39.4% of abatacept-treated patients achieved the primary endpoint of 24-week ACR20 response versus 22.3% of placebo patients (P less than .001). Improvement on ACR20 continued out to week 44.
Patients who were TNFi naive had better ACR20 responses than did those previously exposed to TNFi, he said. An ACR20 response occurred in 44% of TNFi-naive patients on abatacept, compared with 36.4% of TNFi-exposed patients. The same pattern was observed for ACR50 and ACR70 response rates.
A linear relationship was seen between response to abatacept and CRP baseline level, with a greater degree of response in those with elevated CRP.
Numerical trends favored abatacept for 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) responses, and X-ray assessment of structural damage. “We saw complete resolution of enthesitis and dactylitis at week 24 in 30%-40% of patients taking abatacept, and responses improved over time,” Dr. Mease told listeners. “Skin responses on the PASI 50 and PASI 75 were modest and not as good as we see with other agents,” Dr. Mease said.
Few serious adverse events were reported. There were three serious infections in the abatacept group and two in the placebo group at week 24.
“These data are consistent with phase II data. Overall, we saw beneficial trends with abatacept for all key endpoints, and the benefits were observed in both TNFi-exposed and TNFi-naive patients subgroups. Abatacept may be an appropriate option for PsA patients to try, especially those with musculoskeletal manifestations [given the modest responses in skin],” Dr. Mease said.
All of the ASTRAEA investigators had industry relationships, including some with Bristol-Myers Squibb. Two were employees of the company.