Treatment with Orencia (abatacept) was effective and well-tolerated at four months in children and adolescents with polyarticular juvenile idiopathic arthritis (pJIA) who were intolerant or unresponsive to methotrexate, Phase 3 trials show.
Given these results, stand-alone therapy with Orencia can be considered when prior biologic therapy is ineffective and the use of methotrxate is inappropriate, the researchers said.
Favorable efficacy and safety results at 24 months of treatment have previously been reported from this trial (NCT01844518), which is testing the subcutaneous, or under-the-skin, delivery of Orencia in pJIA patients.
Nicolino Ruperto, MD, presented the updated findings at the 2019 American College of Rheumatology (ACR) / Association for Rheumatology Professionals (ARP) Annual Meeting, held recently in Atlanta. The study was titled “Subcutaneous or Intravenous Abatacept Monotherapy in Pediatric Patients with Polyarticular-Course JIA: Results from Two Phase III Trials.”
Conventional disease-modifying antirheumatic drugs (DMARDs) such as methotrexate are typically the first-line therapy in pJIA. If no response is seen after 2-3 months, a biological DMARD like Humira (adalimumab) or Actemra (tocilizumab) may be added. Yet, patients may be intolerant or show an inadequate response to these DMARDs.
Bristol-Myers Squibb‘s Orencia is a different biological DMARD, which works by blocking an earlier step in the disease process. While Humira and Actemra suppress signals that amplify inflammation, Orencia targets the activation of T-cells, a type of immune cell that is key for the autoimmune reactions in the inside lining of the joints, called the synovium.
In the European Union, Orencia is approved for the treatment of pJIA patients not younger than 2 in combination with methotrexate, or on its own in those who cannot take methotrexate.
The team conducted two Phase 3 trials, both sponsored by Bristol-Myers Squibb.
The trial testing subcutaneous delivery included 219 pJIA patients, ages 2-17, who had failed treatment or were intolerant to another DMARD. All received the therapy every week for 4 months. The Orencia dose depended on the patients’ weight. The children received 50 mg if they were between 10 and 25 kg (22 to 55 pounds), 87.5 mg if they weighed 25 to 50 kg (55-110 pounds), and 125 mg if their weight was 50 kg (110 lbs) or more.
To evaluate disease status, the researchers used JIA-American College of Rheumatology (JIA-ACR) criteria. It consists of six core criteria: 1) physician’s global assessment of disease activity; 2) parent/patient assessment of overall well-being; 3) the number of joints with active arthritis; 4) the number of joints with limited range of motion; 5) functional ability; and 6) erythrocyte sedimentation rate (ESR), a marker of inflammation.
After four months, patients achieving JIA-ACR30 criteria — indicating some improvements of at least 30% — could receive Orencia for another 20 months. JIA-ACR30 specifically means 30% or greater improvement from the start of treatment, or baseline, in three of the six criteria. Meanwhile, only one of the remaining variables can worsen by more than 30%.
The other Phase 3 study (NCT00095173) tested Orencia delivered intravenously, or into the vein. A total of 190 pediatric patients with pJIA, ages 6-17, were enrolled. All had prior treatment failure with a DMARD or were intolerant to this type of therapy.
The participants received Orencia for four months — period A. Those achieving JIA-ACR30 criteria by that point were then randomly assigned to receive either Orencia or a placebo every 4 weeks for 6 months or until a disease flare occurred — period B. Participants could still receive Orencia beyond this timepoint in a five-year follow-up.
The results at four months showed no additional benefits from adding Orencia to methotrexate compared with taking Orencia alone. Flare rates were comparable between Orencia with methotrexate (18.8%) and Orencia alone (25%) in period B of the trial testing IV delivery.
Also at four months and in both studies, the clinical efficacy of the combination was similar to that of Orencia alone in participants achieving pJIA-ACR criteria with intolerance to methotrexate or who failed treatment with this therapy. This indicates that Orencia can replace methotrexate in this patient population, the researchers said.
Participants who had never been treated with a biological DMARD showed a superior clinical response compared with those who had previously used this type of treatment. This effect was independent of simultaneous use of methotrexate in both trials.
The rates of reported adverse effects were comparable between Orencia alone and with methtroxate, and between participants who had not received a biologic DMARD compared to those who had.
Anti-Orencia antibodies, which may neutralize the treatment’s therapeutic effects, were not observed following Orencia monotherapy in the study testing subcutaneous administration. No impact on Orencia’s efficacy was seen in the few patients with such antibodies in the trial assessing IV delivery.
“[Orencia] monotherapy was effective and well tolerated in [patients] with pJIA intolerant to MTX [methotrexate] or when prior MTX was not effective,” the researchers said. “In addition, abatacept [Orencia] monotherapy can be considered for use in those with prior biologic therapy if MTX use is inappropriate.”