Orencia Safe, Effective for Children with Polyarticular JIA, Phase 3 Trial in Japan Confirms

Orencia Safe, Effective for Children with Polyarticular JIA, Phase 3 Trial in Japan Confirms

Treatment with Orencia (abatacept) is well-tolerated and effective in managing disease activity in children with polyarticular juvenile idiopathic arthritis (JIA), according to results from a Phase 3 clinical trial conducted in Japan.

Nearly all patients responded positively to Orencia, showing signs of disease activity reduction at 16 weeks of treatment, and achieving even better responses after one year.

Trial results were described in the study, “Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study,” published in the journal Pediatric Rheumatology.

Orencia, marketed by Bristol-Myers Squibb, has been an approved therapy for children with polyarticular JIA in the United States since 2008. However, the regulatory agency in Japan has only recently recognized the therapeutic potential of Orencia for this population, approving it in February 2018.

The open-label Phase 3 trial (NCT01835470) was designed to investigate Orencia’s efficacy, distribution, and metabolization in the body (pharmacokinetics), as well as its safety, in Japanese children with polyarticular JIA.

The trial enrolled 20 patients ages 5 to 16, who had not responded or who were intolerant to one or more prior lines of treatment with methotrexate or another biologic therapy, including Actemra (tocilizumab), adalimumab (sold as Humira, among others), etanercept (Enbrel, among others), or anti-TNF agents.

Patients received intravenous (into-the-vein) injections of Orencia at the start of the study and then at two and four weeks, followed by treatment every four weeks thereafter, at a dose based on the patient’s weight at each visit. During the study, simultaneous use of methotrexate was also allowed.

Researchers evaluated patients’ response to treatment as determined by the American College of Rheumatology (ACR) pediatric (Pedi) 30 criteria. This considers a positive response in patients as at least a 30% improvement from the study start in three of the six JIA core variables, with no more than a 30% worsening in one of the remaining variables.

This core set of JIA outcome measures consists of the number of active joints, number of joints with limited range of motion, physician’s global assessment of disease severity, patient assessment of overall well-being, parent assessment of physical function, and acute phase reactants (inflammation markers).

Researchers also evaluated ACR Pedi 50, 70, and 90 criteria that require at least a 50%, 70%, or 90% improvement respectively in at least three core variables, with no more than a 30% worsening in more than one variable.

All 20 patients enrolled completed the initial 16-week treatment period, with two of them discontinuing treatment after this due to lack of efficacy or patient decision.

At this point, 90% of the patients were responding positively to Orencia, with a response falling under the ACR Pedi 30 criteria. In addition, the proportion of patients meeting ACR 50, 70, and 90 response rates were 75%, 70%, and 35% respectively. After one year of treatment with Orencia, these response rates rose for all categories, reaching 88.9%, 88.9%, 83.3%, and 66.7% for ACR Pedi 30, 50, 70, and 90, respectively.

Approximately 25% of the patients achieved inactive disease, defined as no active joints, a physician’s global assessment (PGA) score of 10 mm or less and a C-reactive protein (CRP) testing of 0.3 mg/dL or less at 16 weeks. This percentage increased to 44% of patients after one year of treatment.

Improvements were also seen in physical ability across various daily activities, such as dressing, eating, walking, grip, and other common activities, after 12 weeks of treatment, assessed by CHAQ-DI survey.

In addition, 15% of patients reached disease remission and 45% had minimal disease activity after 16 weeks, according to the JADAS27-CRP score of disease activity. A year later, the proportion of patients fulfilling these criteria had increased to 50% and 78% respectively.

In general, intravenous administration of Orencia was well-tolerated both in the short-term 16-week period and over the one-year follow-up. All adverse events related to the treatment were mild or moderate, with the exception of one case of severe gastroenteritis (inflammation of the gastrointestinal tract).

The most common adverse events reported were infections, the most frequent being nasopharyngitis, pharyngitis, and flu. No deaths, malignancies, autoimmune disorders, or withdrawals due to adverse events were reported through the entire study.

After 16 weeks, no patients had developed an immune response against Orencia. In the subsequent period, only one patient tested positive for antibodies against the treatment, although this was not associated with a loss of effectiveness or any particular safety concerns.

“These data suggest that intravenous [Orencia] treatment provides an effective and well-tolerated treatment option for Japanese patients with active polyarticular JIA who do not tolerate existing first-line treatment,” the researchers concluded.

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