Bristol-Myers Squibb Company said the US Food and Drug Administration (FDA) has approved Orencia (abatacept) for reducing signs and symptoms in paediatric patients six years and older with moderately to severely active polyarticular juvenile idiopathic arthritis (JIA). Orencia may be used as monotherapy or concomitantly with methotrexate (MTX).

The approval is based on the AWAKEN (Abatacept Withdrawal study to Assess efficacy and safety in Key Endpoints in juvenile idiopathic arthritis Not responding to current treatment) trial, which evaluated the efficacy and safety of Orencia (abatacept) in patients six to 17 years of age with moderately to severely active polyarticular JIA who had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs), such as MTX or TNF antagonists.

Orencia should not be administered concomitantly with tumour necrosis factor (TNF) antagonists and is not recommended for use concomitantly with other biologic rheumatoid arthritis (RA) therapy, such as anakinra, according to a company press release. This new indication for Orencia provides significant evidence of its durable efficacy and long-term safety in paediatric patients, including those initiating biologic therapy for the first time. The safety and efficacy of Orencia in JIA were assessed in a three-part study through one year. The approval of Orencia in JIA represents the ongoing commitment of Bristol-Myers Squibb in this therapeutic area, it said.

"In a JIA clinical trial, Orencia provided meaningful and sustained improvements in this patient population across three major sub-types of JIA through one year," said Edward H. Giannini, M.Sc., Dr.P.H., Professor of Paediatrics, Division of Rheumatology, Cincinnati Children's Hospital Medical Centre, OH.

"Juvenile idiopathic arthritis is the most prevalent form of arthritis in children," said Elliott Sigal, M.D., Ph.D., executive vice president, chief scientific officer and president, Research and Development, Bristol-Myers Squibb. "This new indication for Orencia offers another treatment option to help improve signs and symptoms of this serious disease in paediatric and adolescent patients."

In addition to the approval for JIA, Bristol-Myers Squibb has added a post-marketing safety section to the package insert. This section states that the post-marketing adverse event profile that was observed in adult RA patients did not differ from that seen in the clinical trials of adult RA patients. The FDA also has revised the adult indication to remove the requirement that patients must first fail at least one DMARD before initiating therapy with Orencia. The new indication statement is: Orencia is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage and improving physical function in adult patients with moderately to severely active RA. Orencia may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists. Orencia should not be administered concomitantly with TNF antagonists and is not recommended for use concomitantly with other biologic RA therapy, such as anakinra. The revised adult indication means that Orencia is an appropriate option for patients with moderate-to-severe RA, regardless of prior treatment received.

The AWAKEN trial was a three-part study which included patients with subtypes of JIA that at disease onset included Oligoarticular JIA (16 per cent), Polyarticular JIA (64 per cent; 20 per cent were rheumatoid factor (RF) positive) and Systemic JIA with polyarticular course (20 per cent) who had not responded adequately to other JIA therapies. In the first phase of this study (Period A), a total of 190 patients aged six to 17 years, with disease duration of approximately four years with moderately to severely active disease at study entry, were enrolled in this open-label, four-month, lead-in phase of the study. The majority (70 per cent) of these study patients were new to biologic treatments. Nearly 30 per cent of patients had previously had an inadequate response to a TNF antagonist or anakinra. Patients received ORENCIA (abatacept) intravenously (10 mg/kg; maximum 1,000 mg) on Days 1, 15, 29 and every month thereafter. Response was assessed utilizing the ACR Paediatric 30 definition of improvement, defined as greater than or equal to 30 per cent improvement in at least three of the six JIA core set variables and greater than or equal to 30 per cent worsening in not more than one of the JIA core set variables.

The primary endpoint of the study was time to occurrence of disease flare. Disease flare was defined as a greater than or equal to 30 per cent worsening in at least three of the six JIA core set variables with greater than or equal to 30 per cent improvement in not more than one of the six JIA core set variables; greater than or equal to two centimeters of worsening of the Physician or Parent Global Assessment was necessary if used as one of the three JIA core set variables used to define flare, and worsening in greater than or equal to two joints was necessary if the number of active joints or joints with limitation of motion was used as one of the three JIA core set variables used to define flare.

In patients receiving Orencia treatment throughout the study (Period A, Period B and the open-label extension Period C), the proportion of ACR Pedi 30, 50 and 70 responders remained consistent through one year.

In the open-label, lead-in (Period A) and double-blind (Period B) phases of the study, the adverse reactions in paediatric patients were similar in type and frequency to those seen in adult patients. This was also seen in patients who participated in the open-label (Period C) extension period.

Orencia is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA. Orencia may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists. Orencia is also indicated for reducing signs and symptoms in paediatric patients aged six years and older with moderately to severely active polyarticular JIA. Orencia may be used as monotherapy or concomitantly with MTX in paediatric patients. Orencia should not be administered concomitantly with TNF antagonists. Orencia is not recommended for use concomitantly with other biologic RA therapy, such as anakinra.