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Embargoed for Release at 6:15 pm ET , Sunday Oct. 17, 2004

Arthritis News

STUDIES EXPAND EFFICACY OF ETANERCEPT FOR JUVENILE ARTHRITIS PATIENTS

SAN ANTONIO, TEXAS - The efficacy of treatment with etanercept (Enbrel®), already credited with rapid clinical improvements sustained for up to two years in patients with juvenile rheumatoid arthritis, has now been extended to as long as four years, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Antonio, Texas.

To arrive at these results, 69 children with severe juvenile rheumatoid arthritis, average age 10.5 years, who regularly experienced swelling and inflammation in five or more joints and were unresponsive to or unable to take methotrexate, were tracked in a two-part efficacy trial. In part one of the study, these children were given 0.4 mg/kg of etanercept twice a week for three months. Those who satisfied the definition of "response" for this study by having a clinically important decrease in overall disease activity were then randomized into part two of the study, during which they received either etanercept or a placebo for four months or until symptoms flared (whichever came first). Following completion of part two, all patients were allowed to continue or restart treatment with etanercept in the extension study.

As of the last study visit (at least four years of treatment with etanercept), 94 percent of those patients were still showing an improved response and 78 percent demonstrated a dramatic response. Further, the 34 children who remained in the extension study experienced only 0.13 serious adverse events per patient-year and only 0.04 serious infections per patient-year.

Juvenile rheumatoid arthritis, which affects nearly 300,000 children in the United States, is a chronic autoimmune disease that strikes children before age 16, and can cause painful joint swelling, deformity, stunted growth and increased mortality. This can impair a child's ability to take part in physical activities, make daily activities such as schoolwork more difficult, and affect a child's physical appearance. Parents and siblings also are impacted by the psychological and financial stress of a chronic illness in a family member.

"Children with j uvenile rheumatoid arthritis can face the possibility of a lifetime of pain and disability," said Daniel J. Lovell, MD, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, and an investigator in the study. "This is the first time any TNF inhibitor has demonstrated the ability to help children with severe, treatment-resistant juvenile rheumatoid arthritis experience significant improvement in symptoms for as long as four years, with ongoing treatment."

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see www.rheumatology.org/annual.

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Editor's Notes: Dr. Lovell will present this research during a scientific session at the ACR Annual Scientific Meeting from 8:30 - 8:45 pm CT (9:30 - 9:45 am ET) on Tuesday, October 19, in Room 006 of the Henry B. Gonzalez Convention Center.

Presentation Number: 1095

Long-Term Safety and Efficacy Experience with Etanercept (Enbrel ®) in Children with Polyarticular Juvenile Rheumatoid Arthritis

D. Lovell 1, A. Reiff 2, OY Jones 3, R. Schneider 4, EH Giannini 1, for the Pediatric Rheumatology Collaborative Study Group, JB Whitmore 5, B. White 5. 1 Children's Hospital Medical Center, Cincinnati, OH; 2 Los Angeles Children's Hospital, Los Angeles, CA; 3 All Children's Hospital and University of South Florida, St. Petersburg, FL; 4 Hospital for Sick Children and University of Toronto, Toronto, ON, Canada; 5 Amgen Inc, Thousand Oaks, CA

Purpose: Etanercept (ETN) treatment in patients with juvenile rheumatoid arthritis (JRA) results in rapid clinical improvements that are sustained for up to 2 years (1). This report examines safety and efficacy of ETN in patients with JRA after 4 years (yrs) of treatment with ETN.

Methods: Patients with active polyarticular course JRA who were either intolerant or refractory to MTX participated in a two-part efficacy trial with ETN. Patients received 0.4 mg/kg of open-label ETN twice weekly (max 25 mg/dose) for 3 months in part 1. Patients who achieved an ACR Pedi 30 response in part 1 were randomized in part 2 to receive blinded ETN or placebo until disease flare occurred or for 4 months. Patients could continue treatment with ETN in an open-label extension if they completed the efficacy study or discontinued because of inadequate response or disease flare. Patients were permitted to start or taper corticosteroids during the extension. Rates of serious adverse events (SAEs) and serious infections (SIs) were used to assess safety. ACR Pedi scores and standard measures of disease activity were used to assess efficacy.

Results: 69 JRA patients enrolled in the efficacy trial. At baseline, on average, the age was 10.5 yrs, duration of JRA was 5.9 yrs, number of active joints was 28.5, and 36% were receiving corticosteroids (mean dose 6 mg/day). 34 (49%) of these patients remain in the extension study; efficacy data are available for 32 patients who have received ETN for ≥ 4 yrs in the extension. The mean number of active joints was 2.0 at 4 years. The most frequent reasons for drop out were lack of response (n = 8), refusal of parent/guardian or patient (n = 6), and adverse event (n = 5). The rate of SAEs was 0.13 per patient-year (pt-yr), and the rate of SIs was 0.04 per pt-yr, with a total ETN exposure of 225 pt-yrs. The most common SAE was disease flare (n = 8). There were 8 serious infections: gastrointestinal infection, aseptic meningitis, varicella-zoster, herpes zoster, appendicitis, dental abscess, and 2 wound infections. No deaths or malignancies were reported. In those who received ≥ 4 years of ETN treatment, 94% achieved an ACR Pedi 30 response at the last study visit and 78% achieved an ACR Pedi 70 response, with a trend for an increase in response over time that was not attributable to a survivor effect.

Conclusions: ETN offers an acceptable safety profile in patients with JRA. Rates of SAEs and SIs are similar to those seen in adult RA patients treated with ETN. Treatment with ETN results in significant improvements in clinical signs and symptoms of disease and these improvements are sustained for as long as 4 years.
(1) Lovell et al, Arthritis Rheum 2003; 48:218-226

Disclosure: D. Lovell, Amgen 5, 8; Wyeth 8; Centocor 5; Bristol Myers Squibb 5; Abbott 5; A. Reiff, Amgen 5, 8; Wyeth 5, 8; Merck 5, 8; Abbott 2;  O. Jones, None; R. Schneider, Roche Pharmaceuticals 5; E. Giannini, Centocor 2, 5; Amgen 2; Abbott 2; Barr Laboratories 5; Bristol-Myers Squibb 2, 5; J. Whitmore, Amgen Inc 1, 3; B. White, Amgen Inc 1, 3.