SAT0397 THE LONG-TERM SAFETY OF ETANERCEPT IN CHILDREN WITH POLYARTICULAR OR SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS.

E. H. Giannini¹, N. T. Ilowite², D. J. Lovell¹, C. A. Wallace³, C. E. Rabinovich⁴, A. O. Reiff⁵, G. Higgins⁶, Y. Chon⁷, S. Lin⁷
¹, Cincinnati Children's Hospital Medical Center, Cincinnati, ², Schneider Children's Hospital, New Hyde Park, ³, Children's Hospital and Regional Medical Center, Seattle, ⁴, Duke University Medical Center, Durham, ⁵, Children's Hospital of Los Angeles, Los Angeles, ⁶, Ohoi State University and Children's Hospital, Columbus, ⁷, Amgen, Thousand Oaks, United States

Background: Etanercept has been approved for use in children with polyarticular course juvenile rheumatoid arthritis (JRA). Analyses of long-term safety data in children with JRA will provide important insight into the prolonged use of etanercept in these patients.
Objectives: To evaluate the long-term safety of etanercept in children with polyarticular or systemic JRA.
Methods: This 3-year, open label, non-randomized registry included patients between 2 and 18 years of age with polyarticular course or systemic JRA, who initiated etanercept and/or methotrexate for ≤ 6 months. JRA patients treated with either methotrexate (MTX), etanercept (ETN), or methotrexate and etanercept in combination (MTX/ETN) were eligible. Co-administration of one or more non-biologic DMARDs was allowed.
Etanercept was administered subcutaneously at a dose of 0.4 mg/kg (to a max dose of 25 mg) twice weekly for up to 36 months. Safety data was reported for all patients including exposure adjusted rates of serious adverse events (SAEs), medically important infections (MIIs), and opportunistic infections (OIs). Events of interest including malignancy, sepsis, autoimmune disorders, and death were also reported. Joint counts and the Physician’s Global Assessment (PhGA) were used to assess efficacy.
Results: A total of 601 patients enrolled of which 198 received MTX, 105 received etanercept (ETN), and 298 received MTX/ETN. Most patients were female (450/601, 75%) and Caucasian (446/601, 74%). The mean ages (median) for patients receiving MTX, ETN, or MTX/ETN were 9 (9), 11 (11), and 10 (10) years respectively. Most patients had polyarticular onset arthritis (356/601, 59%). A total of 131 MTX patients (66%), 51 ETN patients (49%), and 146 MTX/ETN (49%) patients discontinued the registry. In the MTX, ENT, and MTX/ENT groups respectively, 24 (12%), 7 (7%), and 11 (4%) patients discontinued because of remission and 35 (18%), 7 (7%), and 51 (17%) discontinued because of an insufficient therapeutic effect. A total of 159 patients (26%) have completed 3 years of observation to date. The rates of SAEs per 100 pt-yrs were 5.25, 8.36, and 5.78, and the rates of MIIs per 100 pt-yrs were 0.95, 1.97, and 1.98 respectively, for patients receiving MTX, ETN, or MTX/ETN. A total of 2 OIs (0.48 per 100 pt-yrs) were reported in patients receiving MTX and 3 OIs were reported in patients receiving MTX/ENT (0.50 per 100 pt-yrs). One case of lupus (MTX) and 2 cases of sepsis (ETN and ETN/MTX) were reported. No cases of lymphoma, malignancy, tuberculosis, or death were reported. In addition, the median number of active joints reported was decreased at 36 months as compared to baseline in patients receiving MTX (6 to 0), ETN (5 to 0), and MTX/ETN (6 to 1). The median PhGA scores were also improved over baseline values as PhGA scores decreased in all patients after 36 months of therapy (MTX, 4 to 1; ETN, 3 to 1; MTX/ETN, 4 to 1).

Conclusion: Safety data and limited efficacy data from this ongoing registry support the use of etanercept in this patient population for up to 3 years.