Juvenile RA/Pediatric Rheumatology
Sangeeta Sule, M.D.
Abstract 723: A Randomized, Multi-Center, Blinded, Placebo-Controlled Study With an Open-label Run-in Period to Evaluate Anakinra in Polyarticular-Course Juvenile Rheumatoid Arthritis
Authors: N. Ilowite1, A. Reiff2, S. Rudge3, M. Punaro4, A. Martin5, R. Allen6, T. Harville7, T. Bevirt8, G. Aras8, B. Appleton8. 1Children's Hospital at Montefiore, Bronx, NY; 2Childrens Hosp., Los Angeles, CA; 3Hutt Hosp., Lower Hutt, New Zealand; 4University of Texas, Dallas, TX; 5Healthcare Research Consultants, Tulsa, OK; 6Royal Children's Hosp., Parkville, Australia; 7Arkansas Children's Hosp., Little Rock, AR; 8Amgen, Thousand Oaks, CA
Purpose: To evaluate the efficacy, safety, and PK of daily, single, subcutaneous injections of anakinra (ANK) in children with polyarticular juvenile rheumatoid arthritis (JRA)
Methods: Children aged 2-17 years old with a minimum weight of 10 kg with JRA were enrolled. Patients had to be on stable doses of methotrexate for 6 weeks. Biological therapy was not allowed within 4 weeks of starting study. For the first 12 weeks, patients received open-label treatment with anakinra (1 mg/kg/day, max dose 100 mg/day). At 12 weeks, patients meeting the definition of responder were randomly assigned either placebo or anakinra for an additional 16 weeks.
Results: Of the 86 patients (63 girls, 23 boys) in the open-label phase, 50 entered the double-blind phase. The anakinra treated patients had fewer disease flares compared to placebo (16% vs. 36%, p=NS at week 28). A larger proportion of patients who received anakinra were without disease flare compared to placebo (84% vs. 64%, p=NS). The most common adverse events were headache (24% anakinra vs. 4% placebo), and URI (24% anakinra vs. 20% placebo). No adverse events led to withdrawal of study drug. When plasma anakinra concentrations were normalized to 1 mg/kg, the range of anakinra in JRA patients was comparable to adult RA patients. When normalized to 100 mg (fixed dose), higher anakinra concentrations were seen in JRA patients than in adult RA patients.
Conclusions: Anakinra did not show efficacy compared to placebo in treatment of polyarticular JRA. Even though plasma anakinra concentrations indicated adequate exposure in JRA patients, the small sample size limits interpretation.
Editorial Comments: This study is important in that it notes negative results from a clinical trial. Even though serum concentrations equivalent to adult RA patients were obtained in the JRA patients in the trial, there was no significant treatment effect with anakinra. This dampens enthusiasm for anakinra in the treatment of polyarticular JRA. However, anakinra has been shown to be effective for systemic-onset JRA. This suggests a difference in biological response between polyarticular and systemic-onset JRA.