RA Treatment - Interleukin 1 receptor antagonist
Abstract 1217 Treatment of Interleukin 1 receptor antagonist in Combination with Methotrexate (MTX) in Rheumatoid Arthritis (RA) Patients
S Cohen, E Hurd, JJ Cush, MH Schiff, ME Weinblatt, LW Moreland, M Bear, W Rich, DP McCabe Dallas TX, Denver CO, Boston MA, Birmingham AL, Thousand Oaks CA
IL-1 is a macrophage derived cytokine found in high quantities in the rheumatoid joint and likely has a central role in the recruitment of inflammatory cells into the joint and the production of proteases that cause joint destruction. A naturally occurring IL-1 receptor antagonist is found in the circulation and IL-1ra is a cloned protein derived from the sequence of the native protein. The current trial examines the efficacy of IL-1ra when added to MTX.
419 patients with active RA were randomized to receive 0.04 2.0 mg/kg of IL-1ra or placebo by daily SC injection for 24 weeks. Patients were required to be on stable doses of MTX between 12.5 mg and 25 mg weekly for 6 months and to have active disease despite MTX. At baseline, average MTX dose was 17 mg/week, disease duration 7 years, 25 mean tender joints and 18 mean swollen joints.
At the 1.0 mg/kg dose, 42% of the IL-1ra/MTX patients responded by ACR 20 criteria at 24 weeks compared with 23% of the placebo/MTX group (p = 0.021). At the 2.0 mg/kg dose, 35% of the IL-1ra/MTX group demonstrated ACR 20 improvement. Using ACR 50, at 1.0 mg/kg, 24% of the IL-1ra/MTX group responded compared with 4% of the placebo group.
Editorial Comment: The trial demonstrates that IL-1ra is safe and effective when added to MTX in patients not responding to MTX alone. These results need to be examined for durability in longer trials or extensions to the current protocol. The lack of dose response is concerning and potential mechanisms for this should be investigated.