A PHASE I SAFETY STUDY OF COMBINATION TREATMENT WITH PEGYLATED SOLUBLE TUMOR NECROSIS FACTOR RECEPTOR TYPE I (PEG STNF-RI) AND ANAKINRA (INTERLEUKIN-1 RECEPTOR ANTAGONIST, IL-1RA) IN PATIENTS WITH RHEUMATOID ARTHRITIS

J.R. Caldwell , H. Offenberg , D. Furst , N.P. Lam , G. Jayne , T. Joh , M. Davis , C.K. Edwards III Rheumatology, Florida Arthritis & Allergy, Daytona Beach, Rheumatology, Gainesville, Rheumatology, Virginia Mason Research Center, Seattle, Development, Amgen, Inc, Thousand Oaks, United StatesObjectives: The safety of combination treatment with pegsunercept and anakinra in patients with rheumatoid arthritis (RA) was assessed in a Phase 1, double-blind, placebo-controlled, dose escalation study at 3 US centers.Methods: Weekly injections of 10, 30, 60 mg, or twice weekly injections of 800 μg/kg of pegsunercept, or placebo, plus daily injections of anakinra (100 mg) were given for 8 weeks following a single-dose treatment phase. Eligible patients had active RA (defined by the ACR criteria) of at least 6 months of duration, > 6 swollen joints and either > 9 tender/painful joints, CRP > 1.5 mg/dL, ESR > 28 mm/hr, or morning stiffness > 45 minutes. Patients were required to withdraw from DMARDs for >= 4 weeks prior to entry and throughout the study. Stable doses of corticosteroids and NSAIDs were allowed. Safety was evaluated by summary statistics for adverse events (AEs) and infectiousepisodes.Results: A total of 16 patients received the combination of pegsunercept + anakinra and 4 patients received placebo + anakinra (control group). Baseline characteristics were similar between the 2 groups. Two patients who received pegsunercept + anakinra discontinued early due to joint pain and consent withdrawal. The incidence of AEs observed in the pegsunercept + anakinra group and the control group were similar: injection site reactions (62.5% vs.100%, respectively), gastrointestinal (GI) complaints (50% vs. 75%, respectively), and respiratory complaints (37.5% vs. 50%, respectively). Four serious AEs were reported among the pegsunercept + anakinra treated patients (1 GI hemorrhage, 1 abdominal pain, 1 syncope, 1 fracture due to a fall). None of the events was judged to be related to study drugs or resulted in withdrawal from the study. No serious AEs were reported in the control group. Five (31.3%) patients who received pegsunercept + anakinra experienced 6 mild to moderate infectious episodes (1 upper respiratory infection, 1 bronchitis, 1 sinusitis, 2 urinary tract infections, 1 bacterial vaginitis), while one patient in the control group experienced a mild infectious episode (phlebitis). No serious infectious episodes were reported in either of the treatment groups.Conclusion: Mild to moderate infectious episodes occurred in patients receiving the combination of pegsunercept and anakinra. However, no serious infectious episodes were reported during this 8-week, Phase I study. Larger studies that will further characterize the safety and efficacy of the combination treatment with pegsunercept and anakinra are ongoing in patients with RA.Citation: , volume , supplement , year 2002, page Session: Rheumatoid arthritis – Treatment 2