DOSE-RANGE AND DOSE-FREQUENCY STUDY OF RECOMBINANT HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST IN PATIENTS WITH RHEUMATOID-ARTHRITIS

Objective. To preliminarily evaluate the safety and efficacy of differ ent dose levels and dosing frequencies of recombinant human interleuki n-1 receptor antagonist (rHuIL-1Ra) in the treatment of patients with rheumatoid arthritis (RA). Methods. One hundred seventy-five patients with active RA were enrolled in a randomized, double-blind trial of rH uIL-1Ra administered by subcutaneous injection. There were 9 treatment groups in the trial. During the initial 3-week treatment phase, patie nts were treated with 20, 70, or 200 mg rHuIL-1Ra, administered either once, 3 times, or 7 times per week followed by a 4-week maintenance p hase, during which all patients received the treatment-phase dose once per week. To maintain the blindness of the study, patients received d aily injections of either rHuIL-1Ra or placebo on the days rHuIL-1Ra w as not administered. Results. Recombinant HuIL-1Ra was well tolerated. The most frequent adverse event was injection-site reactions, which w ere reported in 62% of patients and caused 8 patients (5%) to withdraw prematurely from the study. Five patients (3%) developed serious adve rse reactions unrelated to dose or dosing frequency. Due to the lack o f a placebo arm and to the multiple small treatment groups, a definiti ve statement regarding efficacy could not be made. However, by the end of the 3-week treatment phase, daily dosing appeared more effective t han weekly dosing when assessed by the number of swollen joints, the i nvestigator and patient assessments of disease activity, pain score, a nd C-reactive protein levels. Conclusion. These preliminary data sugge st that rHuIL-1Ra may be safely administered by subcutaneous injection to RA patients. The frequency of dosing appears to be important in de termining clinical response, with daily administration providing the m ost benefit. A placebo-controlled trial is in progress to further asse ss the clinical usefulness and to better define appropriate doses of r HuIL-1Ra in patients with RA.