Objective. To preliminarily evaluate the safety and efficacy of different dose levels and dosing frequencies of recombinant human interleukin‐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 rHuIL‐1Ra administered by subcutaneous injection. There were 9 treatment groups in the trial. During the initial 3‐week treatment phase, patients 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 phase, during which all patients received the treatment‐phase dose once per week. To maintain the blindness of the study, patients received daily injections of either rHuIL‐1Ra or placebo on the days rHuIL‐1Ra was not administered.

Results. Recombinant HuIL‐1Ra was well tolerated. The most frequent adverse event was injection‐site reactions, which were reported in 62% of patients and caused 8 patients (5%) to withdraw prematurely from the study. Five patients (3%) developed serious adverse reactions unrelated to dose or dosing frequency. Due to the lack of a placebo arm and to the multiple small treatment groups, a definitive statement regarding efficacy could not be made. However, by the end of the 3‐week treatment phase, daily dosing appeared more effective than weekly dosing when assessed by the number of swollen joints, the investigator and patient assessments of disease activity, pain score, and C‐reactive protein levels.

Conclusion. These preliminary data suggest that rHuIL‐1Ra may be safely administered by subcutaneous injection to RA patients. The frequency of dosing appears to be important in determining clinical response, with daily administration providing the most benefit. A placebo‐controlled trial is in progress to further assess the clinical usefulness and to better define appropriate doses of rHuIL‐1Ra in patients with RA.