Dose-range and dose-frequency study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis. The IL-1Ra Arthritis Study Group

Arthritis Rheum. 1996 Jul;39(7):1092-101. doi: 10.1002/art.1780390704.


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 rHulL-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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / blood
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / therapy*
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Injections, Subcutaneous
  • Interleukin 1 Receptor Antagonist Protein
  • Male
  • Middle Aged
  • Quality of Life
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Receptors, Interleukin-1 / immunology
  • Recombinant Proteins / administration & dosage*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / immunology
  • Severity of Illness Index*
  • Sialoglycoproteins / adverse effects
  • Sialoglycoproteins / immunology
  • Sialoglycoproteins / therapeutic use*
  • Treatment Outcome


  • Antibodies
  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Sialoglycoproteins