Interleukin‐2 diphtheria fusion protein (dab486il‐2) in refractory rheumatoid arthritis a double‐blind, placebo‐controlled trial with open‐label extension

Academic Article

Abstract

  • Objective. This pilot phase II, double‐blind, placebo‐controlled trial of 1 month duration, with a 2–3‐month open‐label extension, evaluated the safety, tolerability, biologic effects, and efficacy of interleukin‐2 diphtheria fusion protein (DAB486IL‐2) in refractory rheumatoid arthritis (RA). Methods. Forty‐five RA patients were enrolled in the trial, and were randomized, after a 3–4‐week diseasemodifying antirheumatic drug washout, to receive a daily intravenous dose of either DAB486‐IL‐2 or placebo (saline) for 5 days. A blinded, third‐party observer evaluated arthritis activity. Clinical response was defined as ≥25% improvement in swollen and tender joints and ≥25% improvement in at least 2 of 6 additional parameters. The double‐blind phase was 4 weeks; placebo patients could cross over to receive open‐label treatment for a maximum of 3 monthly DAB486IL‐2 cycles. Results. In the double‐blind phase, 4 of 22 patients (18%) in the treated group and none in the placebo group (P = 0.05) met the criteria for clinical response. During the open‐label treatment phase, 11 of 36 patients (31%) and 11 of 33 patients (33%) had a clinical response after completing 2 and 3 courses of DAB486IL‐2, respectively. Adverse events included transient fever/chills (45%), nause/vomiting (50%), elevated (≥13x normal) transaminases (55%), and increased joint pain (45%). Twelve patients (8 placebo, 4 DAB486IL‐2) did not complete 3 treatment cycles. No apparent differences were noted in CD4+ CD25+ cells of responders versus nonresponders, or of DAB486IL‐2‐treated versus placebo‐treated patients. Conclusion. Clinical responses were noted in patients treated with DAB486IL‐2 (18%) compared with placebo (0%) in the double‐blind phase. In the open‐label phase, 33% of patients completing 3 monthly DAB486IL‐2 cycles had improvement in arthritis activity. Further studies of IL‐2 diphtheria fusion proteins are warranted to elucidate factors that may predict clinical response and define mechanism(s) of action. Copyright © 1995 American College of Rheumatology
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    Author List

  • Moreland LW; Sewell KL; Trentham DE; Bucy RP; Sullivan WF; Schrohenloher RE; Shmerling RH; Parker KC; Swartz WG; Woodworth TG
  • Start Page

  • 1177
  • End Page

  • 1186
  • Volume

  • 38
  • Issue

  • 9