Background and Aims: Recombinant human interleukin 11 (rhIL-11) is a cytokine with thrombocytopoietic activity and anti-inflammatory and mucosal protective effects. The objectives of this study were to investigate the safety and tolerability of rhIL-11 in patients with Crohn's disease and to explore the effects of dose and schedule on platelet count and Crohn's disease activity. Methods: A multicenter, double-masked, placebo-controlled, dose-escalation study of 76 patients with active Crohn's disease was performed. Patients were randomized to receive subcutaneous placebo or rhIL- 11 at doses of 5, 16, or 40 μg · kg-1 · wk-1 given 2 or 5 times weekly for 3 weeks. Clinical and laboratory safety data were recorded, and disease activity was measured at each visit. Results: Subcutaneous injection of rhIL- 11 generally was well tolerated. Significantly greater increases in platelet counts were found among patients receiving rhlL-11 40 μg · kg-1 · wk- 1 as 2 or 5 weekly doses and 16 μg · kg-1 · week-1 as 5 weekly doses compared with patients receiving placebo (P ≤ 0.05). Patients receiving 16 μg · kg-1 · wk-1 had the highest clinical response rates, with a response seen in 42% of patients (5/12) receiving 5 weekly doses and 33% of patients (4/12) receiving 2 weekly doses, compared with 7% of patients (1/15) receiving placebo. Conclusions: Short-term treatment with rhIL-11 is well tolerated in patients with active Crohn's disease. The thrombocytopoietic effect of rhIL-11 seems to be both dose and schedule dependent and may be minimized with retained clinical benefit in Crohn's disease at 16 μg · kg- 1 μ wk-1 given in 2 equal doses.
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