Literature DB >> 10381910

Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease.

B E Sands1, S Bank, C A Sninsky, M Robinson, S Katz, J W Singleton, P B Miner, M A Safdi, S Galandiuk, S B Hanauer, G W Varilek, A L Buchman, V D Rodgers, B Salzberg, B Cai, J Loewy, M F DeBruin, H Rogge, M Shapiro, U S Schwertschlag.   

Abstract

BACKGROUND & 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 microgram. 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 rhIL-11 40 microgram. kg-1. wk-1 as 2 or 5 weekly doses and 16 microgram. kg-1. week-1 as 5 weekly doses compared with patients receiving placebo (P < 0.05). Patients receiving 16 microgram. 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 microgram. kg-1. wk-1 given in 2 equal doses.

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Year:  1999        PMID: 10381910     DOI: 10.1016/s0016-5085(99)70550-0

Source DB:  PubMed          Journal:  Gastroenterology        ISSN: 0016-5085            Impact factor:   22.682


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