title: Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. bsands@partners.org
authors.forename: B E
authors.initials: BE
authors.lastname: Sands
authors.forename: S
authors.initials: S
authors.lastname: Bank
authors.forename: C A
authors.initials: CA
authors.lastname: Sninsky
authors.forename: M
authors.initials: M
authors.lastname: Robinson
authors.forename: S
authors.initials: S
authors.lastname: Katz
authors.forename: J W
authors.initials: JW
authors.lastname: Singleton
authors.forename: P B
authors.initials: PB
authors.lastname: Miner
authors.forename: M A
authors.initials: MA
authors.lastname: Safdi
authors.forename: S
authors.initials: S
authors.lastname: Galandiuk
authors.forename: S B
authors.initials: SB
authors.lastname: Hanauer
authors.forename: G W
authors.initials: GW
authors.lastname: Varilek
authors.forename: A L
authors.initials: AL
authors.lastname: Buchman
authors.forename: V D
authors.initials: VD
authors.lastname: Rodgers
authors.forename: B
authors.initials: B
authors.lastname: Salzberg
authors.forename: B
authors.initials: B
authors.lastname: Cai
authors.forename: J
authors.initials: J
authors.lastname: Loewy
authors.forename: M F
authors.initials: MF
authors.lastname: DeBruin
authors.forename: H
authors.initials: H
authors.lastname: Rogge
authors.forename: M
authors.initials: M
authors.lastname: Shapiro
authors.forename: U S
authors.initials: US
authors.lastname: Schwertschlag
mesh_terms: D000328:Adult; D000906:Antibodies / Q000032:analysis; D003424:Crohn Disease / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D017370:Interleukin-11 / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins
chemical_list: D000906:Antibodies; D017370:Interleukin-11; D011994:Recombinant Proteins