Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease.
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.
Sands
B E
BE
Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. bsands@partners.org
Bank
S
S
Sninsky
C A
CA
Robinson
M
M
Katz
S
S
Singleton
J W
JW
Miner
P B
PB
Safdi
M A
MA
Galandiuk
S
S
Hanauer
S B
SB
Varilek
G W
GW
Buchman
A L
AL
Rodgers
V D
VD
Salzberg
B
B
Cai
B
B
Loewy
J
J
DeBruin
M F
MF
Rogge
H
H
Shapiro
M
M
Schwertschlag
U S
US
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
D000906:Antibodies; D017370:Interleukin-11; D011994:Recombinant Proteins