Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group.
OBJECTIVE
Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties. We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn's disease (CD).


METHODS
A prospective, multicenter, double-blind, placebo-controlled study was conducted in 329 therapy-refractory patients with CD. Clinical improvement was defined by a reduction of the Crohn's Disease Activity Index (CDAI) by 100 points or more and clinical remission by a decrease of the CDAI to <150 points. At selected centers, patients underwent ileocolonoscopies and activation of the nuclear factor-kappa B (NF-kappa B) system was assessed in biopsy specimens.


RESULTS
Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible, dose-dependent decrease in hemoglobin and thrombocyte counts but no clinically significant side effects. No differences in the induction of remission were observed between rhuIL-10 groups (1 microg, 18% [9.6-29.2]; 4 microg, 20% [11.3-32.2]; 8 microg, 20% [11.1-31.8]; 20 microg, 28% [18-40.7]; and placebo, 18% [9.6-29.6]). Clinical improvement was observed in 46% (33.7-59) in the 8-microg/kg rhuIL-10 group in comparison with 27% (17-39.6) in patients taking placebo. Responders to rhuIL-10 showed inhibition of NF-kappaB p65 activation in contrast to nonresponders.


CONCLUSIONS
Up to 8 microg/kg of rhuIL-10 was well tolerated. A tendency toward clinical improvement but not remission was observed in the 8-microg/kg dose group. Further studies should delineate which subgroups of patients with CD benefit from rhuIL-10 therapy.
Schreiber
S
S
Charité University Hospital, Fourth Medical Department, Humboldt University, Berlin, Germany. s.schreiber@mucosa.de
Fedorak
R N
RN
Nielsen
O H
OH
Wild
G
G
Williams
C N
CN
Nikolaus
S
S
Jacyna
M
M
Lashner
B A
BA
Gangl
A
A
Rutgeerts
P
P
Isaacs
K
K
van Deventer
S J
SJ
Koningsberger
J C
JC
Cohard
M
M
LeBeaut
A
A
Hanauer
S B
SB
D000328:Adult; D002908:Chronic Disease; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004351:Drug Resistance; D016145:Endoscopy, Digestive System; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000502:physiology; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D010352:Patient Dropouts; D011446:Prospective Studies; D011788:Quality of Life; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012074:Remission Induction; D019233:Retreatment; D012449:Safety; D012720:Severity of Illness Index; D013256:Steroids / Q000627:therapeutic use; D016896:Treatment Outcome
D020672:I-kappa B Proteins; D011994:Recombinant Proteins; D013256:Steroids; D016753:Interleukin-10