Clinical trial: a multicentre, randomized, double-blind, placebo-controlled, dose-finding, phase II study of subcutaneous interferon-beta-la in moderately active ulcerative colitis.
BACKGROUND
Ulcerative colitis (UC) pathophysiology is characterized by an imbalance between pro- and anti-inflammatory cytokines. Interferon (IFN)-beta-1a has potent immunoregulatory properties, including stimulation of host defence mechanisms and thus represents a potential treatment.


OBJECTIVE
To extend pilot data and identify a suitable dose of IFN-beta-1a to achieve endoscopically confirmed remission (ECR) in patients with moderately active UC and to evaluate safety.


METHODS
In this multicentre, double-blind, placebo-controlled trial, adults with moderately active UC were randomized to IFN-beta-1a 44 or 66 microg, or placebo, subcutaneously three times weekly for 8 weeks, with a 4-week follow-up.


RESULTS
Endoscopically-confirmed remission was observed in 23.4% [95% confidence interval (CI): 13.8-35.7] of placebo patients, 29.2% (95% CI: 18.6-41.8) of the IFN-beta-la 44 microg group and 20.0% (950% CI: 11.1-31.8) of the 66 microg group (P = 0.45). Improvements with IFN-beta-1a 44 microg were greater than with placebo for most secondary efficacy outcomes, although significance was not achieved. Placebo response rates were higher than expected from previous trials. Adverse events were similar to the known safety profile of IFN treatment.


CONCLUSIONS
Interferon-beta-1a was generally well tolerated at the doses tested, but a significant therapeutic benefit in patients with UC was not observed.
Pena-Rossi
C
C
New Therapies, Merck Serono International S.A., Geneva, Switzerland. claudia.penarossi@merckserono.net
Schreiber
S
S
Golubovic
G
G
Mertz-Nielsen
A
A
Panes
J
J
Rachmilewitz
D
D
Shieh
M J
MJ
Simanenkov
V I
VI
Stanton
D
D
Graffner
H
H
D000328:Adult; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D016099:Endoscopy, Gastrointestinal; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D010919:Placebos; D011788:Quality of Life; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome
D007155:Immunologic Factors; D010919:Placebos; D016899:Interferon-beta