Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial.
BACKGROUND
Ciclosporin and infliximab are potential rescue treatments to avoid colectomy in patients with acute severe ulcerative colitis refractory to intravenous corticosteroids. We compared the efficacy and safety of these drugs for this indication.


METHODS
In this parallel, open-label, randomised controlled trial, patients were aged at least 18 years, had an acute severe flare of ulcerative colitis defined by a Lichtiger score greater than 10 points, and had been given an unsuccessful course of high-dose intravenous steroids. None of the patients had previously received ciclosporin or infliximab. Between June 1, 2007, and Aug 31, 2010, patients at 27 European centres were randomly assigned (via computer-derived permutation tables; 1:1) to receive either intravenous ciclosporin (2 mg/kg per day for 1 week, followed by oral drug until day 98) or infliximab (5 mg/kg on days 0, 14, and 42). In both groups, azathioprine was started at day 7 in patients with a clinical response. Neither patients nor investigators were masked to study treatment. The primary efficacy outcome was treatment failure defined by absence of a clinical response at day 7, a relapse between day 7 and day 98, absence of steroid-free remission at day 98, a severe adverse event leading to treatment interruption, colectomy, or death. Analysis was by intention to treat. This trial is registered with EudraCT (2006-005299-42) and ClinicalTrials.gov (NCT00542152).


RESULTS
115 patients were randomly assigned; 58 patients were allocated to receive ciclosporin and 57 to receive infliximab. Treatment failure occurred in 35 (60%) patients given ciclosporin and 31 (54%) given infliximab (absolute risk difference 6%; 95% CI -7 to 19; p=0·52). Nine (16%) patients in the ciclosporin group and 14 (25%) in the infliximab group had severe adverse events.


CONCLUSIONS
Ciclosporin was not more effective than infliximab in patients with acute severe ulcerative colitis refractory to intravenous steroids. In clinical practice, treatment choice should be guided by physician and centre experience.


BACKGROUND
Association François Aupetit, Société Nationale Française de Gastroentérologie, and the International Organization for the study of Inflammatory Bowel Disease.
CHU de Bordeaux, Hôpital Haut-Lévêque, Service d'Hépato-Gastroentérologie, Bordeaux, France. david.laharie@chu-bordeaux.fr
David
D
Laharie
Arnaud
A
Bourreille
Julien
J
Branche
Matthieu
M
Allez
Yoram
Y
Bouhnik
Jerome
J
Filippi
Frank
F
Zerbib
Guillaume
G
Savoye
Maria
M
Nachury
Jacques
J
Moreau
Jean-Charles
JC
Delchier
Jacques
J
Cosnes
Elena
E
Ricart
Olivier
O
Dewit
Antonio
A
Lopez-Sanroman
Jean-Louis
JL
Dupas
Franck
F
Carbonnel
Gilles
G
Bommelaer
Benoit
B
Coffin
Xavier
X
Roblin
Gert
G
Van Assche
Maria
M
Esteve
Martti
M
Färkkilä
Javier P
JP
Gisbert
Philippe
P
Marteau
Stephane
S
Nahon
Martine
M
de Vos
Denis
D
Franchimont
Jean-Yves
JY
Mary
Jean-Frederic
JF
Colombel
Marc
M
Lémann
D000208:Acute Disease; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D016572:Cyclosporine / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D013256:Steroids / Q000008:administration & dosage*; D017211:Treatment Failure
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D013256:Steroids; D016572:Cyclosporine; D000069285:Infliximab