Infliximab dependency in children with Crohn's disease.
BACKGROUND
Recently, infliximab dependency has been described.


OBJECTIVE
To assess frequency of ID in 82 consecutive Crohn's disease children treated with infliximab 2000-2006 and to describe clinical and genetic predictors of long-term infliximab response.


METHODS
A phenotype model of infliximab dependency was used to assess treatment response: 'immediate outcome' (30 days after infliximab start)--complete/partial/no response. 'Long-term outcome': (i) prolonged response: maintenance of complete/partial response; (ii) infliximab dependency: relapse < or = 90 days after intended infliximab cessation requiring repeated infusions to regain complete/partial response or need of infliximab >12 months to sustain response. Polymorphisms TNF-308 A>G, TNF-857 C>T, Casp9 93 C>T, FasL-844 C>T, LTA 252 C>T and CARD15 (R702W, G908R, 1007fs) were analysed.


RESULTS
Ninety-four per cent of children obtained complete/partial response. In long-term outcome, 22% maintained prolonged response, 12% had no response, while 66% became infliximab dependent. Perianal disease and no previous surgery were associated with infliximab dependency (OR 5.34, 95% CI: 1.24-22.55; OR 6.7, 95% CI: 1.67-26.61). No association was found with studied polymorphisms. The cumulative probability of surgery 50 months after starting infliximab was 10% in infliximab dependency, 30% in prolonged responders and 70% in nonresponders (P = 0.0002).


CONCLUSIONS
Sixty-six per cent of children became infliximab dependent. Perianal disease and no surgery prior to infliximab were associated with infliximab dependency phenotype.
Duricova
D
D
4th Department of Internal Medicine, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
Pedersen
N
N
Lenicek
M
M
Hradsky
O
O
Bronsky
J
J
Adamcova
M
M
Elkjaer
M
M
Andersen
P S
PS
Vitek
L
L
Larsen
K
K
Lukas
M
M
Nevoral
J
J
Wewer
V
V
Munkholm
P
P
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D000069285:Infliximab; D008297:Male; D010641:Phenotype; D012074:Remission Induction; D012189:Retrospective Studies; D019966:Substance-Related Disorders / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D000069285:Infliximab