Long-term durability of infliximab treatment in Crohn's disease and efficacy of dose "escalation" in patients losing response.
BACKGROUND
The efficacy of infliximab therapy in patients with Crohn's disease (CD) is unknown beyond 12 months. For patients who lose their initial response, consideration can be given to dose "escalation" to regain therapeutic benefit.


OBJECTIVE
Our primary goal was to evaluate the long-term durability of maintenance infliximab treatment. The secondary goals were to identify potential predictors of loss of infliximab efficacy, to evaluate the response to infliximab escalation, and the safety of the treatment with infliximab with and without escalation of dose.


METHODS
CD patients treated with infliximab with response to an induction regimen were evaluated. Maintenance of long-term response was estimated using Kaplan-Meier analysis. The effect of specific variables was calculated using logistic regression analysis. Efficacy of dose escalation in patients who lose response to infliximab was analyzed.


RESULTS
Three hundred and nine CD patients were included. The mean follow-up time with infliximab treatment was 41 months, and the majority (95%) were on concomitant immunosuppressive therapy. The annual risk of loss of response to infliximab was 12% per patient-year of treatment. After loss of response, 41% of patients were managed with infliximab therapy escalation. After the first intensified dose, 56% of patients achieved remission and 40% partial response. Concurrent immunomodulators enhanced and smoking decreased the proportion of patients who maintained response (P<0.05).


CONCLUSIONS
A relevant proportion of CD patients on long-term infliximab treatment loss response. After loss of response, a high proportion of these patients initially respond to infliximab dose escalation. Concurrent immunomodulators may increase and smoking may decrease maintenance of response.
Gastroenterology Unit of Hospital La Princesa, Madrid, Spain. mariachs2005@gmail.com
María
M
Chaparro
Julián
J
Panes
Valle
V
García
Miriam
M
Mañosa
María
M
Esteve
Olga
O
Merino
Montserrat
M
Andreu
Ana
A
Gutierrez
Fernando
F
Gomollón
José Luis
JL
Cabriada
Miguel Angel
MA
Montoro
Juan Luis
JL
Mendoza
Pilar
P
Nos
Javier P
JP
Gisbert
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003424:Crohn Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D000069285:Infliximab