Infliximab, Immunomodulators and Treatment Failures in Paediatric and Adolescent Patients with Crohn's Disease: a Nationwide Cohort Study.
BACKGROUND AND AIMS
In paediatric patients with Crohn's disease, the role of combination therapy, infliximab plus immunomodulators [thiopurine or methotrexate], is debated and data are sparse. We examined whether infliximab plus immunomodulators, compared to infliximab therapy alone, reduces the risk of treatment failure measured by intestinal surgery or switching type of anti-tumour necrosis factor [TNF] α agent within 24 months.


DESIGN
Using Danish registries, we identified patients with Crohn's disease, aged ≤ 20 years at the time of the first infliximab treatment, and retrieved data on their co-medications. We used Cox regression models to examine surgery or switching type of anti-TNFα agent from January 1, 2003 to December 31, 2015.


RESULTS
We included 581 patients. The 2-year cumulative percentage of surgery was 8.5% among patients receiving combination therapy and 14.5% in those receiving infliximab alone. The adjusted 2-year hazard ratio [HR] of surgeries was 0.53 (95% confidence interval [CI] 0.32-0.88) in patients receiving combination therapy, compared to patients receiving infliximab alone. When examining a switch of anti-TNFα we included 536 patients. Within 2 years, 18.3% experienced a switch among patients receiving combination therapy and 24.8% in patients treated with infliximab alone, corresponding to an adjusted HR of 0.66 [95% CI 0.45-0.97] in patients receiving combination therapy.


CONCLUSIONS
The HR of intestinal surgeries and the risk of a switch to another anti-TNFα was reduced in paediatric and adolescent patients receiving combination therapy, compared to patients receiving only infliximab. These results suggest a benefit for infliximab therapy combined with immunomodulators, but these need to be confirmed in data with additional clinical information.
['Lund|Ken|K|', 'Larsen|Michael Due|MD|', 'Knudsen|Torben|T|', 'Kjeldsen|Jens|J|', 'Nielsen|Rasmus Gaardskær|RG|', 'Mertz Nørgård|Bente|B|']
D000068879:Adalimumab D000293:Adolescent D001379:Azathioprine D002648:Child D003424:Crohn Disease D003718:Denmark D004359:Drug Therapy, Combination D005260:Female D005765:Gastrointestinal Agents D006801:Humans D007155:Immunologic Factors D000069285:Infliximab D008297:Male D015122:Mercaptopurine D008727:Methotrexate D017211:Treatment Failure D014409:Tumor Necrosis Factor-alpha D055815:Young Adult
infliximab immunomodulators paediatrics adolescents Crohn’s disease