(13) Anti-TNFα, immunomodulators and treatment failure in pediatric and adolescent patients with Crohn’s disease

Författare/Medförfattare

Ken Lund, Michael D. Larsen, Torben Knudsen, Jens Kjeldsen, Rasmus G. Nielsen, Bente M. Nørgård Corresponding Author : Ken Lund, Bsc. PT, Msc.H., PhD-student Center for Clinical Epidemiology, Odense University Hospital. Kloevervaenget 30, Entrance 216. DK-5000 Odense E.: ken.lund@rsyd.dk ORCID: https://orcid.org/0000-0002-3959-2926

Affiliates

Ken Lund[1, 2], Michael D. Larsen[1, 2, 3], Torben Knudsen[4, 5], Jens Kjeldsen[6, 7], Rasmus G. Nielsen[8, 9], Bente M. Nørgård[1, 2] [1] Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark. [2] Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark. [3] Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway [4] Department of Medicine, Hospital of Southwest Jutland, Esbjerg, Denmark. [5] Department of Regional Health Science, Center Southwest Jutland, University of Southern Denmark, Esbjerg, Denmark. [6] Department of Medical Gastroenterology S, Odense University Hospital, Odense, Denmark. [7] Research Unit of Medical Gastroenterology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark. [8] Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark. [9] Research Unit of Pediatrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Abstrakt

Background
The role of combination therapy, anti-TNFα and immunomodulators (thiopurine or methotrexate) versus monotherapy with anti-TNFα is debated, and there is very sparse data to support clinical decision making. Based on nationwide Danish data, we examined whether anti-TNFα therapy combined with immunomodulators, compared to anti-TNFα therapy alone, reduces the possibility of an intestinal surgery or a switch to another anti-TNFα agent within a follow-up period of 24 months.

Methods
We identified all patients with Crohn’s disease, aged ≤20 years at the time of the first anti-TNFα treatment, registered in the Danish National Patient Register. When examining the outcome intestinal surgery we used the study period 1 January 2003 through 31 December 2015. When examining the outcome of a switch to another anti-TNFα agent, we used the study period from 1 January 2007 to 31 December 2015 (adalimumab was not used regularly as an alternative anti-TNFα treatment before). We identified prescriptions of immunomodulators in the Danish National Prescriptions Register. We used Cox regressions models to compare patients with combination therapy to patients with anti-TNFα therapy alone.

Results
We had a study population of 648 pediatric patients for the analyses of surgeries. We identified 8.6% (31/358) having intestinal surgeries in patients with combination therapy within 24 months and 14.1% (41/290) in patients with anti-TNFα alone. The adjusted two-year hazard ratio (HR) of intestinal surgeries was 0.52 (confidence interval (CI) 95%: 0.33-0.86) in patients with combination therapy compared to patients with anti-TNFα alone. We had 602 pediatric patients when examining a switch to another anti-TNFα agent. We identified 18.4% (60/326) with a switch to another TNF-α agent in patients with combination therapy and 25.0% (69/276) in patients with anti-TNFα alone. The adjusted two-year HR of a switch to another anti-TNFα agent was 0.58 (CI 95%: 0.45-0.93).

Conclusions
In children with Crohn’s disease, the two-year risk of intestinal surgeries and the risk of a switch to another anti-TNFα was statistical significantly reduced in those receiving combination therapy, compared to patients only receiving anti-TNFα. These results in pediatric patients with Crohn’s disease speak for the benefit of anti-TNFα therapy combined with immunomodulators.