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Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: A population-based
Mathurin Fumery1, Claire Dupont2, Delphine Ley3
1Amiens University Hospital, Gastroenterology, Amiens, France.
Insights
Anti-tumor necrosis factor (anti-TNF) agents show limited long-term effectiveness in pediatric inflammatory bowel disease (IBD). Approximately 60% of Crohn's disease and 70% of ulcerative colitis patients experience treatment failure within five years, primarily due to loss of response.
Area of Science:
- Gastroenterology
- Immunology
- Pediatric Medicine
Background:
- Anti-tumor necrosis factor (anti-TNF) agents are a primary biologic treatment for inflammatory bowel disease (IBD).
- Long-term population-level effectiveness of anti-TNF therapy in pediatric-onset IBD remains understudied.
Purpose of the Study:
- To evaluate the long-term effectiveness and failure rates of anti-TNF agents in pediatric-onset Crohn's disease (CD) and ulcerative colitis (UC).
- To identify factors associated with anti-TNF failure in this population.
Main Methods:
- Retrospective analysis of pediatric-onset CD and UC patients (diagnosed before age 17) from the EPIMAD registry (1988-2011).
- Cumulative probabilities of anti-TNF failure (primary failure, loss of response [LOR], or intolerance) were assessed.
- Cox regression models were used to investigate factors linked to anti-TNF failure.
Main Results:
- Anti-TNF therapy was used in 48% of CD (n=1007) and 24% of UC (n=337) patients, with a median initiation age of 17.4 years.
- Within 5 years, anti-TNF failure rates were approximately 61.9% for CD and 72.7% for UC.
- Loss of response (LOR) was the predominant reason for discontinuation, accounting for about two-thirds of failures. Female gender and longer disease duration were associated with LOR or intolerance in CD and UC, respectively.
- Adverse events leading to treatment termination occurred in 13.5% of patients; no deaths, cancers, or tuberculosis were observed.
Conclusions:
- Long-term anti-TNF effectiveness is limited in pediatric-onset IBD, with high failure rates within 5 years.
- Loss of response is the primary driver of anti-TNF failure in both CD and UC.
- Further research into optimizing anti-TNF therapy and exploring alternative treatments for pediatric IBD is warranted.
Background:
Anti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD.
Methods:
All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model.
Results:
Among a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1-20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0-59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02-2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30-4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15-0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment.
Conclusion:
In a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.
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