Impact of Obesity on the Outcomes in Patients With Ulcerative Colitis Treated With Advanced Therapies: A Retrospective Cohort Study
Background:
Obesity has been associated with a more severe phenotype of Crohn’s disease (CD), and ulcerative colitis (UC), characterized by decreased rates of corticosteroid-free remission, increased risk for surgery, and shorter intervals between disease flares. This may be due to altered gut microbiota, systemic inflammation, and changes in medication pharmacokinetics. Despite this, limited data exist on the outcomes of these patients with obesity and UC on different advanced therapies.
Methods:
We conducted a retrospective cohort study from the U.S. Collaborative Network in the TriNetX database evaluating adult patients with UC and obesity (BMI ≥30 kg/m<sup>2</sup>), compared to patients with normal BMI (18.5-24.9 kg/m<sup>2</sup>) [control group]. Patients with malnutrition, low BMI (< 18.5 kg/m<sup>2</sup>), or overweight BMI (25-29.9 kg/m<sup>2</sup>) were excluded from the control cohort. Patients were further categorized based on their advanced therapy: TNF inhibitors (TNFi), vedolizumab, ustekinumab, or janus kinase inhibitors (JAKi). One-to-one propensity score matching (PSM) was used to balance covariates based on demographics, comorbid conditions, and IBD medications, including steroid use. The primary outcome was a composite of oral or intravenous corticosteroid use, advanced therapy change, or colectomy at 1, and 2 years. The risk was expressed as an adjusted odds ratio (aOR) with 95% confidence intervals.
Results:
There were 3,904, 2,025, 1,150, and 477 patients on TNFi, vedolizumab, ustekinumab, and JAKi, respectively, in the UC obesity cohort. After PSM, the UC obesity cohort on TNFi had an increased risk of the composite outcome corticosteroid use, advanced therapy change or colectomy at 1-year (aOR 1.64, 95% CI 1.48-1.83), and 2-years (aOR 1.76, 95% CI 1.59-1.96) compared to the control group. There was an increased risk of steroid use (aOR 1.45, 95% CI 1.19-1.40) and colectomy (aOR 1.4, 95% CI 1.09-1.81) in the UC obesity cohort on TNFi. Sub-group analysis based on type of TNFi also showed an increased 2-year risk for both infliximab (aOR 1.74, 95% CI 1.48-2.03), and adalimumab (aOR 1.49, 95% CI 1.26-1.75). The UC obesity cohort had an increased risk of the composite outcome at 1-year on vedolizumab (aOR 1.58, 95% CI 1.35-1.84) and ustekinumab (aOR 1.52, 95% CI 1.13-1.41) and at 2-years on vedolizumab (aOR 1.59, 95% CI 1.36-1.85) and ustekinumab (aOR 1.48, 95% CI 1.21-1.81). Finally, the UC obesity cohort on JAK inhibitors also had an increased risk of the composite outcomes at 1-year (aOR 1.56, 95% CI 1.14-2.15) and 2-years (aOR 1.61, 95% CI 1.17-2.22).
Conclusions:
Our study showed that obesity is associated with worse outcomes in patients with UC treated with advanced therapies. These findings highlight the need to address obesity to improve the efficacy and durability of advanced therapies for this patient population.
