C0395 - Treatment Failure and Clinical Response Differences in Fixed-Dosing versus Weight-Adjusted Anti-TNF Therapy in Obese Patients With Ulcerative Colitis

Trevor Schell, MD, Alexander Lee, MD, Christopher R. Lindholm, MD, Zhanhai Li, PhD, Emmanuel Sampene, PhD, Sumonha Saha, MD, MS
University of Wisconsin School of Medicine and Public Health, Madison, WI

Introduction: Obesity (BMI >30 kg/m²) in patients with ulcerative colitis (UC) is associated with an increased risk of treatment failure, hospitalization, and surgery. Pharmacokinetic studies of biologic therapies used to treat inflammatory bowel disease (IBD) have shown that higher BMI is associated with increased clearance and lower drug concentrations. Direct comparisons between fixed-dosing and weight-adjusted anti-tumor necrosis factor (anti-TNF) therapies are limited. We aimed to compare the rate of treatment failure and clinical response of fixed-dosing adalimumab (ADA) versus weight-based infliximab (IFX) in obese patients with UC.

Methods: This was a single-center, retrospective cohort study of obese patients aged 18–75 years old with UC who initiated treatment with fixed-dosing ADA or weight-based IFX, per standard induction and maintenance dosing regimens, from January 2015 – December 2020. Patient characteristics including sex, age, BMI, disease duration and extent, serologic markers of inflammation, and concurrent medications were extracted from the electronic health record. Disease severity before and after anti-TNF therapy was assessed using the physician global assessment (PGA) score (0–3, 0=normal, 3=severe disease) based on clinical status during clinic visits, endoscopic Mayo scores and histologic disease severity. The primary outcome was rate of treatment failure (i.e., lack of clinical response, need for colectomy, or change in biologic therapy).

Results: Eighty-nine patients were identified (Table 1). The rate of treatment failure was greater in those on ADA than IFX, although without statistical significance (53% vs 34%, p=0.079). Based on PGA score, those treated with IFX were more likely to have clinical improvement than ADA (-1.55 ± 0.95 vs -0.59 ± 0.92, p< 0.001) (Figure 1). Using multivariate logistic regression analysis, ADA was associated with an increased risk of treatment failure (OR 3.02, p=0.03).

Discussion: We found that fixed-dosing ADA, compared to weight-based IFX, appears to be associated with worse clinical outcomes and higher risk of treatment failure in obese patients with UC. Due to the pharmacokinetics of increased drug clearance seen with greater BMI, weight-based dosing regimens of anti-TNF therapies may be more effective in such patients. Prospective studies with drug level testing are needed to further evaluate the impact of obesity on treatment response to anti-TNF therapies in IBD.




Disclosures:


Trevor Schell, MD, Alexander Lee, MD, Christopher R. Lindholm, MD, Zhanhai Li, PhD, Emmanuel Sampene, PhD, Sumonha Saha, MD, MS. C0395 - Treatment Failure and Clinical Response Differences in Fixed-Dosing versus Weight-Adjusted Anti-TNF Therapy in Obese Patients With Ulcerative Colitis, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.