Comparison of the pharmacokinetics of CT-P13 between Crohn's Disease and Ulcerative Colitis in biologic-naive patients; a prospective multi-center observational study of the KASID

Abstract

Background We aimed to compare trough infliximab levels and the development of anti-drug antibody (ADA) for 1 year between Crohn’s disease (CD) and ulcerative colitis (UC) patients who were biologic-naïve and to evaluate their impact on clinical outcomes.

Methods This was a prospective, multi-center, observational study. Biologic-naïve patients with moderate to severe CD and UC who started CT-P13 therapy were eligible for the study. The trough drug and ADA levels were measured serially for 1-year after CT-P13 initiation. Clinical outcomes were assessed with intention-to-treat purpose.

Results 267 patients who received CT-P13 treatment were enrolled in the study (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, p<0.001) and clinical response (75.6% vs. 47.5%, p<0.001) at 54-week were significantly higher in CD than in UC. The median trough drug level (μg/mL) was significantly higher in CD than in UC up to 14-week (2-week, 19 vs. 15, p<0.001; 6-week, 13 vs. 9, p<0.001; 14-week, 3 vs. 2, p=0.001, Fig 1). The median ADA level (AU/mL) was significantly lower in CD than in UC at 2-week (6 vs. 7, p=0.046), 30-week (8 vs. 12, p=0.007) and 54-week (9 vs. 12, p=0.032, Fig 1). The difference in drug and ADA levels between CD and UC remained significant after adjustment for confounders in repeated measures analysis. Cox proportional hazard analysis showed that CD over UC (adjusted hazard ratio (aHR) 0.78, 95% confidence interval (CI) 0.62–0.95, p=0.016, Fig 2) and no immunomodulator (aHR 1.55, 95% CI 1.07–2.25, p=0.02) were independent risk factors for the development of ADA. The development of ADA at 2-week (adjusted odds ratio (aOR) 0.12, 95% CI 0.03–0.6, p=0.009) and CD over UC (aOR 1.85, 95% CI 1.33–2.56, p=0.0002) were independent predictors of clinical remission at 54-week.

graphic graphic Conclusion CD shows favorable pharmacokinetics of infliximab including high trough drug and low ADA level compared with UC which might be related with better clinical outcomes for 1-year of infliximab.