Among pediatric patients with acute severe ulcerative colitis (ASUC), infliximab (IFX) clearance predicted clinical outcomes, according to study results published in Clinical Gastroenterology and Hepatology.
The Anti-TNF Therapy for Refractory Colitis in Hospitalized Children (ARCH) study (ClinicalTrials.gov Identifier: NCT02799615) was a prospective cohort study conducted in the United States and Canada between 2016 and 2018. Children (N=38) with ASUC or unclassified inflammatory bowel disease were given IFX. Predictors of clinical response at day 7, defined as a pediatric ulcerative colitis activity index (PUCAI) score of less than 35 were evaluated.
The study population included children with a median age of 14.5 (IQR, 13.3-16.8) years, 50% were girls, 84% were White, 89% were receiving concomitant steroids, and PUCAI score was 75 (IQR, 70-80) at baseline.
The median dose of IFX was 9.9 mg/kg, and 89% received a dose greater than 7 mg/kg. Approximately two-thirds of patients maintained a dosing interval of less than or equal to 6 weeks.
At day 7, the clinical response rate was 71.1%. At week 8, 55.3% were in clinical remission, and at week 26, 43.2% had corticosteroid-free clinical remission. Treatment was stopped before 26 weeks among 21.6%. Of those, 1 patient underwent colectomy, 1 was switched to adalimumab due to reaction, and 6 were switched to vedolizumab due to nonresponse.
Faster IFX clearance was associated with IFX antibodies, higher white blood cell count, and lower albumin.
Stratified by response, median IFX exposure on day 7 was numerically but not significantly higher among nonresponders compared with responders. Clearance of IFX was significantly higher on day 7 than at week 8 (P =.002) or week 26 (P <.001), indicating that IFX clearance slows with exposure. In addition, clearance was significantly faster among nonremitters than remitters (P =.011).
Response at day 7 associated with lower PUCAI score at day 3 with an area under the receiver operating characteristic curve of 0.747 (P =.033). Lower PUCAI score at day 7 associated with remission at week 26 (P =.021). A PUCAI cutoff of less than or equal to 15 predicted remission at week 26 with a sensitivity of 75.0%, specificity of 71.4%, positive predictive value of 66.7%, and negative predictive value of 78.9%.
Risk for colectomy associated with rapid IFX clearance at day 3 (hazard ratio [HR], 1.302; 95% CI, 1.068-1.588). Clearance greater than 0.02 L/h associated with colectomy risk (HR, 58.2; 95% CI, 6.0-568.6; P <.001).
The major limitation of this study was the lack of standardized dosing.
“IFX clearance is associated with colectomy and CSF-CR in pediatric ASUC,” the study authors noted. “In this contemporary cohort treated with higher than standard IFX dosing, we observed a lower colectomy rate than that reported previously. Initial 10 mg/kg dosing may be sufficient to overcome rapid drug clearance and optimize early outcomes in pediatric ASUC; however, further investigation is warranted to determine if sustained intensification of maintenance regimens can improve longer term outcomes.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Whaley KG, Xiong Y, Karns R, et al. Multicenter cohort study of infliximab pharmacokinetics and therapy response in pediatric acute severe ulcerative colitis. Clin Gastroenterol Hepatol. Published online August 28, 2022. doi:10.1016/j.cgh.2022.08.016