Dose-Intensified Infliximab Rescue Therapy for Severe Ulcerative Colitis Does Not Reduce Short-term Colectomy Rates or Increase Postoperative Complications

Abstract

BACKGROUND: Dose-intensified rescue therapy with infliximab for hospitalized patients with ulcerative colitis has become increasingly popular in recent years. However, there is ongoing debate about both the efficacy of these regimens to reduce the rate of colectomy and the associated risks of increased infliximab exposure. OBJECTIVE: The purpose of this study was to compare the colectomy and postoperative complication rates in hospitalized patients with severe ulcerative colitis receiving standard infliximab induction therapy (3 doses of 5 mg/kg at weeks 0, 2, and 6) and dose-intensified regimens including a higher weight-based dosing or more rapid interval. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted at an academic tertiary care hospital. PATIENTS: A total of 145 adult patients received inpatient rescue infliximab therapy for the treatment of ulcerative colitis between 2008 and 2020. MAIN OUTCOME MEASURES: The primary outcome was colectomy rate within 3 months of rescue therapy. Secondary outcomes include mid-term colectomy rates, as well as perioperative complications in patients receiving colectomy within 3 months of rescue infliximab initiation. RESULTS: The proportion of dose-intensified regimens increased over time. Unadjusted 3-month colectomy rates were 14% in patients who received standard rescue infliximab dosing, 16% in patients given a single dose-escalated dose, and 24% in patients given multiple inpatient dose-escalated doses. These rates were not statistically significantly different. Of the patients requiring colectomy within 3 months of infliximab rescue, those who received multiple inpatient doses of dose-escalated therapy had a higher percentage of colectomy during the initial hospitalization but a lower rate of perioperative complications. LIMITATIONS: This study was limited by the use of retrospective data and the limited power to account for the heterogeneity of disease. CONCLUSIONS: No significant difference was found in colectomy rates between patients receiving standard or dose-intensified regimens. However, dose-intensified regimens, including multiple inpatient doses given to patients with more severe disease, were not associated with a greater risk of perioperative complications. See Video Abstract at http://links.lww.com/DCR/B864. La terapia de rescate con dosis intensificada de infliximab en colitis ulcerosa grave no reduce las tasas de colectomía a corto plazo ni aumenta las complicaciones posoperatorias ANTECEDENTES: La terapia de rescate de dosis intensificada con infliximab para pacientes hospitalizados con colitis ulcerosa se ha vuelto cada vez más popular en los últimos años. Sin embargo, existe un debate en curso sobre la eficacia de estos regímenes para reducir la tasa de colectomía y los riesgos asociados a una mayor exposición al infliximab. OBJETIVO: El propósito de este estudio fue comparar las tasas de colectomía y complicaciones posoperatorias en pacientes hospitalizados con colitis ulcerosa grave que recibieron t...

Dose Escalation Patterns of Advanced Therapies in Crohn’s Disease and Ulcerative Colitis: A Systematic Literature Review

“…Two studies conducted in NA reported an initial maintenance pattern in alignment with FDA label recommendations (5 mg/kg every 8 weeks) in a median of 89% of patients (range 78–100%) [ 124 , 125 , 127 , 173 , 174 ]. Outside of NA, most studies ( N = 8) reported an initial maintenance dose of 5 mg/kg every 8 weeks in a median of 100% of patients (range 68–100%) [ 7 , 123 , 132 , 139 – 143 , 157 , 175 – 179 ].…”

Dose-Intensified Infliximab Rescue Therapy on Short-term Colectomy Rates in Patients With Severe Ulcerative Colitis

“…To the Editor-We read with interest the article by Kosaraju et al comparing the colectomy and postoperative complication rates in hospitalized patients with acute severe ulcerative colitis (ASUC) receiving standard infliximab (IFX) and dose-intensified regimens. 1 The authors found no significant difference in colectomy rates between the 2 groups, but other studies found a lower rate of colectomy in patients with intensified dosing or high-dose IFX. 2 Furthermore, some expert opinions suggest that high-dose IFX induction is now the preferred schedule of administration for IFX induction therapy in ASUC.…”

Reply

“…We thank Drs Dai and Huang for their insightful commentary on our report of infliximab rescue therapy for acute severe ulcerative colitis (ASUC). 1 Dai and Huang highlight that we rely on an imperfect combination of clinical and patient factors to inform treatment and prognosis in ASUC. We agree that much remains unknown about which therapy, including colectomy, is best.…”