Accelerated infliximab infusion safety and tolerability is non-inferior to standard infusion protocol in inflammatory bowel disease patients - a randomized controlled study

Abstract BACKGROUND & AIM Infliximab is typically given over a standard infusion time of 2 hours, leading to a significant burden in inflammatory bowel disease (IBD) patients. Several retrospective and prospective studies have assessed the safety of accelerated infliximab infusions, but not in a randomized controlled setting. We aimed to determine the safety and cost-effectiveness of an accelerated infliximab infusion of 1 hour, compared to the standard 2 hour infusion. METHODS This open label randomized trial was done at a tertiary IBD center in the United States. Patients with an established diagnosis of IBD receiving maintenance infliximab infusions at one of our centers were eligible for inclusion. We excluded patients with a history of infusion reactions and those with known antidrug antibodies to infliximab. Patients were randomly assigned (1:1) to the 1 hour infusion (study) and 2 hour infusion (control) groups using an independent computerized randomization system. The primary outcome was to assess the rate of infusion reactions in the standard 2 hour compared to the accelerated 1 hour study groups. Secondary outcomes were assessment of the effect of pre-medications and concomitant immunomodulators on the rate of infusion reactions, and cost effectiveness analysis. Sample size calculation was based on an infusion reaction rate of 3%, as suggested by recent studies. In order to show a non-inferiority of the accelerated infusion time assuming an infusion reaction rate of 3% while allowing for a 4% non-inferiority limit, a total of 538 infusions would be needed. This would provide a power of 80% and significant alpha of 0.05. Non-inferiority was assessed using Farrington-Manning score test. This trial is registered with ClinicalTrials.gov, NCT05340764. RESULTS From November 2020 to November 2021, we assessed the eligibility of 448 patients, of whom 352 (78%) were excluded primarily due to infusions being received at an outside institution, or patient refusal. Thus, 96 (22%) patients were randomly assigned: 51 (53%) to the 1 hour infusion study group and 45 (47%) to the 2 hour infusion control group. Over a median time of 1 year, a total of 685 infusions were administered: 309 infusions in the control group, and 376 in the study group. 57 (18%) of 309 infusions in the control group and 45 (12%) of 376 infusions in the study group experienced an infusion reaction. The only infusion reaction experienced was hypotension, all of which were asymptomatic and none required infusion discontinuation. Diphenhydramine was associated with an increased rate of infusion reactions (OR 2.04 [95% CI 1.18 – 3.52], p=0.01). Average costs were estimated to reduce by 37% in the accelerated infusion group. CONCLUSION Accelerated 1 hour infliximab infusions are non-inferior in safety and superior in cost-effectiveness compared to standard 2 hour infusions in IBD patients.