Infliximab, a monoclonal antibody against tumor necrosis factor alpha, is commonly used as a steroid-sparing agent in patients with both Crohn's disease (CD) and ulcerative colitis (UC). Despite clinical utility, Infliximab is associated with acute infusion reactions, ranging in severity from local skin reactions to anaphylaxis. While the mechanism of action remains unclear, various premedications are often used to prevent these reactions. However, there is limited data to suggest that the use of pre-medications actually prevents infusion reactions. We aimed to determine whether the use of pre-medications is associated with a reduced number of infliximab reactions and if so, which medications were most effective.Methods:
A retrospective chart review was performed for all patients with a diagnosis of CD and UC treated with Infliximab from 2008 to 2016. Demographic information, IBD-specific disease characteristics, details of infliximab infusions including dosage, administration interval, use of premedications and any reactions were collected.Results:
Thousand five hundred ninty-five infliximab infusions were identified amongst 150 subjects with 28 (1.7%) acute infusion reactions in 21 individuals. Baseline characteristics including type of IBD, age, gender, comorbidities such as asthma, eczema, or psoriasis, and presence of drug allergies were not significantly different between subjects that developed a reaction and those that did not (P-value > 0.05). Fifty-three percent (15/28) of infusion reactions occurred during induction dosing (weeks 0, 2, and 6) with an average dose of infliximab of 5.89 mg. 7% (2/28) of reactions occurred in the setting of missed infusions with a delay of 2 weeks; all others were within 8 or 4 weeks of prior treatment. Those that were previously exposed to infliximab were more likely to have infusion reactions (OR = 6.23, 95% CI, 1.72–23.08, P = 0.002). In those with an infusion reaction, 39% (11/28) were premedicated with IV diphenhydramine, 21% (6/28) received prophylactic oral diphenhydramine, 36% (10/28) received IV hydrocortisone (50–100 mg), and 29% (8/28) received IV hydration (250 mL normal saline over 31 min). The use of premedications (any of the ones listed above) did not significantly reduce the number of infusion reactions (P = 0.29). Seventy-one percent (20/28) of reactions occurred with a pre-medication regimen; Paradoxically, when evaluating individual medications, the use of oral diphenhydramine and IV hydrocortisone were associated with an increased numbers of reactions (P = 0.048 and 0.019 respectively).Conclusions:
Premedication use in hopes of preventing an acute infliximab-related infusion reaction is common. However, the administration of premedications seems ineffective in reducing the number of acute infliximab infusion reactions in our population. Prior exposure to infliximab predicted infusion reactions. Use of oral Benadryl and IV hydrocortisone not only did not help prevent reactions, but was instead associated with an increased risk. Perhaps this is because patients who received these medications were at a higher risk for having a reaction and the medications simply did not provide significant protection, begging the question of whether the risk of premedications outweigh the benefit in the setting of outpatient infliximab administration. Larger, prospective clinical trials need to be done to further elucidate this relationship.