Prevention of acute adverse events related to infliximab infusions in pediatric patients

Abstract

Objective. To study whether premedication with an oral antifebrile agent (acetaminophen) and antihistamine (cetirizine) could decrease the frequency of acute infusion reactions in pediatric patients. Methods. All pediatric patients scheduled for infliximab infusions at the Helsinki University Central Hospital, a tertiary care center, were prospectively introduced to a standard oral premedication of acetaminophen (20 mg/kg) and cetirizine (10 mg) prior to infliximab infusions for a period of 1 year. All acute adverse events related to infliximab infusions given according to the guidelines of pediatric rheumatologists or gastroenterologists were registered for this time period and retrospectively during the preceding year. Results. During the study period, infliximab infusions with premedication were given to 64 pediatric patients (48 with rheumatic disease and l6 with inflammatory bowel disease, mean age 13 years, n ‫؍‬ 34 boys, and n ‫؍‬ 30 girls). Infliximab was introduced to 14 children; the rest were on maintenance therapy. Twelve infusion reactions, 4 mild and 8 severe, were observed in 8 (12.5%) of the 64 subjects, and in 1 subject 4 times. During the preceding year, 60 pediatric patients had received infliximab infusions without premedication. In this latter group, infusion reactions occurred in 5 children (8.3%; P > 0.05). The presentation of an acute infusion reaction was not related to the sex or diagnosis of the patient. Conclusion. In pediatric patients, acute infusion reactions related to infliximab could not be prevented with premedication with oral acetaminophen and cetirizine.

Pediatric rheumatology infusion center: report on therapeutic protocols and infusions given over 4 Years with focus on adverse events over 1 Year

“…With respect to dose, the mean infliximab dose was 13.8 mg/Kg, with none of our patients receiving doses < 6 mg/Kg. This appears to reflect a strong difference between our patients and those reported by Lahdenne et al [ 12 ] , in whom the average total dose was 243 mg ; the article by Al-Mayouf et al [ 11 ] did not discuss medication doses or pre-medications. These factors appear to result in decreased incidence of development of anti-drug antibodies and of infusion reactions in general [ 19 , 20 ], and use of anti-metabolites appeared to be protective against the development of infusion reactions among patients taking infliximab in our study; levels of anti-drug antibodies were not routinely available in our patients.…”

“…However, Al-Mayouf et al [ 11 ] reported 10 suspected anaphylaxis reactions, 8 of which were associated with infliximab among 52 patients taking infusions. Likewise, Lahdenne et al [ 12 ] reported 12 infusion reactions, 8 of which were deemed severe, among 64 patients taking infliximab despite 100% use of anti-metabolites. In contrast to these experiences, our experience has been largely positive.…”

“…With respect to infliximab, the role of pre-medication is less clear. A randomized trial indicated that pre-medication with betamethasone provided no benefit [ 15 ], while observational studies have yield mixed evidence with respect to benefits of anti-histamines [ 10 , 12 , 16 , 17 ]. Arguably, however, the rarity (9/816) and mild nature of the infusion reactions among patients taking infliximab provide scant impetus to adjust the protocols.…”

Infliximab in Pediatric Rheumatology Patients: A Retrospective Analysis of Infusion Reactions and Severe Adverse Events During 2246 Infusions over 12 Years

“…Based on our observation, we suggest continuing IFX treatment in case of a mild or moderate IR with the administration of additional premedication (antihistamines and corticosteroids as necessary) and an increase in IFX dose. The beneficial effect of premedication with antihistamines has already been shown by other groups 22 . The risk reduction of anti-drug antibody formation by comedication with an immunosuppressive drug has been shown in different studies 17,28,29 ; there was no difference in the incidence of IR between the different comedication drugs in our patients.…”

Premedication with intravenous steroids does not influence the incidence of infusion reactions following infliximab infusions in pediatric inflammatory bowel disease patients—a case-control study

“…In the pediatric setting, only few studies have addressed this issue, of which most studies were underpowered. Additionally, most of these studies did not distinguish between different types of PM, so no firm conclusions could be drawn [12,13,18]. A recent retrospective study including a larger cohort of pediatric IBD patients also assessed the influence of PM with corticosteroids, antihistamines, and acetaminophen on risk for IR [19].…”