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.

Guidelines for medical treatment of acute Kawasaki disease: Report of the Research Committee of the Japanese Society of Pediatric Cardiology and Cardiac Surgery (2012 revised version)

“…As for long‐term IFX treatment, in a study of 163 patients with JIA (68 receiving IFX and 95 receiving etanercept; mean age, 17 years; mean treatment period, 22.9 months), there were 71 adverse events, and 62.9% of the events occurred in patients treated with IFX. In contrast, another report found IFX to be safe and well‐tolerated, with few side‐effects . Among patients with JIA who had been receiving IFX for 1 year, the incidence of infusion reaction was 3.3% among those who had been receiving a dose of 3 mg/kg and 7% among those receiving 6 mg/kg .…”

“…In contrast, another report found IFX to be safe and well-tolerated, with few side-effects. 73 Among patients with JIA who had been receiving IFX for 1 year, the incidence of infusion reaction was 3.3% among those who had been receiving a dose of 3 mg/kg and 7% among those receiving 6 mg/kg. 74,75 In addition, neutralizing human antichimeric antibodies (HACA) were found in many patients who developed an infusionassociated reaction.…”

“…Adverse events were reported in 28% of these patients within 6 months of first use; 6.2% of these were severe adverse events, including bacterial pneumonia (2.2%, 108 patients), Pneumocystis pneumonia (0.4%, 22 patients), sepsis (0.2%, 10 patients), tuberculosis (0.3%, 14 patients), and severe infusion reaction (0.5%, 24 patients; Table 7). [66][67][68][69][70][71][72][73][74][75][76] As for patients with juvenile idiopathic arthritis (JIA), there is a report that adverse events were more frequent at lower doses (3 mg/kg) than at higher doses (6 mg/kg). 69 There are limited data, however, on the safety of IFX in children.…”

Balancing and Communicating the Risks and Benefits of Biologics in Pediatric Inflammatory Bowel Disease

“…41 Pre-medication with anti-histamines or corticosteroids does not appear to prevent the development of initial infusion reactions in children. 76, 77 Although premedication was not used or commented on routinely throughout the studies, our review suggests that it does appear to possibly prevent repeat reactions in those patients who continue on treatment after an initial AIR and therefore should be considered for patients continuing on therapy. 41 …”

Biologics in Paediatric Crohn's Disease

“…Reintroduction should be considered a second-line approach now that alternative biologics are available. Although patients are often predosed with antihistamines and steroids before infusions, there is relatively little evidence, at least for antihistamines, that these provide significant protection against acute infusion reactions in children [88]. …”