Immediate Hypersensitivity Reactions to Biologic Drugs in Children With Inflammatory Bowel Diseases

To assess immediate hypersensitivity reactions (I-HSRs) to biologic drugs (BDs) in pediatric patients with inflammatory bowel disease (IBD), examining frequency, clinical features, management, and associated risk factors.All children diagnosed at Gaza University between January 1, 2006, and August 1, 2023, and who developed I-HSRs related to any BD were included in the study.Study participants met the following criteria: age 0 to 18 years at diagnosis, using at least 1 BD for IBD, and attended regular follow-ups. Participants’ medical records were reviewed for the following data: IBD type, age, gender, age at diagnosis, duration of follow-up, comorbid allergic conditions (atopic dermatitis, food allergy, asthma, allergic rhinitis, drug allergy), nonallergic chronic diseases, family history of allergic disease and IBD, presence of extraintestinal manifestations, and treatment status. Intravenous BD administration occurred in clinic, while subcutaneous BDs were initially administered in the clinic then transitioned to home and no premedication was applied. Any suspicion of HSR was referred to a pediatric allergist. Reactions were classified only if they occurred within 1 to 6 hours of administration or infusion. I-HSRs were then categorized into one of the following groups: type 1 HSR (immunoglobulin E [IgE]/non-IgE) immediate symptoms, cytokine release syndrome (CRS) developing symptoms a few minutes to a few hours later, mixed reaction for type 1 and CRS (overlapping symptoms), and infusion-related reactions (IRRs). Patients who experienced I-HSRs underwent skin testing 4 weeks after reaction. Negative skin prick testing with undiluted forms of the BDs was followed by intradermal testing with dilutions of 1/100 and 1/10. Positive was considered if the wheal was more than 3 mm larger than the negative control.Sixty-one patients met study criteria including the use of a BD. Thirteen patients had 16 different comorbid allergic diseases. Four different BD were administered to the 61 patients, for a total of 1679 exposures. Fourteen received 2 different BDs, and 1 received 3 different BDs. I-HSRs developed in 6 patients, resulting in a frequency of 9.8% per patient and 0.36% per administration. Of the 6 total, 4 developed type 1, and 2 developed an IRR. All reactions were mild or moderate; no severe reactions were observed. One patient was able to receive infliximab 17 times through a rapid desensitization program. Two patients who developed an IRR were able to tolerate subsequent dosing with infusions at the proper rate. Two were changed to ustekinumab after refusing rapid desensitization. Overall, a statistically significant difference was found between allergic and nonallergic patients, 33% vs 5.8%, with a P value of 0.037.The frequency of I-HSRs to BD in children with IBD is not rare but is not likely to be severe. If patients have comorbid allergic disease, this has shown to be a risk factor in the development of I-HSRs. HSRs are less likely to fully human or humanized BD, such as adalimumab, due to eliciting a lower immunogenic response. Vedolizumab and ustekinumab had zero I-HSRs, likely due to humanized nature, but also lower numbers of patients using.Risk of reactions should not deter BD use in IBD, as severe reactions are unlikely. Allergic comorbidities increase risk and should factor in determining appropriate BD and if additional monitoring for administration is required. Further study is needed due to limited study size and additional BD being used.