According to the 2022 practice parameter update from the American Academy of Allergy, Asthma, and Immunology (AAAAI), although excipients rarely cause immediate or delayed drug reactions, some, like propylene glycol (PEG), are associated with delayed responses. The most concerning reactions involve life-threatening anaphylaxis linked to excipients like PEG and carboxymethylcellulose, especially in injectable corticosteroids. The cross-reactivity of polysorbates with PEG necessitates further research for optimal testing strategies. An excipient allergy may be considered in patients with a history of anaphylaxis to more than two structurally unrelated drugs or products sharing a common excipient, such as PEG-based laxatives or injectable corticosteroids. [1]
While not specific to certolizumab, a 2016 review explored the increasing incidence of immediate-type hypersensitivity reactions to polyethylene glycols (PEGs), also known as macrogols. The authors found that PEGs, common excipients in medications, bowel preparations, medical materials, and household products, were frequently overlooked as culprits, leading to repeated severe reactions prior to diagnosis. Most anaphylactic events followed oral or parenteral exposure, particularly to high-molecular-weight PEGs (e.g., PEG 3350, 4000, 6000), and many patients reacted to multiple PEG molecular weights and, in some cases, to structurally related polymers such as polysorbates. Skin testing often demonstrated reproducible immediate-type responses, though risk of systemic reactions required cautious titration. While PEG-specific IgE has not been directly identified, basophil activation and inhibition studies provided supportive evidence for an IgE-mediated mechanism. Overall, the review highlights that PEG hypersensitivity, though rare, is severe, underrecognized, and associated with cross-reactivity across PEGs, PEG-derivatives, and PEGylated drugs, underscoring the need for heightened clinical awareness and careful evaluation of excipients in patients with unexplained or recurrent immediate hypersensitivity reactions. [2]
Another review article focuses on hypersensitivity to PEG, citing the prominent case report by McCabe et al. (Table 1), in which a 37-year-old woman with psoriatic arthritis experienced anaphylaxis after being administered certolizumab pegol. Due to the patient’s history of allergic reactions to other agents containing PEG, this ingredient was suspected of being the most likely trigger for anaphylaxis. Still, allergies specific to PEG are considered to be rare, but severe immediate hypersensitivity reactions have been described in the literature. [3]