Etanercept-induced injection site reactions: potential pathomechanisms and clinical assessment

Etanercept (ETN) is a tumor necrosis factor alpha (TNF-α) antagonist used for the treatment of chronic inflammatory disorders. Injection site reactions (ISRs) are reported to be the most common adverse event of ETN therapy. While their mechanisms are not completely understood, the occurrence of ETN-ISRs could indicate a risk of systemic immune-mediated severe adverse drug reactions.

Based on two cases and a review of the literature, the characteristics and frequency of ETN-ISRs were assessed. This article discusses their potential mechanisms and clinical relevance, and provides recommendations for the management of patients presenting with ETN-ISRs.

Basically, irritative and immune-mediated ISRs may be distinguished. The formation of anti-drug antibodies (ADAs) may promote immune-mediated ISRs that likely represent either anaphylactic type I reactions, or cutaneous Arthus-like type III reactions according to the Coombs and Gell classification. A differentiation between these reactions by clinical course and etanercept-skin testing may help to decide if ETN treatment should be stopped to avoid the development of more severe adverse drug reactions if ISRs occur.