Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events*

Abstract

Purpose: Biotechnological substances (BSs) are strongly relied upon to prevent rejection of transplanted organs, and to treat oncological, allergological, and other inflammatory diseases. Allergic reactions to partly foreign biologics can occur due to their potential immunogenicity. The severity of an immune response to a biological drug may range from no clinical significance to a severe, life-threatening anaphylactic reaction. Methods: Detailed searches were performed on Pubmed, Web of Science, and Google Scholar to include all available publications. In addition, the Food and Drug Administration, the European Medicines Agency, and British Columbia Cancer Agency Drug Manual databases were screened for hypersensitivity reaction (HSR), infusion reaction, injection site reaction, urticaria, and anaphylaxis for individual BSs. Results: Treatment with BSs can cause various types of HSR. These are mentioned in the literature with definitions such as allergic reactions, anaphylactoid reactions, anaphylaxis, HSR, infusion reactions, injection site reactions, cytokine release syndrome, and urticaria. Due to the overlap in signs and symptoms in the reported descriptions, it is not always possible to differentiate these reactions properly according to their pathomechanism. Similarly, many data reported as anaphylaxis actually describe severe anaphylactic reactions (grades III or IV). Conclusion: There is an urgent need for a simpler symptom-or system-based classification and scoring system to create an awareness for HSRs to BSs. A better understanding of the pathophysiology of HSRs and increased clinical experience in the treatment of side effects will provide timely control of unexpected reactions. As a result, immunotherapy with BSs will become safer in the future. Cite this as Gülsen A, Wedi B, Jappe U. Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events.

Atezolizumab-induced anaphylactic shock in a patient with hepatocellular carcinoma undergoing immunotherapy: A case report

“…In the European Medicines Agency 2019 assessment report, HSRs of atezolizumab were reported in in up to 10% of patients[ 11 ]. In addition, pruritis and rash were reported in more than 10% of patients[ 6 ]. According to the recent BC Cancer Agency Drug Manual, HSRs including anaphylaxis can be severe in < 1% of the patients, and immune-mediated rash may appear in 8%-18% (severe, 1%) of patients[ 10 ].…”

“…Atezolizumab is a humanized immunoglobulin (Ig)G-1 class antibody that binds to PD-L1 approved by the Food and Drug Administration (FDA) for the treatment of cancer[ 5 ]. The FDA reported severe IRs in 1.3%-1.7% and HSRs in ≤ 1% of cases in which atezolizumab was used[ 6 ]. However, cases of atezolizumab-associated anaphylactic shock are rare.…”

Adalimumab-Induced Thrombocytopenia in a Patient With Hidradenitis Suppurativa

“…The drug acts by inhibiting the binding of TNF-alpha to p55 and p75 receptors located on the surface of target cells. Like the other anti-TNF-alpha agents, adalimumab is used for the treatment of inflammatory conditions such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis [ 5 , 6 ]. In addition, adalimumab is the only drug approved by the FDA for the treatment of moderate-to-severe hidradenitis suppurativa, a chronic, relapsing, inflammatory disorder characterized by the presence of painful nodules, abscesses, sinus tracks, and scarring mainly in the inguinal and axillary regions [ 7 , 8 ].…”

Biologics for atopic diseases: Indication, side effect management, and new developments

“…However, a comprehensive review of databases and scientific literature has shown that, on the one hand, the nomenclature of hypersensitivity reactions to biologicals is not harmonized, so that data on the prevalence and incidence of “real” allergic and anaphylactic reactions to the various biologicals cannot be reliably collected [ 88 , 89 ]. Furthermore, the symptomatology of anaphylaxis may vary between different biologicals [ 87 ].…”