Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020;29(4):97-125.
doi: 10.1007/s40629-020-00126-6. Epub 2020 May 12.

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

Askin Gülsen  1   2 , Bettina Wedi  3 , Uta Jappe  1   2
Affiliations
Review

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

Askin Gülsen et al. Allergo J Int. 2020.

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.

Keywords: Adverse drug reaction; Anaphylaxis; Anti-drug antibodies; Biologicals; Infusion reactions.

PubMed Disclaimer

Conflict of interest statement

Conflict of interestA. Gülsen, B. Wedi, and U. Jappe declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Risk assessment of biotechnological substances
Fig. 2
Fig. 2
Synopsis of all reactions to biotechnological substances
Fig. 3
Fig. 3
a A descriptive graph on the incidence of hypersensitivity reactions to biotechnological substances according to the reviewed databases (for references see the description of the respective BS in the text). b A descriptive graph on the incidence of acute infusion reactions to biotechnological substances according to the reviewed databases (for references see the description of the respective BS in the text). c A descriptive graph on the incidence of anaphylaxis to biotechnological substances according to the reviewed databases (for references see the description of the respective BS in the text)
See this image and copyright information in PMC

References

    1. Scherer K, Spoerl D, Bircher AJ. Adverse drug reactions to biologics. J Dtsch Dermatol Ges. 2010;8(6):411–426. - PubMed
    1. Doessegger L, Banholzer ML. Clinical development methodology for infusion-related reactions with monoclonal antibodies. Clin Transl Immunology. 2015;4(7):e39. doi: 10.1038/cti.2015.14. - DOI - PMC - PubMed
    1. Sociedad Española de Reumatología. Informe Anual Biobadaser 2018. Registro Español de acontecimientos adversos de terapia biológica en enfermedades reumáticas. 2018. https://biobadaser.ser.es/docs/2BIOBADASER%20Informe%20Web%202018.pdf. Accessed 5 Aug 2019.
    1. Castro M, Wenzel SE, Bleecker ER, Pizzichini E, Kuna P, Busse WW. Benralizumab, an anti-interleukin 5 receptor α monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med. 2014;2:879–890. doi: 10.1016/S2213-2600(14)70201-2. - DOI - PubMed
    1. US Food and Drug Administration. FDA labels for benralizumab. 2017. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761070Orig1s000S.... Accessed 1 May 2018.