Utilizing Biologics in Drug Desensitization

Abstract

Purpose of review: The purpose of this literature review was to review the latest advancements with biologics in rapid drug desensitization. Our methodology was to highlight both desensitization to biologics themselves and the use of biologics in desensitization to both biologic and nonbiologic drugs.

Recent findings: Biologics are a vast category of drugs that include monoclonal antibodies, nanobodies, modern vaccinations, and even hormones. Desensitization to biologics can be safely performed through standardized procedure. Biomarkers are used both in vitro and in vivo to help identify and classify hypersensitivity reactions. Hypersensitivity reactions to the mRNA vaccinations against SARS-CoV-2 present their own unique challenges to management. There are specific excipients in monoclonal antibodies that are thought to be responsible for many of their hypersensitivity reactions. Certain biologics can even be used to assist in desensitization to other drugs. Rapid drug desensitization is a standardized procedure that may be able to help many patients who have experienced hypersensitivity reactions to biologics and would best be treated with them to continue to receive them. Biologic drugs have opened a new era in medicine for the prevention and treatment of infectious diseases, cancer, and inflammatory diseases. Hypersensitivity reactions to biologics are quite common. This literature review presents the latest advancements in our understanding of hypersensitivity reactions to biologics, how rapid drug desensitization can be used to continue therapy despite history of hypersensitivity, and how biologics themselves can be used to aid in desensitization itself.

Keywords: Biologics; COVID-19 vaccine; Desensitization; Hypersensitivity; Monoclonal antibodies; Nanobodies.

Fig. 1

International Nonproprietary Names (INN) nomenclature for monoclonal antibodies. A The former classification (before November 2021) first required all monoclonal antibodies (MAbs) to carry the suffix -mab unless they were formed by the fusion of a receptor ligand and an Fc segment, where it would carry the suffix -cept. An infix would be included in the middle of the term (-o-, -xi-, -zu-, or -u-) based on how the MAb was produced (murine, chimeric, humanized, or human). A chimeric antibody has foreign amino acids making up the entire V heavy and light chains and is linked to heavy and light C regions of human origin. A humanized antibody has segments of foreign amino acids interspersed with V segments of human amino acids and the V heavy and light domains are linked to heavy and light C regions of human origin. Other infixes exist in the naming convention but have never been used (-e- for hamster, -i- for primate, etc.). B The current classification applies to all MAbs made after November 2021 and classifies them by their complementarity-determining regions (CDRs) and C regions. MAbs with unmodified C regions and identical sets of CDRs that recognize the same epitope of their target have the suffix -tug. This applies no matter the source of the rest of the MAb, even if chimeric or humanized. Full-sized MAbs with engineered amino acid changes in C regions (even the hinge region) and identical sets of CDRs recognizing the same epitope have the suffix -bart. Immunoglobulins that are bispecific and multispecific (having two different sets of CDRs) regardless of shape have the suffix -mig. These MAbs need not be full-sized immunoglobulins; they only need to have CDRs for two different epitopes, including for example BiTEs (bispecific T-engaging antibodies) and BiKEs (bispecific killer cell engagers) shown here, which are sets of V light and heavy chain CDRs directly linked together without an Fc region. Lastly, monospecific fragments of a full-sized immunoglobulin that are lacking a partial or entire C region have the suffix -ment. Examples shown here are a Fab fragment (fragment antigen-binding), a Fab(‘ab’)₂ fragment (immunoglobulin cleaved by pepsin below the hinge region), and a scFv (single-chain variable fragment). The infixes used in the previous classification are no longer a part of the new classification. C Shown for comparison are a nanobody (a.k.a. single domain antibody) and a nanobody linked to a single-chain variable fragment. Abbr: V, variable; C, constant (created, in part, with BioRender.com)

Fig. 2

The seven types of drug reactions and whether rapid drug desensitization is indicated (created, in part, with BioRender.com. From Yang BC, Castells MC. The Who, What, Where, When, Why, and How of Drug Desensitization. Immunology and Allergy Clinics of North America. 2022. https://doi.org/10.1016/j.iac.2021.12.004; with permission)

Fig. 3

Algorithm for risk stratification for intravenous rapid drug desensitization. SCARs, severe cutaneous adverse reactions (toxic epidermal necrolysis, Stevens-Johnson syndrome, drug eruption with eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis) (from Yang BC, Castells MC. Rituximab hypersensitivity and desensitization: a personalized approach to treat cancer and connective tissue diseases. Ann Allergy Asthma Immunol. 2019;123(1):11–5. https://doi.org/10.1016/j.anai.2019.03.008; with permission)

Fig. 4

Premedication for rapid drug desensitization is personalized for each patient and is based on the symptoms of the original reaction (from Yang BC, Castells M. Diagnosis and Treatment of Drug Hypersensitivity Reactions to Biologicals: Medical Algorithm. Allergy. 2020. https://doi.org/10.1111/all.14432; with permission)

Fig. 5

Algorithm for the management of breakthrough reactions during intravenous rapid drug desensitization (from Yang BC, Castells MC. Rituximab hypersensitivity and desensitization: a personalized approach to treat cancer and connective tissue diseases. Ann Allergy Asthma Immunol. 2019;123(1):11–5. https://doi.org/10.1016/j.anai.2019.03.008; with permission)