The safety of monoclonal antibodies in asthma

ABSTRACT

Introduction: In the last two decades the knowledge of the mechanisms of the inflammatory processes underlying asthma rapidly evolved, several key mediators (cytokines and receptors) were identified, and the laboratory techniques have allowed us to synthesize monoclonal antibodies highly specific for those target molecules. Nowadays, many biological agents are investigated in asthma (with anti IgE being the only commercially available). The clinical efficacy of some biologics was demonstrated in many cases, however, the safety issue has progressively emerged and has been recognized as a crucial aspect.

Areas covered: We summarized the currently available knowledge on the safety and side effects of biologics in asthma, as derived by reviews, meta analyses and clinical trials. PubMed was searched with the terms anti IL-x [AND] safety [OR] side effects, within the categories “clinical trial”, meta-analysis” and “review”. Case reports were excluded. The authors collegially selected the relevant entries to be included.

Expert opinion: Overall, the safety of most of the investigated agents seems to be satisfactory, a certain risk of side effects remains present, and is variable for the different molecules. Thus caution must be paid in evaluating the risk to benefit ratio. Specific biomarkers to predict the response to each biological are urgently needed to improve the safety profile.

KEYWORDS:

• Asthma
• allergic asthma
• severe asthma
• monoclonal antibody
• cytokine
• safety
• adverse events

Article highlights

• Asthma is a heterogeneous disease. Despite the clinical and functional aspects are common, different phenotypes/endotypes can be recognized. Allergic asthma is the most studied model.

• Several cytokines, cells and receptors are currently recognized as pivotal elements in asthma-related inflammation (IgE, IL-4, IL-5, IL13, IL-17)

• Monoclonal antibodies specific to relevant targets of inflammations are now available, and many of them are undergoing clinical trials.

• For anti IgE (in use since >10 years), there is a large amount of evidence. Efficacy and safety data are available for many of the biological agents from the published clinical trials.

• Biologicals (in particular Monoclonal Antibodies) may exert both favourable and undesired side effects with various mechanisms.

• Non-specific adverse events (headache, local reactions, diarrhea etc.) invariably resulted to be more frequent in active than in placebo groups.

• Overall, the biological agents tested in asthma displayed an overall efficacy to safety favourable profile, but this is not applicable at the same extent to each single agent.

• A ‘precision medicine’ approach, including the search for biomarkers, would be necessary to appropriately prescribe biological agents, maintaining an optimal safety profile.

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Declaration of interest

This work was partly supported by ARMIA (Associazione Ricerca Malattie Immunologiche e Allergiche). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.