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Clinical and Experimental Otorhinolaryngology > Volume 15(2); 2022 > Article
Kim and Yang: Application of Biologics in Treating Chronic Rhinosinusitis With Nasal Polyps in Asian Populations
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a relatively common inflammatory disorder, diagnosed when nasal obstruction or rhinorrhea lasts for more than 12 weeks and signs of inflammation are identified via nasal endoscopy or computed tomography [1]. The pathophysiology of CRSwNP has been studied and elucidated over the past two decades via in vitro experiments and analyses of cytokines in nasal tissues from patients. The role of type 2 inflammation was brought to light, as the severity of type 2 inflammation is related to comorbid lower respiratory tract diseases, such as asthma, and the severe form of chronic rhinosinusitis accompanied by nasal polyps [2].
New therapeutic strategies, such as biologics or reboot surgery, were introduced as a response to treat the recalcitrant nature of severe type 2 CRSwNP, which often shows a poor response to traditional treatment. The prevalence of type 2 inflammation in CRSwNP and severe type 2 inflammation related to severe infiltration of eosinophils and neutrophils with staphylococcal enterotoxin-specific immunoglobulin E in Asian population is below 50% and 4.4%–11.2%, respectively [3], much lower than in Western populations [4]. In addition, a study proposed that the response of type 2 CRSwNP to surgery is very much different from that of non-type 2 CRSwNP [5], and as a result, the role of biologics in treating CRSwNP in Asian populations seemed to be limited.
However, the use of dupilumab and omalizumab, which were recently approved for the treatment of CRSwNP in South Korea, has led to some interesting findings. Postoperative steroid-dependent anosmia, independent of disease severity, is one of many symptoms in type 2 CRSwNP patients and is an unresolved problem even in Asian populations with a relatively low prevalence of type 2 CRSwNP. Olfactory dysfunction greatly diminishes patients’ quality of life and is not well controlled with surgical treatment [6]. In such patients, the postoperative use of a systemic corticosteroid in a repetitive manner may result in a variety of adverse drug reactions, prompting a need to switch to biologics. Interestingly, patients with olfactory dysfunction usually have low disease burden, as the extent of the nasal polyp or disease entity is often limited to the olfactory cleft. As a result, such patients respond well to biologics, as the first couple of doses can dramatically slow down nasal polyp formation and improve olfaction.
Monoclonal antibodies are usually eliminated by proteolytic catabolism, because their size exceeds the glomerular filtration cut-off threshold, and their distribution is limited to vascular and interstitial spaces due to their large size and hydrophilicity [7]. Considering that monoclonal antibodies are eliminated partly via target-mediated clearance, the number of target molecules in patients with a low disease burden is presumably small, which also means that extending the dosing interval can result in the maintenance of a certain degree of therapeutic effects. A randomized, double-blind phase 3 trial of dupilumab demonstrated that there was no statistically significant difference in efficacy between a group of patients treated with dupilumab every 2 weeks for 52 weeks and another group of patients treated with dupilumab every 2 weeks for 24 weeks and every 4 weeks for the remaining 28 weeks [8]. This result suggests the possibility of extending dosing intervals in CRSwNP patients after lowering the disease burden to a certain degree. In fact, there have been attempts at adjusting dosing intervals for conditions other than CRSwNP [9].
In summary, establishing a dosing strategy based on patients’ disease burden can certainly result in an individualized approach in treating CRSwNP with biologics, which would provide substantial benefits for Asians with CRSwNP, who tend to show low disease burden and mild to moderate type 2 inflammation, and would contribute to securing the cost-effectiveness of biologics for CRSwNP treatment.

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

Notes

AUTHOR CONTRIBUTIONS

Conceptualization: DWK. Data curation: DWK. Formal analysis: DWK. Methodology: DWK. Project administration: DWK. Writing–original draft: DWK. Writing–review & editing: SKY.

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