Background: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. Summary: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. Key Messages: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

© 2023 S. Karger AG, Basel

Introduction

Chronic rhinosinusitis (CRS) is a common inflammatory disease of otorhinolaryngology that occurs in up to 12% of the general population all over the world [1]. Sinonasal inflammation results in nasal congestion, nasal discharge, facial pain/pressure, and olfactory disorder [2]. CRS is often accompanied by chronic lower airway disease, which places a substantial economic burden on patients. CRS with nasal polyps (CRSwNP) is a severe phenotype of CRS and accounts for 18% of patients with CRS [3]. Almost 20% CRSwNP patients suffer relapse 12 months after receiving intranasal corticosteroids or systemic corticosteroids and/or functional endoscopic sinus surgery (FESS) [4]. The recurrence rate rises to 40% and 80% in 18 months and 12 years post-surgery, respectively. CRSwNP patients have poor health-related quality of life (QoL) because of the high recurrent rate and repeated sinus surgery.

CRS can be classified into three endotypes based on the presence of type 1, type 2, or type 3 inflammation [5]. The exploration of disease endotypes and the introduction of novel agents are important advancements. The use of biologics brings brand new insight to the treatment of CRSwNP. The effectiveness of biological agents in improving the prognosis of CRSwNP has been demonstrated in some well-designed randomized controlled trials [3, 6, 7]. However, there was no consensus on the use of biologics for the CRSwNP. Therefore, the objective of this article was to reach a consensus on the biologics in the treatment of CRSwNP.

Methods

The expert consensus was developed by members of the Chinese Rhinopathy Research Cooperation Group. Studies on biologics for CRS, including clinical trials and systematic reviews, were retrieved in Pubmed, Embase, and Web of Science databases in August 2022. The search terms included “dupilumab,” “omalizumab,” “mepolizumab,” “Nucala,” “Xolair,” “Dupixent,” “biologics,” “biological agent,” “biological treatment,” “chronic rhinosinusitis,” “chronic sinusitis,” “nasal polyp,” and “nasal polyposis.” This article summarized the current literature and proposed consensus recommendations rather than guidelines written with specific levels of evidence. The group members participated in the literature retrieval, article writing, and scrutiny of the consensus statement. Two rounds of discussion and revision of the specific consensus recommendations were conducted in September 2022. The final version of the manuscript was approved by the Chinese Rhinopathy Research Cooperation Group. All recommendations of the consensus are shown in Table 1.

Table 1.

Consensus recommendations on biologics for the management of chronic rhinosinusitis

ItemRecommendation1Biologics are recommended to be administered in CRSwNP patients who have undergone surgical treatment and meet 3 of the following conditions: 1) Evidence of type 2 inflammation; 2) need for systemic corticosteroids or contraindication to systemic steroids; 3) significantly affected the QoL; 4) significant anosmia; 5) comorbid asthma, with needing regular inhaled corticosteroids2Biologics are recommended to be administered in CRSwNP patients who have not received surgery and meet 4 of the following conditions: 1) evidence of type 2 inflammation; 2) need for systemic corticosteroids or contraindication to systemic steroids; 3) significantly affected the QoL; 4) significant anosmia; 5) comorbid asthma, with needing regular inhaled corticosteroids3Biologics are recommended for managing uncontrolled severe type-2 CRSwNP and comorbid asthma or N-ERD, but NOT for acute exacerbations of asthma or acute asthma symptoms4The expert consensus recommends dupilumab, omalizumab, and mepolizumab to CRSwNP patients who meet the indications5It is NOT recommended to use biological agents in CRSsNP.6The consensus suggests omalizumab is more appropriate for patients with elevated IgE levels, while dupilumab and mepolizumab are for patients with significant type 2 inflammation7The recommended dosage of dupilumab for CRSwNP adult patients is 300 mg initially, followed by 300 mg given every other week8It is recommended to administer 100 mg mepolizumab subcutaneously to CRSwNP patients once every 4 weeks9For omalizumab, the recommended dosage is 75 mg–600 mg subcutaneously every 2 or 4 weeks based on body weight and serum total IgE level before the beginning of treatment10It is recommended to discontinue the biological agent without any improvement of olfaction, NCS, NPS, SNOT-22, and VAS total symptoms after 6 months of standard biological treatment. The use of another biological agent, systemic steroids, or surgery would be more recommended11The biological treatment could be continued for 12 months if the olfaction, NCS, NPS, SNOT-22, and VAS total symptoms of CRSwNP patients improve12The biologics could be continued if all of the following conditions are met after 12 months of the initial administration: NPS <4 (total of both sides); NCS <2; VAS total symptoms <5; SNOT-22 score <30. Otherwise, another biological agent or surgery should be considered13It is recommended to utilize the NCS, AQLQ, HRQOL, NPS, VAS, and psychophysical tests for olfaction as clinical efficacy assessment tools14Omalizumab is recommended to be administered with monitoring serum IgE levels. The dosage of prescribed omalizumab is based on total IgE measurement prior to treatment. Serum total IgE testing is recommended beyond 1 year of discontinuation of the drug15The consensus recommends follow-ups after 8 weeks, 16 weeks, 6 months, and 12 months of the first administration of biological agents16For patients on dupilumab and mepolizumab, the consensus does not recommend testing for serum IgE at follow-upIndications of Biological Therapy

EPOS 2020 proposes that CRSwNP patients who have undergone surgical treatment meet 3 of the following conditions or those who have not received surgery meet 4 of the following conditions, biologics therapy can be selected: (1) evidence of type 2 inflammation, tissue eosinophils ≥10/hpf, or blood eosinophils ≥250, or total IgE ≥100; (2) need for systemic corticosteroids or contraindication to systemic steroids, ≥2 courses per year, or long-term (>3 months) low-dose steroids; (3) significantly affected QoL, 22-item Sinonasal Outcome Test (SNOT-22) ≥ 40 points; (4) significant loss of smell; (5) comorbid asthma, with needing regular inhaled corticosteroids [1].

Biological agents are recommended for managing uncontrolled severe type-2 CRSwNP and comorbid asthma or NSAID-exacerbated respiratory disease, but not for acute exacerbations of asthma or acute asthma symptoms. Physicians need to adequately inform patients of the risks of using biologics [4, 8].

Recommended Biologics

Up to now, dupilumab, omalizumab, and mepolizumab are main three biologics approved by US Food and Drug Administration, shown in Table 2. Clinical trials of these recommended monoclonal antibodies for CRSwNP have been presented in Tables 3Table 4.–5, respectively.

Table 2.

Main three biologics approved by FDA

NameApproval yearTargetDupliumab2019IL-4RAOmalizumab2020IgEMepolizumab2021IL-5Table 3.

Main clinical trials of dupliumab

Clinical trialsInclusion criteriaNumber of subjectsEfficacy assessmentTimeDoseFrequencyRoute of administrationBachert et al., 2016 [9]1. The minimum score of bilateral nasal polyps was 5 (at least 2 in each nostril), and INCS treatment was performed at least 8 weeks before enrollment
2. At least 2 of the following symptoms were present before enrollment: nasal congestion; nasal discharge (anterior/posterior rhinorrhea); facial pain/tenderness; hyposmia or loss of smell
3. The study had a prespecified enrollment goal of 50% of patients having a history of asthma (based on patient history)60 (actually completed 51, control group: experimental group = 23:28)The study had a prespecified enrollment goal of 50% of patients having a history of asthma (based on patient history)36 weeksThe study had a prespecified enrollment goal of 50% of patients having a history of asthma (based on patient history)Once a week for 15 weeksSubcutaneous injectionLiberty Sinus 24 [10]1. Aged >18 years old
2. CRSwNP patients
3. Has received systemic glucocorticoid therapy in the past 2 years (or has contraindications or intolerance to systemic glucocorticoids), has a history of nasal polyp surgery, or both
4. Nasal polyp score was not less than 5 (out of 8), and the score of each nasal cavity was not less than 2
5. Symptoms had persisted for at least 8 weeks prior to study entry, including moderate or severe nasal congestion (score 2 or 3) with a weekly mean severity score of at least 1 (range 0–3); there is also at least one of the following other symptoms: hyposmia, anosmia, or anterior and posterior rhinorrhea
6. Patients with concomitant asthma must remain stable during the first 6 weeks of conventional asthma therapy276 (actually completed 262, control group: experimental group 124:138)SNOT-22 score, symptom VAS score, number of patients requiring surgery, endoscopic score, CT score, ED-5Q score, nasopharyngitis24 weeks300 mgEvery 2 weeks for 24 weeksSubcutaneous injectionLiberty Sinus 52 [11]1. Aged ≥18 years old
2. CRSwNP
3. Received systemic corticosteroid therapy within the past 2 years (or with contraindications or intolerance to systemic corticosteroids), previous nasal polyp surgery, or both
4. Endoscopic bilateral nasal polyps score not less than 5 points (total score 8 points), each nasal cavity score not less than 2 points
5. Sustained symptoms for at least 8 weeks prior to study entry, including: moderate or severe nasal obstruction (score 2 or 3) with a weekly mean nasal obstruction severity score of at least 1 (range 0–3); at least one of the following other symptoms: hyposmia, anosmia, or anterior and posterior rhinorrhea
6. Patients with concomitant asthma must be stable for the first 6 weeks on conventional asthma therapy448 (actually completed 428; control group: experimental group = 140: 142 group A: 146 group B)SNOT-22 score, symptom VAS score, number of patients requiring surgery, endoscopic score, CT score, ED-5Q score, nasopharyngitis52 weeks300 mgGroup A: 300 mg every 2 weeks for 24 weeks, then every 4 weeks until week 52
Group B: 300 mg every 2 weeks for 52 weeksSubcutaneous injectionTable 4.

Main clinical trials of omalizumab

Clinical trialsInclusion criteriaSubjectsEfficacy assessmentTimeDoseFrequencyRoute of administrationPinto et al., 2010 [11]1) Age: 18–75
2) CRS symptoms for more than 12 weeks
3) Nasal endoscopy and sinus CT scan with signs of inflammation
4) Total sIgE: 30–700 IU/mL
5) Include CRS without polyps14Imaging of sinus inflammation after 6 months of treatment6 months0.016 mg/kg/(IU/mL)
(Total sIgE)1 time/4 weekssubcutaneous injectionGevaert et al., 2013 [12]1) Age >18 years old
2) Concurrent asthma >2 years
3) Total sIgE: 30–700 IU/mL24 (23 cases completed; control group: experimental group = 8: 23)Nasal polyps score (NPS) decreased (LM score, AQLQ) significantly improved), endoscopic score, CT score16 weeksBased on total sIgE (IU/mL) and body weight (kg), the maximum dose is 375 mg1 time/2 weeks, 8 times in total
1 time/month, 4 times in totalSubcutaneous injectionGevaert et al., 2019 [13]1) Age: 18–75
2) Persistent bilateral nasal polyps, nasal congestion, impaired HRQOL
3) Total sIgE: 30–1,500 IU/mL
4) Weight: 30–150 kg
5) FESS surgery within 6 months should be excluded
6) Those with other lung diseases (excluding asthma) should be excludedPOLYP 1: 138 (133 cases completed; control group: experimental group = 64:69)
POLYP 2: 127 (completed 121 cases; control group: experimental group = 63:58)NPS, NCS, SNOT-22, UPSIT, TNSS, AQLQ24 weeks75–600 mgQ2W or Q4Wsubcutaneous InjectionTable 5.

Main clinical trials of mepolizumab

Clinical trialsInclusion criteriaSubjectsEfficacy assessmentTimeDoseFrequencyRoute of administrationGevaert et al., 2011 [12]1. Chronic sinusitis with primary nasal polyps of grade 3–4 (each nostril score 0–4, higher = worse) or recurrent nasal polyps after surgery (grade 1–4)
2. Chronic nasal – standard treatment for sinusitis and nasal polyp after failure30 (actually completed 10, control group: experimental group = 1:9)Symptom VAS score, endoscopic score, CT score48 weeks750 mgQ4W, 8 weeks in totalSubcutaneous injectionBachert et al., 2017 [13]1. Severe bilateral nasal polyps were diagnosed before enrollment and met the definition of need for surgery (endoscopic nasal polyps score of 3 or more, VAS symptom score greater than 7)
2. Having had at least one nasal polypectomy
3. Not sensitive to steroid therapy, considered potentially eligible for surgery, received at least 3 months of routine/continuous courses of nasal corticosteroids for nasal polyps in the past and/or received short-term oral steroids for nasal polyps
4. Men or women between the ages of 18 and 70
5. BMI in the range of 19.0–31.0 kg/m2 (inclusive)
6. There is no clinical major disease that affects the research plan or endangers its safety
7. Concurrent asthma must be maintained at a dose not exceeding 10 mg/day of prednisolone or equivalent
8. Proper contraception107 (actually completed 74, control group: experimental group = 32:42)SNOT-22 score, symptom VAS score, endoscopic score, EQ-5D QoL score, and need for surgical treatment24 weeks750 mgQ4W, 6 times in totalSubcutaneous injectionSYNAPSE
2021 [14]1. Age: 18 years and older
2. Persistent bilateral nasal polyps (diagnosed by endoscopy or CT scan)
3. Total sIgE: 30–1,500 IU/mL
4. Weight: ≥40 kg
5. Having had at least one previous surgery in the previous 10 years for the removal of nasal polyps414 (actually completed 407, control group: experimental group = 201:206)NPS, Nasal Obstruction VAS score, SNOT-22, overall VAS score, composite VAS score, and individual VAS symptom score52 weeks100 mgQ4Wsubcutaneous injectionSelection and Application of Biological Agents

Based on previous clinical evidence, the expert consensus recommends dupilumab, omalizumab, and mepolizumab to CRSwNP patients who meet the indications. There is little evidence to recommend the use of biologics in CRSsNP. In addition, this consensus suggests omalizumab is more appropriate for patients with elevated IgE levels, while dupilumab and mepolizumab are for patients with significant type 2 inflammation. Dupilumab has the prominent advantage of improving QoL and reducing the risk of comorbid asthma in CRSwNP. In a network meta-analysis, nine clinical trials with 1,190 participants were included and dupilumab performed best in improving outcomes in patients with CRSwNP, followed by omalizumab and mepolizumab [15]. In another network meta-analysis, Cai et al. [16] included seven randomized controlled trials involving 1,913 patients and also found that dupilumab has exhibited better efficacy and safety in the treatment of CRSwNP when compared with omalizumab, mepolizumab, and benralizumab. The basic characteristics of the biologics are shown in Table 6.

Table 6.

The basic characteristics of dupilumab, omalizumab, and mepolizumab

BiologicsProduct nameIndicationsContraindicationRoute of administrationDoseAdverse reactionsDupliumab [17, 18]DUPIXENTAs an add-on maintenance treatment in adult patients with inadequately controlled CRSwNPHypersensitivity to dupilumab or any excipients in DUPIXENTSubcutaneous injectionRecommended dosage for adult patients is 300 mg given every other week (Q2W)Injection site reactions, eosinophilia, insomnia, toothache, gastritis, arthralgia, and conjunctivitisOmalizumab [15, 19]XOLAIRAdult patients aged 18 years and older with inadequate response to nasal corticosteroids, as add-on maintenance treatmentSevere hypersensitivity reaction to XOLAIR or any excipients in XOLAIRSubcutaneous injection75–600 mg every 2 or 4 weeks. Determine dose (mg) and dosing frequency by serum total IgE level (IU/mL)The most common adverse reactions (≥3% of patients) in clinical studies with adult patients included the following: headache, injection site reaction, arthralgia, upper abdominal pain, and dizzinessMepolizumab [16, 20]NUCALAAs an add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP for whom therapy with systemic corticosteroids and/or surgery do not provide adequate disease controlHypersensitivity to the active substance or to any excipients in NUCALASubcutaneous injectionThe recommended dose of mepolizumab is 100 mg administered subcutaneously once every 4 weeksHypersensitivity to the active substance or to any of the excipients listed in sectionThe Use of Biological Agents

The dose, frequency, and duration of treatment vary from one biological agent to another. The recommended dosage of dupilumab for CRSwNP adult patients is 300 mg initially, followed by 300 mg given every other week [21, 22]. It is recommended to administer 100 mg mepolizumab subcutaneously to CRSwNP patients once every 4 weeks [18, 19]. For omalizumab, the recommended dosage is 75 mg–600 mg subcutaneously every 2 or 4 weeks based on body weight and serum total IgE level before the beginning of treatment [17, 23].

As for treatment duration, the patient’s need for biological therapy should be periodically evaluated in accordance with the disease severity and extent of symptom control. When improved QoL (more than double minimal clinically important difference on SNOT-22) and/or ≥50% reduction in systemic corticosteroid use (without further surgery) are observed, it is worth continuing the administration of biological agents [20]. A recent study has shown a significant benefit of prolonging the use of omalizumab to 52 weeks in patients with CRSwNP who have had an inadequate response to nasal corticosteroids, with a high safety profile [24]. However, optimal dose and duration of therapy of omalizumab have not been yet clear [25].

In the EUFOREA paper, discontinuing the current biological agent is required after 6 months of treatment without at least one of the following symptoms or scores: (1) smell score increase ≥0.5 from smell loss to hyposmia or normal sense of smell; (2) nasal congestion score: decrease by ≥0.5 or objective testing; (3) nasal polyp score: decrease by ≥1 by nasal endoscopy; (4) SNOT-22: reduction of ≥8.9; (5) visual analog scale (VAS) total symptoms: reduction of ≥2 cm. If the above improvements can be observed and are acceptable to the patient, it is recommended to continue with biologic treatment, otherwise surgery or systemic glucocorticosteroid need to be considered [26]. After 12 months of treatment, nasal polyp scores, nasal congestion scores, total VAS symptoms, and SNOT-22 scores still need to be followed to decide whether to continue with biologics or switch to other medications or surgery [26]. In EPOS 2020, assessment of treatment response is performed after 16 weeks and 1 year of treatment, which includes: nasal polyp size, need for systemic corticosteroids, QoL, olfaction, and impact of comorbidities. It is recommended to discontinue treatment if no treatment response in any of the criteria is observed [1]. The biologics could be continued if all of the following conditions are met after 12 months of the initial administration: nasal polyp score (NPS) <4 (total of both sides); nasal congestion score (NCS) <2; VAS total symptoms <5; SNOT-22 score <30. Otherwise, another biological agent or surgery should be considered [1].

As an anti-IgE treatment, omalizumab should be administered with monitoring serum IgE levels. The dosage of prescribed omalizumab is based on total IgE measurement prior to treatment [23]. Discontinuation of omalizumab treatment usually results in a return to high levels of free IgE levels and a relapse of the associated symptoms. Total IgE levels are elevated during treatment and remained high within 1 year of treatment discontinuation. Therefore, the dose of omalizumab should not be redetermined based on the remeasured IgE levels during treatment. When treatment is interrupted for less than 1 year, the dose should be determined based on the serum IgE level measured at the time of the first dose determination. Only when treatment has been interrupted for 1 year or more should the dose be determined based on the remeasured total serum IgE level [17].

Efficacy Assessment

Asthma quality of life questionnaire (AQLQ), health-related quality of life (HRQOL), NCS, NPS, and VAS are all commonly used clinical efficacy assessment tools. NCS reflects the extent of nasal blockage severity (scale 0–3) [10]. Bronchial asthma often coexists in CRS and nearly two-thirds of patients with CRS are affected by comorbid asthma [27]. Therefore, the AQLQ, a 32-question instrument, is widely used to measure QoL in CRS adults with comorbid asthma [28, 29].

HRQOL is a collective term for a series of assessment instruments that reflect a patient’s QoL, rather than a single quality-of-life scale. EPOS 2020 steering group agrees that QOL instrument is of importance for the management of CRS [1]. Short Form-36 Health Survey (SF-36) and SNOT-22 are by far the most prevalent HRQOLs. SF-36 reflects the perceived general health status, covering eight domains: physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems and mental health [30]. The SNOT-22, a derivative of the SNOT-20, is a 22-item scale for assessing QoL in patients with CRS in terms of primary or secondary nasal symptoms, sleep-related symptoms and emotional outcomes, compensating for the lack of attention to sinonasal symptoms in SF-36 [31].

Nasal endoscopy and imaging can be quantified by the Lund-Kennedy endoscopic score and the Lund-Mackay score, respectively. Scores for polyposis, mucosal edema, secretions, scarring and the total score (except crusting) are assessed in the Lund-Kennedy endoscopic score [32]. The disease control of CRS can be visualized by comparing the scores before and after treatment. The endoscopic NPS or total polyp score (TPS) is also assessed by observing the polyp size and position under nasal endoscopy (scale 0–8) [33]. The Lund-Mackay CT score is an assessment of the imaging findings of the sinonasal region and helps reflect the inflammatory changes in the nasal sinuses and nasal cavity [34].

The VAS is a practical tool that provides a rough assessment of symptom severity, including nasal congestion, nasal discharge, postnasal drip, facial pain/pressure, and sense of smell [35]. It is simple for patients and clinicians to use without training [35]. However, the EPOS 2020 steering group does not consider self-reported olfactory function results to be reliable enough and believes that accurate assessment of olfactory symptoms should be conducted with psychophysical tests [1]. The most common psychophysical method to assess the sense of smell in patients with CRS is the University of Pennsylvania Smell Identification Test (UPSIT), with a maximum of 40 points score (≤18 points: anosmia; 19–34 points: hyposmia/microsmia; >34 points: normosmia), which allows an accurate assessment of post-treatment efficacy in patients with CRS [36, 37]. Sniffin’ sticks test, including threshold test, discrimination test, and identification test, is also used extensively in Europe and is also a reliable tool for the accurate measurement of olfactory improvement [38].

Prognosis and Follow-Up

The consensus recommends follow-ups after 8 weeks, 16 weeks, 6 months, and 12 months of the first administration of biological agents, helping observe the response to treatment to determine whether to continue using biologics [1, 26]. Subjective scales, nasal endoscopy, and imaging are proper tools to assess treatment effects during a follow-up [33]. The scales include the SNOT-22 and the Patient-Reported Outcome Measure for Chronic Rhinosinusitis (CRS-PRO) [31, 39]; the Lund-Kennedy endoscopic score and NPS can quantify the endoscopic manifestations of lesions; the Lund-Mackay score is used for imaging evaluation. For patients on omalizumab, serum total IgE testing is recommended beyond 1 year of discontinuation of the drug, as serum IgE levels may be persistently elevated for up to 1 year even omalizumab is discontinued and are of little use in guiding dose determination. For patients on dupilumab and mepolizumab, the consensus does not recommend testing for serum IgE at follow-up [17].

Adverse Effects of Biological Agents

Most patients tolerate biological agents well in general with few major or severe adverse effects [26, 40]. There were no significant differences in adverse effects among dupilumab, omalizumab, and mepolizumab in a network meta-analysis [41]. A Cochrane review of biologics for CRS showed that for severe CRSwNP patients with taking intranasal corticosteroid sprays, 24 weeks of dupilumab treatment had no more severe adverse effects than participants taking placebo. Analogous results were observed in patients using omalizumab, but the results could not be fully determined because of the limited participants involved in the included studies [42]. However, some studies [2] have found that omalizumab has shown increased treatment-related adverse events, thereby making conditional recommendations to severe CRSwNP patients rather than strong recommendations.

Among the CRSwNP population with adverse effects to dupilumab, women and the elderly are at higher risk of developing adverse events, while male patients are more likely to have severe adverse events [43]. In addition to injection site reaction, nasopharyngitis, headaches, epistaxis, hypereosinophilia, ophthalmic complications, head and neck dermatitis, alopecia areata, and arthritis are occasionally seen during the use of dupilumab [44, 45].

Conclusion

Currently, the short-term costs of biological agents are high- and short-term effectiveness is less than optimal, so more clinical trials are needed to assess the evidence of cost-benefit and prognosis. In addition, CRS without nasal polyp is not suitable for treatment with biologics. CRS patients require multiple uses of biologics during treatment, and the COVID-19 pandemic challenge patients’ compliance with the suggestion on standardized use of monoclonal antibodies. Despite the limitations of biologics, the emerging monoclonal antibodies have without doubt provided new options for severe uncontrolled CRSwNP patients or patients who do not wish to undergo surgery. Biological agents have a wide range of applications in CRS and more novel biologics which block IL-33, IL-7R, or TSLP will be assessed in high-quality clinical trials in the future, providing more options for the treatment of CRS [1, 46].

Acknowledgments

We would like to gratefully acknowledge the support from members of the Chinese Rhinopathy Research Cooperation Group for precious suggestions on this consensus.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was supported by the National Natural Science Foundation of China (Grant No. 82071018; 81670901; 81371074; 82260219; 82101201; 81970864; 81870706), National Natural Science Foundation for Distinguished Young Scholars of China (Grant No. 81725004), Natural Science Foundation of Guangdong Province, China (Grant No. 2022A1515012617), Zhuhai Science and Technology Planning Project (Grant No. ZH22036201210047PWC), Program of Shanghai Academic/Technology Research Leader (Grant No. 19XD4010000), and Major Project of Shanghai Otolaryngology Clinical Center (Grant No. 20MC920200).

Author Contributions

Jun Tang, Yan-li Yang, Rui Xu, Guo-dong Yu, Zhao-hui Shi, and Xin Wei drafted section 1 of the manuscript and drew Table 2. Yu Xu, Guo-lin Tang, Na Sun, Wei Liao, and Gui Yang drafted section 2 of the manuscript and drew Table 1. You-jin Li, Jing Ye, Ke-jun Zuo, Li-qiang Zhang, Xue-yan Wang, An-ni Yang, and Ying-xiang Xu drafted section 3 of the manuscript and drew Table 3. Hui-ping Ye, Ya-nan Sun, Shao-qing Yu, Tian-hong Zhang, Jun Yong, Wei Hang, and Yuan-teng Xu drafted sections 4–5 of the manuscript and drew Table 4. Hai-yu Hong, Teng-yu Chen, and Qin-tai Yang provided an equal leading role in drafting sections 6–7 of the manuscript. Yue-qi Sun, Feng-hong Chen, Hong-fei Lou, Hong-tian Wang, Rui-li Yu, Zhi-hai Xie, and Yun-fang drafted section 8 of the manuscript and drew Table 5. Feng Liu, Tian-sheng Wang, Mei-ping Lu, Qian-hui Qiu, Xiang-dong Wang, Jian-jun Chen, and Cui-da Meng drafted section 9 of the manuscript. Juan Meng, Ming Zeng, Cheng-li Xu, Ying Wang, Yu-cheng Yang, and Wei-tian Zhang drafted section 10 and drew Table 6. Teng-yu Chen, An-ni Yang, Ying-xiang Xu, Qin-tai Yang, and Hai-yu Hong participated in literature searching. Hai-yu Hong, Yun-ping Fan, and Hua-bin Li revised the manuscript and approved the final version of the manuscript to be published.

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