Introduction
In the United States and Europe, chronic rhinosinusitis (CRS) is a widespread disorder affecting roughly 10 to 13 per cent of the adult demographic. Its polyp-associated variant (CRS with nasal polyps [CRSwNP]) is estimated to occur in roughly 1.1 to 2.5 per cent of adults.Reference Palmer, Messina, Biletch, Grosel and Mahmoud1 The presence of CRSwNP severely degrades a patient’s quality of life by impairing natural nasal breathing, olfaction and overall daily functioning.Reference Orlandi, Kingdom, Smith, Bleier, DeConde and Luong2–Reference Mullol, Azar, Buchheit, Hopkins and Bernstein4 Furthermore, the disease is frequently linked to mental health challenges such as depression and anxiety, as well as sleep disturbances.Reference Mullol, Azar, Buchheit, Hopkins and Bernstein4 In Western nations, CRSwNP is predominantly driven by a type 2 (T2) inflammatory profileReference Kato, Schleimer and Bleier5; nevertheless, an individual patient may simultaneously exhibit multiple inflammatory pathways, including types 1, 2 and 3.Reference Kato, Schleimer and Bleier5, Reference Stevens, Schleimer and Kern6
Historically, physicians have managed CRS through a progressive treatment model, starting with topical intranasal corticosteroids (INCS) alongside saline irrigations, escalating to short regimens of oral steroids and ultimately utilising endoscopic sinus surgery (ESS) for stubborn cases. Nevertheless, a considerable proportion of individuals suffer from treatment-resistant disease despite receiving optimal medical and surgical care. This recalcitrant form is marked by rapid polyp regrowth, persistent loss of smell and the worsening of concurrent diseases like non-steroidal anti-inflammatory drug (NSAID) -exacerbated respiratory disease (N-ERD) or asthma.
Recently, a fundamental shift has transformed our comprehension of CRS pathogenesis, steering focus away from observable clinical traits toward underlying molecular endotypes. Identifying that T2 inflammation—driven by immunoglobulin E (IgE) and interleukins like IL-4, IL-5 and IL-13—is responsible for up to 80 per cent of severe CRSwNP cases has opened the door for highly specific pharmacological treatments. Biologic agents consist of monoclonal antibodies engineered via recombinant DNA techniques to neutralise these specific proteins.Reference Malik and Ghatol7 Currently, the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have authorised three such agents for CRSwNP: omalizumab (anti-IgE), dupilumab (anti-IL-4Rα) and mepolizumab (anti-IL-5).Reference Shin, Wilson, McKenna, Rosenfeld, Ammon and Crosby8
Previous systematic reviews and meta-analyses, such as those by Alshatti and Webb comparing functional ESS (FESS) to dupilumab,Reference Alshatti and Webb9 cost-utility analyses by Scangas et al.,Reference Scangas, Wu, Ting, Metson, Walgama and Shrime10 robust network meta-analyses by Oykhman et al.,Reference Oykhman, Paramo, Bousquet, Kennedy, Brignardello-Petersen and Chu11 and comprehensive assessments by the Cochrane collaboration,Reference Chong, Piromchai, Sharp, Snidvongs, Webster and Philpott12 have provided strong evidence regarding the general safety and efficacy of these biologic agents. However, translating these broad efficacy profiles into daily clinical practice remains challenging. Biologics carry substantial financial burdens and often demand continuous, potentially indefinite usage. As such, they are not designed to substitute standard interventions like ESS, but rather to act as a targeted medical strategy for a specific subset of patients.
Therefore, the primary hurdle for contemporary allergists, immunologists and rhinologists is navigating drug selection and identifying the ideal candidates. Building upon earlier systematic reviews, this narrative review aims to synthesise current guidelines and clinical data to address the following structural questions: (1) What are the precise clinical and endotypic parameters for selecting optimal candidates for CRSwNP biologic therapy? (2) What is the clinical evidence regarding the efficacy of FDA-approved biologics, and how should clinicians choose between them? and (3) What are the evidence-based protocols for evaluating treatment response and duration?
Materials and methods
Search strategy and databases
To conduct this comprehensive narrative review, an extensive literature search was performed across major recognised scientific databases, including PubMed/Medline, Scopus, Embase and Web of Science. The literature search encompassed articles published from 2016 to 2026.
Search terms and algorithms
Boolean operators (AND, OR) were utilised to combine specific keywords and Medical Subject Headings (MeSH) terms. The primary search string included: (“Chronic rhinosinusitis” OR “CRS”) AND (“Chronic Rhinosinusitis with Nasal Polyps” OR “CRSwNP” OR “nasal polyps”) AND (“biologic agents” OR “biologics” OR “type 2 inflammation”) AND (“dupilumab” OR “mepolizumab” OR “omalizumab”).
Inclusion and exclusion criteria
Inclusion criteria consisted of: (1) Peer-reviewed original research articles, including phase III randomised controlled trials (RCTs); (2) real-world clinical studies and observational cohorts evaluating the efficacy of biologics; (3) authoritative international guidelines and consensus statements (e.g., European Position paper on Rhinosinusitis and Nasal Polyps [EPOS], European Forum for Research and Education in Allergy and Airway Diseases [EUFOREA]); and (4) articles published in the English language. Exclusion criteria included: (1) Non-peer-reviewed preprints; (2) case reports with insufficient clinical data; and (3) abstract-only publications.
Data synthesis
Priority was given to large-scale, multi-centre, double-blinded clinical trials and authoritative international guidelines (e.g., EPOS) to guarantee the reliability and clinical relevance of the discussed data. Data were structurally categorised to address the three primary research questions outlined in the introduction.
Results
Literature search yield
The primary literature search yielded over 400 potential articles across the specified databases. Following the removal of duplicates and the screening of abstracts for relevance, 33 key publications, comprising phase III RCTs, real-world observational studies and authoritative international consensus guidelines (e.g., EPOS, EUFOREA), were selected for inclusion in this narrative synthesis to construct patient selection and drug choice algorithms.
Clinical and endotypic parameters for patient selection
The prescription of biologics is specifically indicated for individuals experiencing severe, refractory T2 inflammation who have not achieved relief from maximum medical therapy (INCS), extensive systemic corticosteroid (SCS) utilisation and prior surgical interventions.
To establish clear clinical boundaries, the EUFOREA and the EPOS introduced criteria suggesting that ideal candidates should have a history of ESS combined with at least three of the following five factors (or four factors if surgically naive)Reference Fokkens, Lund, Hopkins, Hellings, Kern and Reitsma13, Reference Fokkens, Viskens, Backer, Conti, De Corso and Gevaert14:
Indicators of type 2 inflammation: Blood eosinophil count ≥ 150 cells/μl (updated from 250 in the 2023 guidelines), tissue eosinophils greater than or equal to 10 per high-power field or total IgE greater than or equal to 100 IU/ml.
Systemic corticosteroid (SCS) dependence: Requirement of greater than or equal to two SCS courses annually or reliance on long-term, low-dose SCS.
Substantial quality of life (QoL) reduction: A Sino-Nasal Outcome (SNOT-22) score of greater than or equal to 40.
Severe olfactory dysfunction: Clinically confirmed anosmia.
Coexisting asthma: Requiring regular management with inhaled corticosteroids (Table 1).
EPOS/EUFOREA patient selection criteria for biologic therapy in CRSwNP
Table 1 Long description
Clinical criteria are listed alongside required thresholds or descriptions. Evidence of type 2 inflammation is defined as blood eosinophils at least 150 cells per microliter, tissue eosinophils at least 10 per high power field, or total immunoglobulin E at least 100 international units per milliliter. Systemic corticosteroid use is defined as at least two courses per year or dependence on long term low dose systemic corticosteroids. Quality of life impairment is defined as a Sino Nasal Outcome Test score of at least 40. Significant loss of smell is defined as clinically confirmed anosmia or severe hyposmia. Comorbidities are defined as asthma requiring regular management with inhaled corticosteroids. Surgical history is defined as documented evidence of previous endoscopic sinus surgery.
Note: Patients typically must meet three criteria if they have prior sinus surgery or four criteria if surgically naïve.
CRSwNP = chronic rhinosinusitis with nasal polyps; EPOS = European Position Paper on Rhinosinusitis and Nasal Polyps; EUFOREA = European Forum for Research and Education in Allergy and Airway Diseases; HPF = high-power field; IgE = immunoglobulin E.
“Uncontrolled” disease is classified as continuous or relapsing CRSwNP despite sustained INCS therapy, combined with at least one SCS treatment in the past two years or a history of sinonasal surgery. “Severe” disease is identified by bilateral polyposis (Nasal Polyp Score [NPS] of at least 4 out of 8) and lingering symptoms that necessitate supplemental therapy beyond INCS.Reference Fokkens, Viskens, Backer, Conti, De Corso and Gevaert14
Efficacy and navigating the choice between biologic agents
All three FDA-approved biologics—dupilumab, omalizumab and mepolizumab—have demonstrated significant efficacy in reducing polyp burden, recovering olfactory function and lowering dependency on systemic steroids compared to placebo in phase III trialsReference Gevaert, Omachi, Corren, Mullol, Han and Lee19–Reference Gevaert, Omachi, Corren, Mullol, Han and Lee22 (Table 2). However, selecting the most appropriate biologic requires moving beyond a “one-size-fits-all” approach and evaluating the patient’s specific comorbidities, treatable traits and biomarker profile.
FDA-approved biologic agents for CRSwNP
Table 2 Long description
Columns are, Biologic agent, Target mechanism, and Key indications and clinical notes. Dupilumab with footnote markers 8, 11, 20, 23, 24 targets IL 4 receptor alpha and blocks IL 4 and IL 13 signaling; indications listed are severe chronic rhinosinusitis with nasal polyps, atopic dermatitis, and severe asthma, with notes on first line use for polyp shrinkage, severe olfactory loss, or concomitant N ERD, and caution in patients with high baseline eosinophilia. Omalizumab with footnote markers 8, 10, 25 targets IgE and binds circulating IgE; indications listed are chronic rhinosinusitis with nasal polyps, moderate to severe asthma, and chronic idiopathic urticaria, with notes on use in patients with specific allergen sensitisation and elevated total IgE within dosing nomograms. Mepolizumab with footnote markers 8, 12, 26 targets IL 5 and inhibits eosinophil maturation and survival; indications listed are chronic rhinosinusitis with nasal polyps, severe eosinophilic asthma, and EGPA, with notes on preference for patients with moderate to severe baseline blood eosinophilia or comorbid EGPA.
CRSwNP = chronic rhinosinusitis with nasal polyps; FDA = United States Food and Drug Administration; IgE, immunoglobulin E; IL = interleukin; N-ERD = non-steroidal anti-inflammatory drug exacerbated respiratory disease.
Dupilumab: Originally authorised for severe atopic dermatitis, dupilumab targets the IL-4 alpha receptor subunit, inhibiting both IL-4 and IL-13 signalling.Reference Fokkens, Lund, Hopkins, Hellings, Kern and Reitsma13 Indirect treatment comparisons and network meta-analyses frequently suggest that dupilumab provides the most robust improvements in both subjective metrics (SNOT-22, smell scores) and objective metrics (Lund–Mackay CT scores, NPS) across the broader CRSwNP population. It is often considered the first-line biologic choice for patients whose CRSwNP is complicated by severe N-ERD or concurrent atopic dermatitis. However, dupilumab can provoke transient increases in peripheral eosinophils; thus, it must be used with caution in patients with baseline hypereosinophilia, as it carries the risk of unmasking or exacerbating underlying eosinophilic granulomatosis with polyangiitis (EGPA).Reference Wechsler, Akuthota, Jayne, Khoury, Klion and Langford26
Mepolizumab: Mepolizumab functions as an antagonist against IL-5, a cytokine critical for eosinophil maturation and survival.Reference Han, Bachert, Fokkens, Desrosiers, Wagenmann and Lee21 This agent is highly effective for patients whose disease is driven primarily by eosinophilia. Mepolizumab is explicitly FDA-approved for EGPA and severe eosinophilic asthma. Consequently, in patients presenting with CRSwNP alongside moderate-to-severe baseline blood eosinophilia (e.g., >500 cells/μl) or comorbid EGPA, mepolizumab is generally the preferred biologic over dupilumab.Reference Wechsler, Akuthota, Jayne, Khoury, Klion and Langford26–Reference Bachert, Desrosiers, Hellings and Laidlaw29
Omalizumab: Omalizumab mitigates T2 inflammation by binding to circulating IgE. Its efficacy was validated in the POLYP 1 and POLYP 2 trials, demonstrating significant improvements in patients with severe bilateral CRSwNP and baseline serum IgE levels ranging from 30 to 1500 IU/ml.Reference Gevaert, Omachi, Corren, Mullol, Han and Lee19, Reference Gevaert, Omachi, Corren, Mullol, Han and Lee25 Omalizumab is the biologic of choice for patients with a clear, dominant allergic phenotype—specifically those with perennial allergen sensitivities, chronic idiopathic urticaria or moderate-to-severe allergic asthma, provided their pre-treatment total IgE levels and body weight fall within the established dosing nomograms.Reference Lombardo, Piazzetta, Lobello, Lorenz, Gunder and Nahrath16, Reference Gevaert, Omachi, Corren, Mullol, Han and Lee22
Protocols for evaluating treatment response and duration
To minimise the financial burden and avoid prolonged ineffective treatment, international guidelines advise rigorous reassessment of therapeutic efficacy at the six-month and 12-month marks.Reference Shin, Wilson, McKenna, Rosenfeld, Ammon and Crosby8, Reference Fokkens, Lund, Bachert, Mullol, Bjermer and Bousquet15, Reference Platt and Brook17
At the six-month milestone, biologic therapy should be continued only if the patient reports subjective satisfaction combined with at least one measurable objective improvement. Acceptable thresholds include a greater than or equal to 1 point drop in NPS, a greater than or equal to 0.5 reduction in the congestion score, a SNOT-22 decrease of greater than or equal to 8.9, a greater than 0.5 increase in smell score (shifting from anosmia to hyposmia/normosmia) or a greater than or equal to 2 cm reduction on the total symptom visual analogue scale (VAS).Reference Shin, Wilson, McKenna, Rosenfeld, Ammon and Crosby8 If the patient experiences no meaningful alleviation of sinonasal symptoms, the medication should be halted, unless it is actively controlling a severe concurrent condition such as asthma.
After one full year of biologic therapy, the treatment may be maintained indefinitely if an optimal response is achieved—defined by a SNOT-22 score less than 30, total symptom VAS less than 5, congestion score less than 2 and a polyp score less than 4—without the need for oral steroids or revision surgery.Reference Shin, Wilson, McKenna, Rosenfeld, Ammon and Crosby8, Reference Bachert, Desrosiers, Hellings and Laidlaw29
Discussion
The introduction of monoclonal antibodies targeting T2 inflammation represents a paradigm shift in rhinology, transforming CRSwNP from a purely surgical disease to a medically manageable systemic condition. While earlier literature and systematic reviews frequently pitted biologics directly against revision ESS,Reference Alshatti and Webb9 current clinical frameworks recommend viewing these interventions as synergistic rather than mutually exclusive. As Han et al.Reference Han, Bosso, Cho, Franzese, Lam and Lane18 outlined in their stepped treatment algorithm, traditional INCS, high-volume steroid irrigations and ESS remain the foundation of care. Biologic therapies are best reserved specifically for post-surgical recurrences or for individuals who are medically unsuitable or unwilling to undergo surgery.
The critical takeaway for modern practitioners is the absolute necessity of precision medicine. The criteria for prescribing biologics for CRSwNP in early approvals were somewhat broad—often simply requiring an inadequate response to topical steroids. However, as this review highlights, the sustainable use of these costly medications demands strict adherence to the EPOS/EUFOREA selection criteria. This prevents the overwhelming of healthcare budgets and spares non-T2 patients from fruitless, high-cost regimens. Cost-effectiveness remains a highly debated issue; multiple cost-utility analyses, such as those conducted by Scangas et al.,Reference Scangas, Wu, Ting, Metson, Walgama and Shrime10 have demonstrated that while biologics significantly improve quality-adjusted life-years (QALYs), their cumulative annual costs currently far exceed those of revision ESS. Therefore, meticulous patient selection is not merely a clinical imperative but an economic one. Reserving biologics for patients with severe comorbid asthma or N-ERD, where the drug simultaneously treats both upper and lower airway disease, drastically improves the overall cost-effectiveness profile of the intervention.
Furthermore, this review emphasises that drug selection must be individualised based on the safety profile and endotypic markers of each patient, as supported by recent comparative meta-analyses.Reference Oykhman, Paramo, Bousquet, Kennedy, Brignardello-Petersen and Chu11 Rather than viewing the available biologics as interchangeable, clinicians should map the drug’s mechanism to the patient’s “treatable traits”. A patient with profound eosinophilia and asthma represents a different endotypic profile than a patient with perennial allergies and high IgE, or a patient with concurrent severe atopic dermatitis. By leveraging accessible biomarkers (blood eosinophils, total IgE) and comorbidity profiles, clinicians can select the most appropriate immunomodulator. Additionally, safety profiles must guide decision-making. While generally well-tolerated, dupilumab is associated with transient hypereosinophilia and a unique risk of conjunctivitis; omalizumab carries a rare but well-documented risk of anaphylaxis requiring post-injection observation; and mepolizumab can present with injection-site reactions.Reference Shin, Wilson, McKenna, Rosenfeld, Ammon and Crosby8, Reference Oykhman, Paramo, Bousquet, Kennedy, Brignardello-Petersen and Chu11, Reference Domínguez-Sosa, Cabrera-Ramírez, Marrero-Ramos, Dávila-Quintana, Cabrera-López and Carrillo-Díaz27 Clinicians must weigh these risks against the patient’s baseline health.
A notable limitation in current clinical practice is the reliance on systemic biomarkers. Blood eosinophils and serum IgE do not always perfectly correlate with local sinonasal tissue inflammation. While tissue eosinophil count via biopsy is highly accurate, it is an invasive measure. Future research must focus on validating non-invasive, local biomarkers, such as measuring cytokine levels in nasal secretions or exhaled breath condensates, to predict biologic responsiveness more accurately.
Despite these advancements, significant clinical hurdles remain. Standardised protocols for safely tapering biologic therapies in patients showing sustained remission have yet to be established. It remains uncertain whether lifelong administration is universally required or how quickly polyps might rebound upon therapy cessation. Additionally, as new biologics like tezepelumab (anti-TSLP) and benralizumab (anti-IL-5Rα) enter the market, head-to-head clinical trials will be essential to definitively rank the efficacy of these agents. Ultimately, matching the right medication to the right patient requires a cohesive, multidisciplinary alliance. The establishment of combined “airway clinics”—where rhinologists, pulmonologists and allergists collaboratively evaluate the patient—ensures that these transformative, yet expensive, biologic agents are reserved strictly for those whose underlying disease genuinely dictates such an advanced intervention.
• Biologic treatments provide a targeted therapy for severe, refractory chronic rhinosinusitis with nasal polyps (CRSwNP) driven by type 2 inflammation, acting as a complement to surgery rather than a complete replacement
• Three Food and Drug Administration (FDA) -approved agents (dupilumab, mepolizumab, omalizumab) significantly reduce polyp burden and symptoms by blocking specific molecular pathways like interleukin (IL) -4/13, IL-5 and immunoglboulin E (IgE)
• According to European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases (EPOS/EUFOREA) guidelines, ideal candidates have a history of sinus surgery alongside markers like high T2 biomarkers, steroid dependence, anosmia or comorbid asthma
• Drug choice should be individualised: dupilumab for broad efficacy/non-steroidal anti-inflammatory drug exacerbated respiratory disease (N-ERD), mepolizumab for high eosinophilia/eosinophilic granulomatosis with polyangiitis (EGPA) and omalizumab for concurrent severe allergic asthma
• Continued biologic therapy requires strict clinical reassessment at six- and 12-month intervals using objective scoring systems to confirm a meaningful symptomatic response
Conclusion
Selecting the most appropriate candidate for biologic intervention in CRS is fundamentally rooted in precision medicine, demanding a rigorous evaluation of both clinical disease burden and underlying molecular endotype. The ideal target population specifically encompasses individuals battling aggressive, recurring T2-mediated inflammation despite comprehensive medical and surgical management. Clinical red flags such as a history of repeated ESS, profound persistent anosmia and severe comorbid asthma or N-ERD strongly justify the use of monoclonal antibodies. By accurately phenotyping the patient—and selecting between dupilumab, mepolizumab and omalizumab based on specific comorbidities and biomarkers—healthcare providers can abandon generalised trial-and-error strategies. This collaborative, multidisciplinary framework ensures that the transformative potential of biologic agents is reserved strictly for those whose underlying disease biology genuinely dictates such an advanced intervention.
Funding sources
None. There are no financial disclosures of the authors.
Ethical approval
There was no need for ethical approval, because this is a review paper.
Informed consent
There was no need for informed consent, because this is a review paper.
Competing interests
Nuray Bayar Muluk declares that she has no conflict of interest.
Author contributions
Nuray Bayar Muluk: Planning, designing, literature survey, evaluation of literature search, writing, submission.
Availability of data and materials
All data for this review are presented in this paper.
Consent for publication
The author gives consent for publication.
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