Treating & Managing CRSwNP

CRSwNP is a chronic condition that can be managed with proper treatment to reduce symptoms and improve quality of life.¹ Successful management of the disease may require multiple therapeutic interventions and long-term treatment to prevent recurrence.¹ Treatment options include nasal saline irrigation, intranasal corticosteroids (INCS), functional endoscopic sinus surgery (FESS), corticosteroid-eluting sinus implants, and biologics.¹

Nasal saline irrigation

Nasal saline irrigation is part of first-line therapy for patients with CRSwNP that improves mucociliary function by flushing out mucus, inflammatory debris, and allergens.¹ The treatment poses few risks if performed properly.² Patients should be advised how to clean irrigation devices and to use distilled, sterilized, or boiled water to avoid infection.^1,2

Intranasal corticosteroids

Intranasal corticosteroids (INCS) are a first-line treatment for CRSwNP and a cornerstone of maintenance medical treatment.^1,3 INCS can lead to significant improvement in symptoms in most patients, reducing polyp size and increasing nasal airflow.⁴

There are a variety of delivery systems for INCS including sprays and an exhalation-driven delivery system (EDS).¹ Proper technique when administering INCS is necessary to achieve the maximal therapeutic effect.¹

INCS sprays are generally well tolerated, with irritation of the nasal mucosal sometimes leading to epistaxis.¹ On rare occasions nasal septum perforation can occur.¹ The risk of these adverse events can be reduced by using the lowest effect medication dose and ensuring proper delivery technique.¹ Note that standard INCS sprays do not always reach target areas of the nasal cavity where polyps form.¹ If initial treatment with INCS spray does not provide adequate relief, consider adjusting treatment to a different delivery method, such as EDS.¹

The EDS device consists of a sealing nosepiece and flexible mouthpiece that administers medication as the patient exhales.⁴ EDS may be more convenient for patients who travel frequently and may be preferred by patients with eustachian tube dysfunction who have increased symptoms with irrigation.¹

Side effects of INCS via EDS include epistaxis, nasal septal ulceration, and reddening of the nasal mucosa¹. Patients using EDS should receive annual eye exams to monitor for glaucoma and cataracts, since medication delivery close to the orbit may increase the risk of these conditions.¹ Consult a patient’s ophthalmologist before using EDS in patients with a history of these diseases.¹

Oral corticosteroids

Patients with severe nasal blockage, severe nasal congestion, or anosmia may benefit from a short course of oral corticosteroids (OCS).¹ Although these medications can effectively reduce the size of nasal polyps, they are not recommended for prolonged use due to the significant burden of adverse effects.¹ Rare but serious side effects can occur with short term OCS use including hyperglycemia in people with diabetes or prediabetes, mood changes, and arrythmias.¹

Surgical management

Functional endoscopic sinus surgery (FESS), also called endoscopic sinus surgery (ESS), is considered standard of care for patients whose symptoms are not adequately controlled with medication.³ The surgery involves removal of the nasal polyps and surrounding inflammatory tissue, facilitating sinus drainage and allowing for improved medication delivery after surgery.^1,3 The scope of surgery is controversial.⁶

Indications for FESS include:

Severe symptoms
Nasal polyps prevent use of topical medication
Bony erosion
Disease extends beyond the sinus cavities¹

Note that medical management is still necessary after surgery because FESS does not treat the underlying inflammatory condition.^1,3 Even with medical management, nasal polyps and associated symptoms may recur.¹ A recurrence rate of 15%-20% within 5 years has been reported in CRSwNP patients who underwent FESS.⁶ In patients with recurring symptoms after surgery, treatment options include INCS, corticosteroid-eluting sinus implants, biologics, and revision surgery.¹

Corticosteroid-eluting sinus implants

Corticosteroid-eluting sinus implants are an in-office treatment option for patients who have recurrent nasal polyps after surgery.³ The sinus implants allow for localized medication delivery and are generally well tolerated³. In a prospective cohort of CRSwNP patients who received corticosteroid-eluting sinus implants, two cases of acute sinusitis were reported³. There is a lack of expert consensus on the use of this treatment.³

Biologics

Biologics for CRSwNP are monoclonal antibodies that target specific inflammatory pathways and can be considered in patients who have type 2 inflammation⁷ . Biologics may be considered as an alternative to surgery for patients who have contraindications for surgery, a strong preference against surgery, or comorbidities such as asthma that could also be treated with a biologic.¹

Three biologics have been FDA-approved for CRSwNP: dupilumab (anti-IL-4/13), omalizumab (anti-IgE), and mepolizumab (anti-IL-5).^1,6 In addition, benralizumab (anti-IL-5), reslizumab (anti-IL-5), and tezepelumab (anti-TSLP) are currently being studied as additional biologic options for CRSwNP.^1,6 These are currently FDA-approved for severe asthma, but more studies are needed to determine their effectiveness in CRSwNP.^1,6-15 The risks and benefits for each biologic therapy vary due to their differing mechanisms of action.³

Dupilumab is an IgG4 monoclonal antibody targeting the IL-4 receptor that inhibits signaling of IL-4 and IL-13, two key cytokines in type 2 inflammation.¹³ The LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52 studies showed that dupilumab reduced nasal polyp size (-34% and -37%), decreased sinus opacification, and reduced symptoms including nasal congestion (relative change -59% and -54%) and anosmia.^,8,13 Common adverse events included nasopharyngitis, worsening asthma, headache, epistaxis, and redness of the injection site.⁴
Mepolizumab is a monoclonal antibody targeting IL-5, a mediator of tissue eosinophilia in CRSwNP^5,8. The SYNAPSE study showed that mepolizumab reduced nasal polyp size (relative change -17%), improved nasal symptoms including congestion (-47%) and loss of smell, and reduced the need for nasal surgeries and OCS treatment in patients with CRSwNP.^8,14 Most common adverse events included nasopharyngitis, headache, and epistaxis.¹⁴

Omalizumab is a humanized recombinant DNA-derived IgG1 monoclonal antibody that binds to the Fc region of circulating IgE, preventing IgE from binding to the high affinity IgE receptor and inhibiting one pathway involved in type 2 inflammation.¹⁵ IgE activates type 2 inflammatory cells and is thought to play a role in the development of nasal polyps and CRSwNP pathogenesis.⁶ The POLYP1 and POLYP2 studies showed that omalizumab improved clinical and patient-reported outcomes in patients with CRSwNP including reduced polyp size (-17% and -14%) and reduced nasal congestion (-37% and -30%).^8,15 It was overall well tolerated. Common adverse events included headache, nasopharyngitis, and injection site reactions and pain.¹⁵

Currently there are no guidelines for which biologic should be used first and direct comparisons are needed.⁵ Considerations for starting biologic therapy include:

Type 2 inflammatory polyps
SNOT-22 score >40 despite adherence to corticosteroid treatment and previous surgery
Use of corticosteroids in the past 12 months
Additional comorbidities that can be treated with biologics.³

The success of a biologic treatment should include both clinician- and patient-reported outcomes¹⁰. Proposed reasons to continue biologic therapy once started include improved quality of life or >50% reduction in systemic corticosteroid use without additional surgery.³

References

Buccheit K, Holbrook E. Chronic rhinosinusitis with nasal polyposis: Management and prognosis. UpToDate. https://www.uptodate.com/contents/chronic-rhinosinusitis-with-nasal-polyposis-management-and-prognosis
deShazo R, Kemp S. Pharmacotherapy of allergic rhinitis. UpToDate. https://www.uptodate.com/contents/pharmacotherapy-of-allergic-rhinitis
Ramkumar SP, Lal D, Miglani A. Considerations for shared decision-making in treatment of chronic rhinosinusitis with nasal polyps. Front Allergy. 2023;4:1137907.
Han JK, Bosso JV, Cho SH, et al. Multidisciplinary consensus on a stepwise treatment algorithm for management of chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 2021;11:1407-1416.
Optinose exhalation delivery system (EDS). https://xhancehcp.com/exhalation-delivery-system
Kim SD, Cho KS. Treatment strategy of uncontrolled chronic rhinosinusitis with nasal polyps: A review of recent rvidence. Int J Mol Sci. 2023;24:5015.
Fokkens WJ, Viskens AS, Backer V, et al. EPOS/EUFOREA update on indication and evaluation of Biologics in Chronic Rhinosinusitis with Nasal Polyps 2023. Rhinology. 2023;61(3):194-202.
Gomes PL, Miglani A, Marino MJ, Lal D. Biologics for chronic rhinosinusitis with nasal polyps. https://bulletin.entnet.org/clinical-patient-care/article/22881642/biologics-for-chronic-rhinosinusitis-with-nasal-polyps
Benralizumab (Fasenra®) injection. Prescribing information. AstraZeneca AB; 2021.
Reslizumab (Cinquair®) injection. Prescribing information. Teva Respiratory, LLC; 2020.
Tezepelumab-ekko (Tezspire®) injection. Prescribing information. Amgen Inc. and AstraZeneca AB; 2023.
Rank MA, Chu DK, Bognanni A, et al. The Joint Task Force on Practice Parameters GRADE guidelines for the medical management of chronic rhinosinusitis with nasal polyposis. J Allergy Clin Immunol. 2023;151:386‑398.
Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019;394:1638-1650.
Han JK, Bachert C, Fokkens W, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2021;9:1141-1153.
Gevaert P, Calus L, Van Zele T, et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013;131:110-116.e1.