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 a 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 option 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 effective 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 inflamed tissue, facilitating sinus drainage and allowing for improved medication delivery after surgery.^1,3 The scope of surgery is controversial.⁶ Indications for FESS include¹:

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

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 include³:

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

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 Evidence. Int J Mol Sci. 2023;24(5):5015. doi: 10.3390/ijms24055015.
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.