Chronic Rhinosinusitis with Nasal Polyposis
- Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease of the nasal mucosa and sinuses that lasts at least 12 weeks.
- CRSwNP affects about 2–4% of people with symptoms such as smell loss, nasal obstruction, thick nasal drainage, and facial pressure.
- Some patients with CRSwNP also have comorbid asthma and develop acute respiratory reactions to nonsteroidal anti-inflammatory drugs (NSAIDs).
Table 1. Topical Steroids
|Intranasal corticosteroid (INCS) delivery type||Description||Usual administrator|
|Stent||Steroids are found within the matrix of a device implanted in the nasal cavities and are gradually released over a timespan following the operation. The implant exerts a mechanical function in maintaining sinus patency. The implanted device is either absorbed by the mucosae or is surgically removed.||Administered by surgeons intra-operatively|
|Spray||Corticosteroids are suspended in an aqueous medium with varying concentrations. The delivery is entirely self-administered, with the patient having to press the applicator after clearing the nostrils and assuming a proper head position.||Self-administered|
|Rinse||Steroids are suspended in a saline solution. The compound is first inserted into a recipient (i.e., syringe, bottle) and then squeezed into a nostril, having the head tilted sideways. The process is repeated for both nostrils several times as instructed either by study investigators (if in a trial) or by the treating physician.||Self-administered|
|Exhalation delivery system (EDS)||Corticosteroids are suspended in an aqueous medium. The delivery system uses the patient's exhaled breath to propel medication into the inner nose. By exhaling through the EDS, the patient physiologically seals the soft-palate, isolating the nose from downstream airways, preventing drug dispersion.||Requires specific device and some basic training.|
|Drops||Corticosteroids within an aqueous suspension. A proper administration requires patients to adopt and maintain specific body postures as described either by study investigators (if in a trial) or in the patient information leaflet. The daily dose can either be split between nostrils or administered into a single nostril per day, alternating between the two.||Self-administered. |
Requires specific instructions.
- The network meta-analysis linked to this guideline showed that delivery method of INCS was potentially important. INCS stent, spray, and EDS are among the most beneficial of the INCS delivery methods across multiple patient-important outcomes.
- The costs, availability, accessibility, and practical implications of the different methods of INCS delivery are likely to influence patient decision making.
- There is moderate certainty of evidence for the safety of INCS spray but safety may vary among the other delivery options. There is low or very low certainty in the safety of INCS using delivery methods other than spray.
- INCS have small treatment effect sizes. Patients with severe or rapidly recurrent disease may value more treatments with larger reductions in symptoms.
- There is probably uncertainty in the value and importance patients put on the outcomes that patients consider critical to decision making.
- For patients who have a symptom for which the improvement was considered to be important while receiving treatments other than biologics (i.e., INCS, surgery, or aspirin therapy after desensitization [ATAD]), not using biologics may be preferred.
- For patients using INCS for at least 4 weeks and who continue to have high disease burden, or for patients who have higher disease severity at presentation, biologics may be preferred over other medical treatment choices.
- There is variability in efficacy among the biologics and this may influence the overall choice. See Table 2 for more information.
- Patients who value not having the burden of payment and insurance approvals may be less likely to choose biologics. Patients who want to avoid the inconvenience of trialing potentially less effective medical therapies may prefer biologics.
- In aspirin exacerbated respiratory disease (AERD) specifically, biologics may be preferred over ATAD for patients who have increased risk of harms associated with daily aspirin therapy, or in patients who value the most efficacious therapies and/or patients who wish to avoid a strict daily oral medication regimen and its associated initial desensitization procedure.
- Patients with comorbid diseases that lead to a dual indication for biologic treatment may be a reason to choose biologics in general and even specific biologics.
- Consider risks that impact the safety of performing an aspirin desensitization such as severe poorly controlled asthma. Consider risks that impact safety of long-term aspirin use such as conditions or treatments that increase bleeding risk.
- Biologics may be preferred over ATAD in AERD for patients who have increased risk of harms with ATAD or in patients who value the most efficacious therapies and/or avoiding a strict daily oral medication regimen and its associated desensitization procedure.
- Patients intolerant to NSAIDs and who require an NSAID for alternative indications may prefer ATAD over other options.
Table 2. Conditions Important for Shared Decision-Making
INCS - Delivery Method
|Improve quality of life (QoL)||✔||✔|
|Reduce need for surgery||✔||✔||✔|
Adverse effects: No diferent than placebo.
Additional issues: Spray is over the counter, and cost is not prohibitive to most.
|Reduce need for surgery||✔|
Adverse effects: Not diferent than placebo.
Additional issues: Very costly, needs long term treatment, no comparison with surgery and uncertain if it should be used with, before, or afer surgery. May be considered more favorably in those with other comorbidities that are treated with biologics.
Aspirin therapy after desensitization in patients with AERD
- Improves symptoms and quality of life
- Not different than placebo for smell
- May not decrease need for oral corticosteroids (OCS) or rescue surgery
- Bleeding risk and gastrointestinal (GI) side efects more common than placebo.
- Note: For every 10 people treated with ATAD, 1 will have an adverse sufficiently event enough to stop treatment.
- Affordable, long term treatment
Table 3. Biologic Agents for CRSwNP
|Type||Indication||Dose||WARNINGS AND PRECAUTIONS|
|Interleukin-5 receptor alpha-directed cytolytic monoclonal antibody (IgG1, kappa)||Add-on maintenance treatment of patients with severe asthma aged 12 years and older and with an eosinophilic phenotype||30 mg subcutaneously every 4 weeks for the first 3 doses, followed by once every 8 weeks thereafter|| |
|Interleukin-4 receptor alpha antagonist||Add-on maintenance treatment in adult patients with inadequately controlled CRSwNPa||300 mg given subcutaneously every other week|| |
|Mepolizumab NUCALA||Interleukin-5 (IL-5) antagonist monoclonal antibody (IgG1 kappa)||Add-on maintenance treatment of adult patients 18 years and older with CRSwNPb||100 mg administered subcutaneously once every 4 weeks|| |
|Anti- IgE antibody||Add-on maintenance in adult patients 18 years of age and older with CRSwNPc||75–600 mg subcutaneously every 2 or 4 weeks|| |
a Also indicated for atopic dermatitis, asthma, eosinophilic esophagitis and prurigo nodularis.
b Also indicated for eosinophilic asthma, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome.
c Also indicated for moderate to severe persistent asthma and chronic spontaneous urticaria (CSU).
- AERD: Aspirin (nonsteroidal Anti-inflammatory) -exacerbated Respiratory Disease
- ATAD: Aspirin Therapy After Desensitization
- CRSwNP: Chronic Rhinosinusitis With Nasal Polyps
- CSU: Chronic Spontaneous Urticaria
- EDS: Exhalation Delivery System
- GI: Gastrointestinal
- INCS: Intranasal Corticosteroid
- JTFPP: Joint Task Force On Practice Parameters
- NSAID: Nonsteroidal Anti-inflammatory Drug
- OCS: Oral Corticosteroids
- QoL: Quality Of Life
Bognanni A, Chu DK, Rank MA, Bernstein J, Ellis AK, Golden D, Greenhawt M, Hagan JB, Horner CC, Ledford DK, Lieberman J, Luong AU, Marks LA, Orlandi RR, Samant SA, Shaker M, Soler ZM, Stevens WW, Stukus DR, Wang J, Peters AT. Topical corticosteroids for chronic rhinosinusitis with nasal polyposis: GRADE systematic review and network meta-analysis. J Allergy Clin Immunol. 2022 Dec;150(6):1447-1459.
Oykhman P, Paramo FA, Bousquet J, Kennedy DW, Brignardello-Petersen R, Chu DK. Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: A systematic review and network meta-analysis. J Allergy Clin Immunol. 2022 Apr;149(4):1286-1295.
Chu DK, Lee DS, Lee KM, Schunemann HJ, Szczeklik W, Lee JM. Benefits and harms of aspirin desensitization for aspirin exacerbated respiratory disease: a systematic review and meta-analysis. Int Forum Allergy Rhin. 2019;9:1409-19.