Key points are not available for this paper at this time.
Chronic rhinosinusitis (CRS) represents a significant health care problem in the United States and CRS patients have a significant decreased quality of life. CRS is typically divided into two phenotypes based on the presence or absence of nasal polyps which are commonly associated with CRS: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). The prevalence of CRS in the United States is estimated to range from 2.1% to 13.8% and specifically, the prevalence of CRSwNP ranges from 1.7% to 2.7% of the US population.1 The initial recommended medical therapy for CRSwNP includes saline irrigations, topical intranasal corticosteroids (INCSs) via several methods including sprays, irrigation, atomization, and short courses of systemic corticosteroids.2 An intranasal mometasone nasal spray became the first US Food and Drug Administration (FDA) approved treatment for CRSwNP in 2004. Other medical treatment options have since been developed over the past several years to address uncontrolled inflammation and persistent symptoms of CRSwNP. Recently, new therapeutic options have been approved by the FDA for the treatment of CRSwNP, including a topical intranasal fluticasone delivered via an exhalation delivery system (EDS-FLU), a mometasone eluting sinus implant, and monoclonal antibody treatments. Endoscopic sinus surgery (ESS) is also an option for patients who do not adequately respond to appropriate medical therapy. Aspirin desensitization may be used post-ESS as a preventive measure in the aspirin-exacerbated respiratory disease (AERD) endotype of CRSwNP. There are an estimated 600,000 ESSs performed annually in the US with a reported surgical recurrence rate of 16.2% within 90 months among patients with CRSwNP.3 The availability of new treatments and the presence of multiple therapeutic options including several medical and procedural interventions for a specific disease can cause confusion among providers regarding the optimal sequence to use those treatment modalities. This has resulted in the development of stepwise treatment paradigms based on evidence and expert opinion which can serve as a basis for reducing unwanted variation and improve quality of care.4, 5 Such living documents are regularly updated with the continual advent of new therapeutic modalities for patients and their providers. With the proliferation of new FDA-approved treatments for CRSwNP available to clinicians for CRSwNP patients, experts with diverse backgrounds and members of national societies vested in the advancement of the care of patients with CRSwNP (ARS, AAAAI, AAOHNS, ACAAI, AAOA) proposed a stepwise treatment paradigm that incorporates both medical and surgical strategies, based on the currently available scientific evidence for FDA-approved treatments for CRSwNP. It should be noted, however, that the views and opinions of the authors in the development of this algorithm are those of the authors alone and are not necessarily held by the organizations of which the authors are members. Treatment decisions ideally should also incorporate the use of a shared-decision making approach with CRSwNP patients.6 The scientific committee of 11 experts including both otolaryngologists and allergists was established to review published research on the management of CRSwNP and develop a stepwise treatment paradigm of FDA-approved treatment options. The committee members are recognized experts in research and clinical practice who contributed in a voluntary capacity. The panel of experts have been active participants in national societies dedicated to the advancement of the care of patients with CRSwNP, including the American Rhinologic Society (ARS), American Academy of Allergy Asthma and Immunology (AAAAI), American Academy of Otolaryngology p = 0.018) and ethmoid obstruction on a 100-mm visual analog scale (VAS) (−16.5 ± 27.80 vs. 4.96 ± 21.96; p < 0.001) compared to controls. The RESOLVE II trial studied 300 enrolled patients randomized in a 2:1 fashion into treatment and control groups over a similar time period, similar to RESOLVE I, followed by serial endoscopies graded by a centralized independent reviewers. Compared with the control group, the treatment group achieved significant reductions in both NCS (−0.80 ± 0.73 vs. −0.56 ± 0.62; p = 0.0074) and bilateral NPS (−0.56 ± 1.06 vs. −0.15 ± 0.91; p = 0.0073). At day 90, implants were also associated with significant reductions in four of five secondary endpoints compared with controls. In both studies, the overall incidence of adverse events was similar between treatment and control groups. Dupilumab is an immunoglobulin G4 (IgG4) antibody that binds to the interleukin 4 (IL-4) receptor α (IL-4Rα), a shared subunit important in both IL-4 and IL-13 signaling. Binding of dupilumab to this receptor blocks circulating IL-4 and IL-13 from binding to IL-4Rα, thereby inhibiting one of the key pathways in the type 2 inflammatory cascade. Two phase III randomized double-blind, placebo-controlled studies, SINUS-24 (n = 276) and SINUS-52 (n = 448) evaluated the efficacy and safety of dupilumab as an add-on therapy in adult patients with persistent CRSwNP.9 By week 24, dupilumab statistically improved both co-primary endpoints of NPS (−2.06, p < 0.0001) and NCS (−0.89, p < 0.0001). These pivotal studies demonstrated that dupilumab was effective in reducing nasal polyp size, decreasing sinus opacification on computed tomography (CT) scans, and reducing key CRS symptoms such as nasal congestion and anosmia compared with placebo. The most common adverse effects were nasopharyngitis, worsening asthma, headache, epistaxis, and injection-site erythema. Omalizumab is an IgG1 monoclonal antibody that binds to the Fc region of circulating IgE antibody. It prevents IgE from binding to the FcεR1, thereby suppressing one of the pathways of the type 2 cascade. There were two phase III studies (POLYP 1 and POLYP 2) that evaluated omalizumab for CRSwNP, followed by an open label study.10 In these pivotal randomized, double-blind, placebo-controlled studies, patients were either treated with omalizumab or placebo with background intranasal mometasone spray for 24 weeks. A total of 265 CRSwNP patients were enrolled. Significant change in NPS was observed between treatment and placebo groups for POLYP 1 (−1.08 vs. 0.06, p < 0.0001) and POLYP2 (−0.90 vs. −0.31, p = .0140). The change in NCS was −0.89 versus 0.35 (p = 0.0004) in POLYP 1 and −0.70 versus −0.20 (p = .0017) in POLYP 2. The SNOT-22 score also improved −24.7 versus −8.6 (p < in POLYP 1 and versus (p < in POLYP 2. the open label study, the CRSwNP subjects who received omalizumab to improve in NCS, and SNOT-22 through week when omalizumab was at week there was worsening of the key during the the open label study, the CRSwNP subjects who received omalizumab to improve in NCS, and SNOT-22 through week In the open label study for the initial placebo group and improvements of when omalizumab was at week there was worsening of the key during the It is important to the time in which clinical to a treatment are This can patients who are not to treatment and in of an therapy and medical There are several monoclonal currently for the treatment of at dupilumab and omalizumab are currently FDA In the phase III studies of CRSwNP patients, omalizumab significantly polyp size and nasal congestion compared with placebo by 24 in study of CRSwNP patients, omalizumab improved nasal symptoms such as rhinorrhea, and sense of as as 4 into in phase III studies of CRSwNP, dupilumab improved both nasal polyp size and nasal congestion within the first 4 to of to improvements in symptoms the treatment period in the SINUS-24 study and in of by the of and of patient-reported symptoms SNOT-22 and total symptoms 2 to 4 treatment patients in the dupilumab and omalizumab studies were on a background treatment of topical nasal steroid A phase III study, the efficacy of which was In a randomized placebo-controlled trial was performed in patients with and refractory nasal polyposis sinus surgery. treated with had significantly improved nasal obstruction and NPS by week when compared with placebo. The group had of nasal surgery and for systemic corticosteroids during the the among the patients on average have reported improvements in nasal symptoms as as 4 to weeks. the clinical studies for the two currently FDA-approved for CRSwNP primary endpoints at 6 This that patients should treatment with a for 6 months before clinical improvement is After this if no is the should consider the therapy and using an for type 2 inflammation the of key in and in CRSwNP patients. therapy before or surgery has not been studied and there is no evidence to this that can this for a the of of CRSwNP, the of recurrence of nasal polyps or the specific endotype for CRSwNP the of of prior the presence of to and the of these the of the CRSwNP with nasal polyps and sinus and a of without any significant This has SNOT-22 and would that initial there would be treatment with an oral corticosteroid followed by topical With the advent of a approved enhanced topical delivery system for nasal polyps, of these If there is treatment with additional like intranasal and for should be Surgery is in these is a therapy. the other is the refractory CRSwNP This is who has presence of to polyps, SNOT-22 and and to otolaryngologists and allergists would that this would a of interventions including a oral and topical therapies such as type 2 and for desensitization in as patients. in the treatment options most in CRSwNP with of the between otolaryngologists and allergists with this group of among them the most for of and shared making between the and the shared making is for all is when there can be one to the is in this a should be considered. Such an would not the to the also the to the There are not studies the these are The of is based on the at the have to of their and to if these treatments for the The of these therapies compared with those of time and studied therapies such as ESS and desensitization to be considered on an the to the be used before or sinus surgery for the management of nasal is including of and as well as should all be of the for all of these patients, treatment options are to available for to to reduction in inflammatory and to and side effects of systemic topical intranasal corticosteroids have an important in therapy for CRSwNP. The currently available FDA-approved modalities from spray to exhalation delivery to and delivery of corticosteroids in nasal saline irrigations, or is also in clinical In a placebo-controlled corticosteroid were shown to have superior clinical compared with a standard nasal corticosteroid spray when used in CRSwNP patients In this study, patients who underwent ESS received either 2 of mometasone daily via nasal spray or for Each was both a nasal and spray were blinded as to which the After months of the steroid group was to have significantly greater improvement in nasal and compared with the spray on the evidence in the corticosteroid have been recommended in the treatment of CRSwNP by the on this current algorithm on FDA-approved treatments for CRSwNP, steroid were the of evidence for this non–FDA-approved therapy. of topical corticosteroids and effective delivery into the of the nasal cavity and is with sprays, which in the nasal region and The EDS deposition in the posterior nasal and superior with either the of the can which can be further by the presence of of polyps and of the to for topical using a delivery once polyps sinus difficult to the polyp can also topical delivery into the sinus with topical nasal steroid and may further of these treatments. surgery for of corticosteroid-eluting sinus which of by in for The of such is that the is to in with the implant, the of the total sinus because the is from the implant over and there is a for multiple to and implants to control over persistent The to the medical for nasal polyps is the option for therapy. efficacy are for these and The with these of to their use at this further and regarding the of type 2 inflammation in CRSwNP and associated is the for treatment by and limitations the of to other as well as in and with may be a for patients. effects in to be and are not to other medical the of treatment is the is This potential regarding and health that use of as a primary therapeutic for CRSwNP with CRSwNP a significant to the A study estimated an of compared with without The is in those with overall of in the of surgery. These do not for from estimated at and do not the of these increased has been to the of treatment strategies, including surgical and medical options. is important to consider as specific to patients, and may be the of treatment is also an important as ESS has may be in may have initial There have been a of for CRS ESS to medical therapy. study with that ESS was the most for any to and time greater A similar study in a separate estimated with that ESS was the for CRSwNP at an It is important to that these studies a revision surgery rate of and were before the availability of treatments such as A ESS to dupilumab over a time showed that ESS was the at any of revision surgery and at any of dupilumab these are they and are not to to the these the to consider ESS before in most In and January the for and in Allergy and organized two expert of and allergists from and the United The of the was to the available evidence and develop for the of in CRSwNP patients with or without as well as CRS control and disease The expert established five that were considered in the for of in CRSwNP (1) evidence of type 2 inflammation (2) for systemic corticosteroids in the past 2 significant of significant loss of smell, and of was reached that were indicated in patients with bilateral nasal polyposis and a of prior surgery if of the five were in patients with bilateral nasal polyposis without a of prior four of the five would to be for to be The in 2020 further the of as persistent or inflammation having received at least one course of systemic corticosteroids in the preceding 2 years prior was further by as patients with a NPS of and with persistent symptoms symptoms were also by several including a loss of score NCS SNOT-22 score of points and total symptom of 10 to of treatment were also and were as (1) and of of type 2 (2) nasal polyps, such as and such as The expert to to therapy. The five were (1) nasal polyp size, (2) for systemic improved quality of improved sense of smell, and of A was as if one to two were if to four were and if all five were was reached that treatment should be evaluated of and if no in any of the five were were in the 2020 to treatment and for of therapy. 6 and months of treatment was proposed with use of patient-reported including NCS, sense of score, as well as NPS If any one of the improved reduction by reduction of NCS by sense of from anosmia to or score by and NPS by the committee that of a would be After months of to a was also by demonstrated improvements in and making was with that are currently not available to if a respond to to a treatment and to patients was also as an important It should be that the initial consensus was developed based on the current available evidence at the prior to any FDA-approved for CRSwNP and of any phase III In the of implants and EDS-FLU were not considered when this consensus was the expert also recognized that there were multiple that These (1) of treatment in with of type 2 (2) research to to of effects of of of treatment and of between and sinus and After appropriate of CRSwNP including of of and INSs are considered therapy for CRSwNP In to a short of systemic corticosteroids be recommended if not should be evaluated treatment with 1 of with of evidence of persistent inflammation and associated If there is and evidence of an oral steroid can be considered or EDS-FLU may not be if there is nasal If sinonasal inflammation the initial of should be considered when appropriate. The initial of and to for type 2 such as and total If a with CRSwNP to improve systemic steroids, or ESS may be considered For patients with to or corticosteroid asthma, who have either a to ESS or a may be an option at this the should in that ESS may also improve medical management for CRSwNP should the use of topical corticosteroids such as an steroid irrigations, or steroid sinus Aspirin desensitization can be an option for patients with and should be with surgical steroid and desensitization are not FDA-approved treatments for nasal polyps, these treatments have shown to be in symptom and inflammation If the to have persistent sinonasal inflammation ESS and to medical there are other options available that the use of the steroid eluting sinus implants in patients who have had prior sinus desensitization for patients, and oral making this is in to and availability as well as of therapeutic options. A discussion including and of each option is important in to the for the to to
Han et al. (Mon,) studied this question.