Antibody-based therapeutics for chronic rhinosinusitis with nasal polyps.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory condition with heterogenous underlying endotypes, the most common being type 2 mediated inflammation. Several biologics have been developed to target specific pro-inflammatory cytokines and their receptors with proven efficacy in both quantitative and qualitative outcomes in patients with severe uncontrolled disease. However, there is an ongoing debate on the role of biologics relative to conventional therapies for CRSwNP and their efficacy in patient subgroups with non-polyp type 2 disease. AREAS COVERED: This review examines the evidence on the efficacy and safety of biologics in CRSwNP, recommendations for their use, and discusses the broader economic factors influencing their application in clinical practice. EXPERT OPINION: Emerging real-life data demonstrating the variable efficacy of the available biologics for patients with CRSwNP, coupled with the high cost compared to conventional therapies such as surgery, renders biologics to be considered as an add-on therapy in the majority of cases. However, ongoing research into increasing biologic dose intervals and novel therapies targeting alternative pathways may offer a more cost-effective and sustainable option in future.

[New manifestation of a type 2-inflammation in the upper respiratory tract with nasal polyposis under treatment with an asthma biologic]. / Neumanifestation einer Typ-2-Inflammation im Bereich der oberen Atemwege mit Polyposis nasi unter einem Asthmabiologikum.

INTRODUCTION: For 7 years we gained experience of how asthma and chronic rhinosinusitis with nasal polyposis respond to biologics. In contrast, it is much less known, how ASA/NSAID intolerance (Widal's disease) behaves under biologicals. We therefore describe the case of a patient with both clinical conditions who reacted with a severe intolerance reaction under perioperative metamizole administration.

[A comparative study of the effectiveness of azoximer bromide and surgery on the quality of the life of patients with chronic rhinosinusitis without nasal polyps]. / Sravnitel'naya otsenka vliyaniya azoksimera bromida i khirurgicheskogo lecheniya na kachestvo zhizni patsientov s khronicheskim rinosinusitom bez polipov.

OBJECTIVE: The aim of this study was to compare the effects of azoximer bromide and surgery on the quality of life of patients with chronic rhinosinusitis (CRS) without polyps. We also wanted to examine changes in the patient's emotional state and the nature of their complaints. MATERIAL AND METHODS: The results of using the Visual Analogue Scale (VAS) and the Sino-Nasal Outcome Test-22 (SNOT-22) questionnaire in patients with CRS without severe or moderate-severe polyps, before treatment and 3 months after treatment, are presented. Patients, depending on their choice, were treated with functional endoscopic intervention or a course of 6 mg/ml azoximer bromide (1 ml per day, a course of at least 10 days). RESULTS: The median [interquartile range] score for VAS in patients before azoximer bromide treatment was 6.7 [6.3; 7.05] points, after treatment 4.2 [3.50; 4.70] points. The median [interquartile range] of VAS scores in patients before surgical treatment was 6.4 [6.1; 6.9] points, and after 4.8 [4.50; 5.30] points. The median [interquartile range] of the SNOT-22 score before azoximer bromide treatment was 33 [32; 36] points, after treatment - 24 [22; 25] points. The median [interquartile range] of the SNOT-22 score before surgery was 34 [32; 36] points, after treatment - 19 [18; 21.25] points. CONCLUSION: Azoximer bromide treatment and surgery improve the quality of life of patients with CRS (according to the visual analog scale and all SNOT-22 domains) during a control survey after 3 months (p<0.001). Surgical treatment has a stronger impact on the quality of life, which is more noticeable in the influence on the domains "Rhinological symptoms", "Extranasal symptoms", "Ear/facial symptoms" (p<0.05). According to the domains "Psychological dysfunction", "Sleep dysfunction", surgical intervention had no advantages in affecting the quality of life, compared with taking azoximer bromide (p<0.05).

[Problems of polypragmasia and drug interaction in the treatment of uncomplicated acute rhinosinusitis]. / Problemy polipragmazii i lekarstvennogo vzaimodeistviya v terapii neoslozhnennogo ostrogo rinosinusita.

This publication discusses polypragmasia and drug interactions in the treatment of uncomplicated acute rhinosinusitis in children and adults. Treatment of rhinosinusitis on an outpatient basis in multimorbid patients may be accompanied by multiple prescriptions, which increases the risk of drug interactions. The article reflects the most significant inappropriate combinations of both medicines and biologically active additives, herbal preparations. The advantages of using drugs with proven effectiveness, in particular intranasal glucocorticosteroids, are considered.

Comparative real-world outcomes of dupilumab versus endoscopic sinus surgery in the treatment of severe CRSwNP patients.

INTRODUCTION: Management of severe chronic rhinosinusitis with nasal polyps (CRSwNP) has changed significantly in recent years, with different treatments now available including biologics and endoscopic sinus surgery (ESS), although there are still few comparative studies. We aimed to compare 1-year outcomes of patients with severe CRSwNP treated with dupilumab or ESS plus intranasal corticosteroids (INCS). METHODS: In this retrospective, real-life, observational, cohort study, we enrolled 101 patients with severe CRSwNP who were treated with INCS and either ESS (n = 49) or dupilumab (n = 52). The following outcomes were considered: nasal polyp score (NPS), Sino Nasal Outcome Test-22 (SNOT-22), visual analogue scale (VAS) for specific symptoms, Sniffin' Sticks identification test (SSIT), need for oral corticosteroids (OCS) and local eosinophilia detected by nasal cytology. RESULTS: ΔNPS was significantly higher in the surgery group up to 12 months when the difference with dupilumab group was no longer significant (ΔNPS: 4 vs. 4.1). ΔVAS rhinorrhoea, ΔVAS smell and ΔSNOT-22 were significantly higher in the dupilumab group at 12 months (p < .05). SSIT scores were significantly better in the dupilumab group starting from the first month of follow-up (p < .05). In the dupilumab group, only 6.1% of patients had detectable local eosinophilia compared to 57% in the surgery group alongside with a lower need for OCS (16.3% vs. 61%). CONCLUSIONS: Both dupilumab and ESS were effective in improving outcomes in patients with severe CRSwNP over 12 months. Nevertheless, patients treated with dupilumab had greater improvement in terms of SNOT-22, VAS rhinorrhoea, VAS smell and SSIT scores, with better control of local inflammation and less need for OCS.

Effectiveness and safety profile of mepolizumab in chronic rhinosinusitis with nasal polyps: Real life data in a tertiary care.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a type 2 pattern of inflammation. Mepolizumab was approved for the treatment of CRSwNP in 2021, it may be useful to evaluate its safety profile in a real-world setting. AIM: This work aimed to prospectively highlight the effectiveness and safety profile of Mepolizumab in patients with CRSwNP enrolled in the Otorhinolaryngology Unit of the University Hospital of Messina. METHODS: An observational cohort study was carried out considering all patients treated with Mepolizumab. A descriptive analysis was conducted reporting all demographic characteristics, endoscopic evaluations, and symptom conditions. RESULTS: A total of 30 patients were treated with Mepolizumab, one patient discontinued the treatment. A statistically significant reduction in the Sino-Nasal Outcome Tests-22 (SNOT-22) and nasal polyp score (NPS) was shown at the 6th and 12th months compared to baseline values (SNOT-22, -33 and - 43, p < 0.001 for both comparisons; NPS, 0 and - 1, p < 0.001 for both comparisons). The median (Q1-Q3) sniffin' sticks test score increased from 7 (6-8) at the 6th month to 11 (10-13) at the 12th month. Seven patients (24.1 %) reported pain at the injection site, accompanied by redness, warmth, and tenderness within the first 24 h post-injection with a median duration of three days from the onset. CONCLUSIONS: Given the optimal treatment response and the minimal adverse effects observed, clinicians should consider Mepolizumab a safe and effective treatment in CRSwNP patients. Further studies in real-life setting are necessary to better understand the long-term effects.

Study protocol: the biologics in severe chronic rhinosinusitis with nasal polyps survey.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of intranasal corticosteroids and short-term use of oral corticosteroids, in adjunct with saline solution rinses. Surgical management is proposed in patients who failed after medical treatment. In France, two biologics are reimbursed in case of severe uncontrolled CRSwNP despite medical treatment and endoscopic sinus surgery. Waiting for head-to-head biologics comparison, studies should report the efficacy and safety of biologics in large real-life cohorts. This study protocol describes the aims and methods of a prospective, observational, national, multicentric cohort of patients with CRSwNP treated with biologics. METHODS AND ANALYSIS: The BIOlogics in severe nasal POlyposis SurvEy is a French multicentre prospective observational cohort study. The main aim is to assess the efficacy and tolerance of biologics in patients with CRSwNP, with or without association with other type 2 diseases, and to determine the strategies in case of uncontrolled disease under biologics. Patients over 18 years old requiring biologics for CRSwNP in accordance with its marketing approval in France (ie, severe nasal polyposis, with lack of control under nasal corticosteroid, systemic corticosteroids and surgery) are invited to participate. Collected data include topical history of surgical procedures and biologics, medication and use of systemic corticosteroids, visual analogical scales for specific symptoms, Sino-Nasal Outcome Test-22 questionnaire, nasal polyp score, asthma control test, Lund-Mackay score on CT scan and IgE concentration and eosinophilic count on blood sample. TRIAL REGISTRATION: NCT05228041/DRI_2021/0030.

[Blood eosinophilia in patients with severe bronchial asthma and chronic polypous rhinosinusitis treated with dupilumab: A review].

Bronchial asthma and chronic polypous rhinosinusitis are diseases associated with a T2-inflammatory immune response. These nosologies can be combined, creating the preconditions for a more severe course of multimorbidity, requiring the use of genetic engineering biological therapy. Dupilumab is a monoclonal antibody that can specifically bind to the alpha subunit of the interleukin-4 receptor and block the action of interleukins 4 and 13, which play a key role in the development of T2 inflammation. Numerous studies have demonstrated the high effectiveness of this medicament. The use of dupilumab in some cases may be accompanied by an increase in eosinophils in the blood. This article presents scientific base and our own experience in treating patients with dupilumab-associated eosinophilia, in addition we describe an algorithm for examining this group of patients for the purpose of timely diagnosis of diseases such as eosinophilic granulomatosis with polyangiitis, eosinophilic pneumonia, etc. It should be noted that in the most cases eosinophilia during targeted therapy with dupilumab is temporary and does not cause clinical manifestations.

[Chronic rhinosinusitis with nasal polyps-extension of dupilumab treatment intervals]. / Chronische Rhinosinusitis mit nasalen Polypen ­ Verlängerung der Dupilumab-Therapieintervalle.

BACKGROUND: In patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab 300 mg every 2 weeks can completely resolve nasal polys, sinus disease, and symptoms. In this case, patients ask for de-escalation. Although trials have demonstrated recurrence after stopping the biologic at 24 weeks, reducing the dose of dupilumab to once every 4 weeks did not result in deterioration of control. An extension of the treatment intervals would, however, diverge from the approval text, and is currently not recommended. METHODS: The course of 29 patients with severe CRSwNP, type­2 inflammation-associated comorbidities, and an indication for biologic was retrospectively analyzed. After resolution of CRSwNP and symptoms under biweekly dupilumab 300 mg, the dupilumab interval had been prolonged individually, initially up to 4 weeks, thereafter up to 6 weeks, if applicable. Control was assessed via quality of life (22-item sinonasal outcome test, SNOT-22), nasal polyp score, and smell identification test (Sniffin' Sticks; Burghart Messtechnik, Holm, Germany). RESULTS: All patients showed an excellent improvement within the first 3 months. The dupilumab application interval was extended to 4 weeks after 7-31 months (median 13 months) and to 6 weeks (n = 9) after 17-35 months (median 23 months). No recurrent polyps or symptoms were subsequently observed. CONCLUSION: In case of maximal regression of polyps and discomfort, extension of dupilumab injection intervals to 4 and potentially 6 weeks is possible without clinical worsening. Further studies on de-escalation or termination of biologic treatment when CRSwNP control is achieved are essential.

Dupilumab's impact on nasal citology: Real life experience after 1 year of treatment.

BACKGROUND: Biologic agents are considered a new revolutionized therapy for severe and recurrent forms of CRSwNP which disease burden is not sufficiently controlled by conservative and/or surgical treatments. Recent Research has focused on evaluating their real-life efficacy in CRSwNP, as only limited reports on real-life data are available. However, in most studies, the response to treatment is evaluated in terms of improvement in Nasal Polyp Score (NPS) or in Sino-Nasal Outcome test (SNOT-22) scores. However, both criteria do not consider nasal immunophlogosis, which can be easily assessed by nasal cytology. The aim of our study was to evaluate changings in the nasal inflammatory infiltrate of CRSwNP patients treated with Dupilumab for 12 months. METHODS: 27 patients suffering from severe CRSwNP treated with Dupilumab were recruited. Nasal cytology findings, NPS, SNOT-22, ACT scores and blood eosinophil count at T0 (before treatment) and at T1 (after 1 year of treatment) were compared. RESULTS: After 1 year of biological therapy with Dupilumab, NPS, SNOT-22 and, among the 17 asthmatic patients, ACT scores improved significantly. At T1, a statistically significant percentage of patients showed negative citology. Moreover, a significant reduction in the mast cell-eosinophilic pattern and an increase of neutrophils and bacteria was reported. CONCLUSIONS: The response to treatment can be considered both in the case of negative nasal cytology and in the case of the appearance of neutrophils and bacteria. In this context, eosinophils, the specific target of biological therapies, play a crucial role in regulating tissue homeostasis and, consequently, the nasal immunophlogosis.

Dupilumab improves sleep quality in chronic rhinosinusitis with nasal polyps.

PURPOSE: Chronic rhinosinusitis with nasal polyps (CRSwNP) often alters sleep quality. Dupilumab emerged as an innovative and effective therapy for refractory/recurrent severe CRSwNP. The aim of this observational retrospective study was to evaluate the sleep quality in patients with CRSwNP who underwent treatment with dupilumab. MATERIALS AND METHODS: Forty-five patients treated with dupilumab for CRSwNP were enrolled. Clinical parameters (age, sex, comorbidities, Nasal Polyp Score - NPS, Asthma Control Test - ACT), nasal cytology, quality of life (Sino Nasal Outcome Test 22 - SNOT-22), sleep quality (Pittsburgh Sleep Quality Index - PSQI, Epworth Sleepiness Scale - ESS), and risk of sleep apnea (STOP-BANG) were recorded before treatment (T0), and after 3 (T1), 6 (T2), and 12 months (T3). RESULTS: NPS, ACT and SNOT-22 total score improved during treatment (p < 0.05). Meanwhile, all sleep parameters evaluated with SNOT-22, ESS and PSQI improved over time (p < 0.001), expect for PSQI Use of sleeping medications. Indeed, sleep drugs are rarely used before and during the treatment. The global sleep quality was classified as poor in 88.9 % of cases at T0 and decreased to 5.7 % at T3. A high risk of sleep apnea was revealed by the STOP-BANG in 68.9 % of cases at T0 and 2.8 % of patient at T3 (p < 0.001). CONCLUSIONS: Dupilumab improves the sleep quality and reduce the risk of sleep apnea in patients with severe CRSwNP. Its favorable effect occurs within 3 months and is maintained during the treatment.

Butyrate inhibits type 2 inflammation in eosinophilic chronic rhinosinusitis.

Butyrate and other Short-chain fatty acids (SCFAs) are microbial metabolites from Bacteroides and Clostridium species that may suppress type 2 inflammation. However, the mechanisms of SCFAs in the nasal sinuses are not fully understood. We aimed to clarify the in vitro and in vivo roles of SCFAs in eosinophilic chronic rhinosinusitis (ECRS) pathophysiology. We investigated whether SCFAs induced changes in type 2 cytokines, IgE, and apoptosis and the roles of GPR41, GPR43, and histone deacetylase. Analysis of the control subjects demonstrated that butyrate of SCFAs effectively inhibited type 2 cytokine production in PBMCs, ILC2s, and CD4+ T cells and IgE production in CD19+ B cells. In annexin V analysis, butyrate also induced late apoptosis of PBMCs. The butyrate-induced inhibition of type 2 cytokines appeared involved in histone deacetylase inhibition but not in GPR41 or GPR43. In an analysis of ECRS in humans, butyrate inhibited type 2 cytokine production in PBMCs and nasal polyp-derived cells. The butyrate concentration in nasal lavage fluid was significantly decreased in ECRS patients compared to controls and non-ECRS patients. Our findings confirm that butyrate can inhibit type 2 inflammation and may be a potential therapeutic target for ECRS.

Intranasal delivery of low-dose anti-CD124 antibody enhances treatment of chronic rhinosinusitis with nasal polyps.

Frequent injections of anti-CD124 monoclonal antibody (αCD124) over long periods of time are used to treat chronic rhinosinusitis with nasal polyps (CRSwNP). Needle-free, intranasal administration (i.n.) of αCD124 is expected to provide advantages of localized delivery, improved efficacy, and enhanced medication adherence. However, delivery barriers such as the mucus and epithelium in the nasal tissue impede penetration of αCD124. Herein, two novel protamine nanoconstructs: allyl glycidyl ether conjugated protamine (Nano-P) and polyamidoamine-linked protamine (Dendri-P) were synthesized and showed enhanced αCD124 penetration through multiple epithelial layers compared to protamine in mice. αCD124 was mixed with Nano-P or Dendri-P and then intranasally delivered for the treatment of severe CRSwNP in mice. Micro-CT and pathological changes in nasal turbinates showed that these two nano-formulations achieved ∼50 % and ∼40 % reductions in nasal polypoid lesions and eosinophil count, respectively. Both nano-formulations provided enhanced efficacy in suppressing nasal and systemic Immunoglobulin E (IgE) and nasal type 2 inflammatory biomarkers, such as interleukin 13 (IL-13) and IL-25. These effects were superior to those in the protamine formulation group and subcutaneous (s.c.) αCD124 given at a 12.5-fold higher dose. Intranasal delivery of protamine, Nano-P, or Dendri-P did not induce any measurable toxicities in mice.

Biologic Therapy in Pediatric Chronic Rhinosinusitis: A Systematic Review.

OBJECTIVE: Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP). DATA SOURCES: PubMed, MEDLINE, Cochrane, and clinical trial registries. REVIEW METHODS: Key search terms related to biologic therapy in pediatric CRSwNP were identified via a structured query of current medical literature and clinical trial databases. CONCLUSIONS: There is a dearth of active clinical trials and research studies for biologics targeting pediatric CRSwNP. There is an ongoing compassionate-use clinical trial involving Dupilumab for children with nasal polyps as well as only 1 published work specifically focused on Dupilumab for pediatric CRSwNP in the setting of aspirin-exacerbated respiratory disease. IMPLICATIONS FOR PRACTICE: For children with atopic dermatitis, asthma, and chronic idiopathic urticaria, biologic therapies such as Omalizumab, Dupilumab, and Mepolizumab have gained Food and Drug Administration approval. The role of biologic therapy in pediatric CRSwNP demonstrates significant promise in the comprehensive management of the unified airway. Additional Phase III trials are necessary to broaden clinical indications for children with comorbid conditions and complex sinonasal disease.

The Effectiveness of Biological Agents on Chronic Rhinosinusitis with Nasal Polyposis in Patients with Comorbid Asthma: A Multicenter Real-Life Study from Türkiye.

Background and Objectives: Real-life data on the efficacy of biologic agents (BAs) on asthma-comorbid CRSwNP are needed. Our primary goal is to investigate the effects of BAs on CRSwNP symptoms, as well as endoscopic and tomography scores. Our secondary goal is to show a reduction in the frequency of acute sinusitis exacerbations and the need for surgery. Materials and Methods: We conducted a multicenter, retrospective, real-life study. We screened the patients with asthma-comorbid CRSwNP treated with omalizumab or mepolizumab. A total of 69 patients (40 F/29 M; omalizumab n = 55, mepolizumab n = 14) were enrolled. We compared the visual analog scale (VAS), sinonasal outcome test-22 (SNOT-22), nasal congestion score (NCS), Lund-Mackay computed tomography score (LMS), and total endoscopic polyp scores (TPS) before and after BAs. We evaluated the endoscopic sinus surgery (ESS) and acute exacerbations of chronic rhinosinusitis (AECRS) frequencies separately, according to the BAs. Results: The overall median (min-max) age was 43 (21-69) years. The median (min-max) of biologic therapy duration was 35 (4-113) months for omalizumab and 13.5 (6-32) for mepolizumab. Significant improvements were seen in VAS, SNOT-22, and NCS with omalizumab and mepolizumab. A significant decrease was observed in TPS with omalizumab [95% CI: 0-4] (p < 0.001), but not with mepolizumab [95% CI: -0.5-2] (p = 0.335). The frequency of ESS and AECRS were significantly reduced with omalizumab [95% CI: 2-3] (p < 0.001) and [95% CI: 2-5] (p < 0.001); and mepolizumab [95% CI: 0-2] (p = 0.002) and [95% CI: 2-8.5] (p < 0.001), respectively. There was no significant difference in LMS with either of the BAs. Conclusions: Omalizumab and mepolizumab can provide a significant improvement in the sinonasal symptom scores. BAs are promising agents for CRSwNP patients with frequent exacerbations and multiple surgeries.

[Biologic therapy in patients with severe NSAID-exacerbated respiratory disease and previous aspirin desensitization : Results of a multicentric study]. / Biologikatherapie bei schwer erkrankten Patienten mit "NSAID-exacerbated respiratory disease" und stattgehabter ASS­Desaktivierung : Ergebnisse einer multizentrischen Studie.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type­2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on a multicenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD. METHODS: This is a retrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12 months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics. RESULTS: Treatment was commenced in 122 patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, B­SIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12 months of add-on therapy (p < 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4 cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control. CONCLUSION: Add-on biologic therapy is effective, safe, and widely accepted among CRSwNP + NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy.

[Difficult-to-treat chronic rhinosinusitis-when the standard treatment is not effective and biologics are not available]. / Schwierig zu behandelnde chronische Rhinosinusitis ­ wenn die Standardtherapie nicht wirkt und Biologika nicht zur Verfügung stehen.

BACKGROUND: In recent years, significant improvements have been made in the treatment options for uncontrolled chronic rhinosinusitis (CRS) refractory to standard medical and surgical therapy. This is the result of a better understanding of the pathophysiology and the resulting development of biologicals for CRS with nasal polyps (CRSwNP). However, biologics are not (yet) available for all patients in Europe. OBJECTIVE: Based on the session "Difficult-to-treat CRS, when biologics are not available" at the 29th Congress of the European Rhinologic Society (ERS) 2023 in Sofia, Bulgaria, the treatment options for uncontrolled CRS with the exclusion of biologics will be discussed. MATERIALS AND METHODS: The content of the presentations "Is there a place for antibiotics?" "Indications for revision surgery," "Novel systemic treatment options," "Novel local treatment options," and "Phototherapy for nasal polyps" are outlined and supported by a review of the literature. RESULTS: Various treatment options are available for managing uncontrolled CRS, even if biologic treatments are unavailable. Treatment options for type­2 (T2) CRS include steroid rinses, repeated short-term oral steroids, steroid-eluting stents, and extended sinus surgery. In the case of nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD), acetylsalicylic acid (ASA) desensitization can be considered. Non-T2 endotypes or CRS without nasal polyps (CRSsNP) may benefit from several weeks of macrolides and xylitol rinses. CONCLUSION: To accurately assess the efficacy of second-line therapies for treatment of difficult-to-treat CRS within an endotype-specific framework, additional controlled clinical trials are needed that take into account the heterogeneity of CRS endotypes.

The Inflation Reduction Act: Implications for Medicare spending and access to biologic therapies for chronic rhinosinusitis with nasal polyposis and asthma.

KEY POINTS: In 2021, Medicare spending on biologics was $926 million in Part B (FFS) and $1.3 billion in Part D (FFS/MA). Between 2017 and 2021, annual Medicare spending on biologics increased by approximately 200%. Between 2023 and 2025, Medicare Part D OOP costs for biologics will decrease by an estimated 50%-60%.