The 2025 American Academy of Allergy, Asthma, and Immunology (AAAAI) and World Allergy Organisation (WAO) Joint Congress was a pivotal event for advancing the field of respiratory medicine.1 Taking place from 25 February–3 March, in San Diego, CA, USA, the theme of this year’s congress was ‘Climate Change and Allergic Diseases: Global Impact on Health’, which was explored through interactive learning, new research and enlightening presentations. Among the most anticipated presentations were key abstracts focusing on chronic rhinosinusitis; these studies explored novel biologic therapies, genetic factors, and targeted treatments that could provide new approaches to managing chronic rhinosinusitis with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP), potentially improving patient outcomes.
Efficacy And Safety Of Tezepelumab In Adults With Severe Chronic Rhinosinusitis With Nasal Polyps: Results From The Phase 3 WAYPOINT Study
The Phase 3 WAYPOINT study (ClinicalTrials.gov identifier: NCT04851964) demonstrated that tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), significantly improved both symptoms and quality of life in adults with severe CRSwNP.2,3
In this randomized, double-blind, placebo-controlled trial, patients with severe CRSwNP were assigned 1:1 to receive 210 mg tezepelumab or placebo subcutaneously every 4 weeks for 52 weeks. The study evaluated primary endpoints, including change in total nasal polyp score (NPS) and bi-weekly mean nasal congestion score (NCS) at week 52. Secondary endpoints included self-reported loss of smell, Sino-nasal Outcome Test (SNOT-22) total score, Lund–Mackay score (LMK), total symptom score (TSS), and time-to-first nasal polyp (NP) surgery decision or systemic corticosteroid (SCS) treatment for CRSwNP.
At week 52, NPS improved by −2.101 (95% confidence interval [CI]: −2.414, −1.788) with tezepelumab compared with placebo (p<0.0001), while NCS improved by −1.088 (95% CI: −1.261, −0.915; p<0.0001). Improvements were observed as early as week 4 for NPS and week 2 for NCS (both p<0.01). At week 52, significant improvements (p<0.0001) with tezepelumab versus placebo were also seen in: loss of smell (−1.033 [−1.204, −0.863]); SNOT-22 score (−28.434 [−33.485, −23.383]); LMK (−5.392 [−6.098, −4.687]); and TSS (−7.235 [−8.365, −6.105]). Compared to placebo, tezepelumab reduced the need for NP surgery or SCS by 92% (hazard ratio: 0.08, 95% CI: 0.03, 0.17). Adverse events were similar between the tezepelumab and placebo groups.
Efficacy and Safety of Twice-Yearly Depemokimab in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP): The Phase III Randomized, Double-Blind, Placebo-Controlled Replicate ANCHOR-1/2 Trials
Depemokimab is the first investigational ultra-long-acting biologic engineered with enhanced interleukin-5 binding affinity, high potency, and an extended half-life. The Phase III ANCHOR-1 and 2 trials (ClinicalTrials.gov identifiers: NCT05274750/NCT05281523) evaluated the efficacy and safety of twice-yearly depemokimab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), compared to placebo.4-6 These were randomized, double-blind, placebo-controlled trials. Patients were randomized 1:1 to receive either depemokimab (ANCHOR-1/ANCHOR-2: N=143/N=129) or placebo (ANCHOR-1/ANCHOR-2: N=128/N=128), plus standard of care. Patients who received depemokimab were treated once every 26 weeks over 52 weeks and were evaluated for changes in nasal polyp score (NPS; range: 0–8) and mean nasal obstruction score (verbal response scale [VRS]; range: 0–3). Adverse events (AEs) and serious adverse events (SAEs) were also monitored.
The trials demonstrated that depemokimab significantly reduced the NPS compared with placebo at week 52 (treatment difference [95% CI]: ANCHOR-1, -0.7 [-1.1,-0.3], p<0.001; ANCHOR-2, -0.6 [-1.0,-0.2], p=0.004; integrated, -0.7 [-0.9,-0.4]). Depemokimab also improved mean nasal obstruction VRS over weeks 49–52 (treatment difference [95% CI]: ANCHOR-1, -0.23 [-0.46,0.00], p=0.047; ANCHOR-2, -0.25 [-0.46,-0.03], p=0.025; integrated, -0.24 [-0.39,-0.08]). Safety data indicated that similar proportions of depemokimab-treated patients experienced AEs/SAEs compared with those in the placebo group (AEs: ANCHOR-1, 74% versus 79%; ANCHOR-2, 76% versus 80%; SAEs: ANCHOR-1, 3% versus 5%; ANCHOR-2, 5% versus 8%).
Mepolizumab Improves Patient-Reported Outcomes and Reduces Treatment Burden in Patients With Chronic Rhinosinusitis With Nasal Polyps: A Real-World Chart Review Study
A real-world chart review study assessed the effectiveness of mepolizumab, an anti-interleukin-5 biologic, in improving patient-reported outcomes (PROs) in patients with CRSwNP.7 The study involved 64 physicians (38 allergists/immunologists and 26 otolaryngologists) providing data for 150 eligible patients (mean age: 44 years). The cohort had a median follow-up of 20.6 months, with common comorbidities including allergic rhinitis (55%) and asthma (51%). Data on symptom control, SNOT-22 scores, oral corticosteroid (OCS) use, and surgical interventions were collected before and after initiating mepolizumab treatment.
The study found significant improvements post-mepolizumab. The mean SNOT-22 score (a measure of symptom severity) decreased from 61 pre-mepolizumab to 28 post-mepolizumab (mean difference: -32 [95% CI: -35, -29] p<0.001). 89% of patients showed clinically significant improvement in SNOT-22 scores post-mepolizumab, defined as a mean difference ≥-8.95 using the lowest score post-mepolizumab. Oral corticosteroid use also significantly decreased, from 0.6 treatments per patient per year (PPPY) pre-mepolizumab to 0.3 PPPY post-mepolizumab (rate ratio: 0.46 [95% CI: 0.30-0.72] p<0.001). Median OCS bursts reduced from 1 pre-mepolizumab to 0 post-mepolizumab (p<0.001), and the mean cumulative OCS dose decreased from 766 mg to 256 mg (p<0.001). The rate of surgical interventions also reduced from 0.2 PPPY pre-treatment to 0.1 PPPY post-mepolizumab.
A Study of Dupilumab in Adults with CRSsNP: Results from the Liberty ORION study
The Liberty ORION study (ClinicalTrials.gov identifier: NCT04678856) assessed whether dupilumab, an interleukin-4 and -13 inhibitor, relieved CRSsNP signs and symptoms in patients with evidence of type 2 inflammation.8,9
Liberty ORION was a phase 2, double-blind trial conducted over 24–52 weeks. Adults with CRSsNP (irrespective of eosinophil level) were randomized 1:1 to receive either 300 mg dupilumab every 2 weeks or placebo. The primary endpoint was the change in Lund-Mackay CT (LMK-CT) score at week 24 in patients treated with dupilumab with eosinophils ≥300 cells/mm³. In patients with eosinophils ≥300 cells/mm³, secondary endpoints included: change in LMK-CT and sinus total symptom score (sTSS) from baseline to week 24 versus placebo. The exploratory endpoints were the University of Pennsylvania Smell Identification Test (UPSIT), and SNOT-22.Â
In patients with screening eosinophils ≥300 cells/mm³, dupilumab treatment resulted in a mean reduction of -6.63 (95% CI [-8.71, -4.54], P<0.0001) in LMK-CT score at week 24. At week 24, these patients showed mean differences when treated with dupilumab versus placebo (95% CI): LMK-CT score -5.95 (-8.38, -3.51); sTSS -1.43 (-3.28, 0.41); UPSIT 5.91 (-1.56, 13.38); and SNOT-22 -14.71 (-34.35, 4.94).
References
- 2025 AAAAI/WAO Joint Congress. Home page. Available at: https://annualmeeting.aaaai.org/ (accessed 26 March 2025).
- Han J, Lipworth B, Desrosiers M, et al. Efficacy And Safety Of Tezepelumab In Adults With Severe Chronic Rhinosinusitis With Nasal Polyps: Results From The Phase 3 WAYPOINT Study. J Allergy Clin Immunol. 2025;155(Suppl.):AB442.
- ClinicalTrials.gov. Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis (WAYPOINT). ClinicalTrials.gov identifier: NCT04851964. Available at: https://clinicaltrials.gov/study/NCT04851964 (accessed 26 March 2025).
- Han J, Cornet M, Mullol J, et al. Efficacy and Safety of Twice-Yearly Depemokimab in Patients With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP): The Phase III Randomized, Double-Blind, Placebo-Controlled Replicate ANCHOR-1/2 Trials. J Allergy Clin Immunol. 2025;155(Suppl.):AB443.Â
- ClinicalTrials.gov. Efficacy and Safety of Depemokimab (GSK3511294) in Participants With Chronic Rhinosinusitis With Nasal Polyps (ANCHOR-1). ClinicalTrials.gov identifier: NCT05274750. Available at: https://clinicaltrials.gov/study/NCT05274750 (accessed 26 March 2025).
- ClinicalTrials.gov. Efficacy and Safety of Depemokimab (GSK3511294) in Participants With Chronic Rhinosinusitis With Nasal Polyps (ANCHOR-2) (ANCHOR-2). ClinicalTrials.gov identifier: NCT05281523. Available at: https://clinicaltrials.gov/study/NCT05281523 (accessed 26 March 2025).
- Edgecomb A, Silver J, Hwee J, et al. Mepolizumab Improves Patient-Reported Outcomes and Reduces Treatment Burden in Patients With Chronic Rhinosinusitis With Nasal Polyps: A Real-World Chart Review Study. J Allergy Clin Immunol. 2025;155(Suppl.):AB448.Â
- Lee S, Luong A, Peters A, et al. A Study of Dupilumab in Adults with CRSsNP: Results from the Liberty ORION study. J Allergy Clin Immunol. 2025;155(Suppl.):AB76.
- ClinicalTrials.gov. Dupilumab in CRSsNP (Liberty CRSsNP). ClinicalTrials.gov identifier: NCT04678856. Available at: https://clinicaltrials.gov/study/NCT04678856 (accessed 26 March 2025).
Disclosure: This article was created by the touchRESPIRATORY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
Cite: #AAAAI2025: Must-know Updates in Chronic Rhinosinusitis – Key Data from the AAAAI/WAO Joint Congress. touchRESPIRATORY. March 26, 2025.
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