Otolaryngology Commons^™

Differences In Biologic Clinical Trials For Chronic Rhinosinusitis With Nasal Polyps—Are We Comparing Apples With Oranges?, Marjolein Cornet, Peter W. Hellings, Martin Desrosiers, Martin Wagenmann, Richard Follows, Laura Walrave, Luz Adriana Jimenez, Lee Tombs, Dawn Edwards, Peter Howarth, Joseph K. Han

Department of Otolaryngology (ENT) Faculty Publications

In recent years, several biologics targeting Type 2 inflammation have been developed for treating chronic rhinosinusitis with nasal polyps (CRSwNP). These have been studied in registrational randomized controlled trials (RCTs), which vary in their patient populations, trial design, endpoints, geography, timing, or data-handling processes. While (in)direct treatment comparisons and meta-analyses have been carried out to compare efficacy results from RCTs, often these fail to properly account for these between-study differences. Here, we summarize the key between-study differences that can influence trial outcomes and highlight the resulting challenges faced when comparing outcomes from different Phase III RCTs of biologics in CRSwNP.

Reply To: S. N. Katkuri Et Al. And H. Liu Et Al. On Early And Sustained Improvements In Sense Of Smell With Tezepelumab Treatment In Patients With Chronic Rhinosinusitis With Nasal Polyps (Waypoint), Joaquim Mullol, Joseph K. Han, Tanya M. Laidlaw, Claire Hopkins, Anju T. Peters, Oliver Pfaar, Martin Desrosiers, Stella E. Lee, Andrew P. Lane, Claudia Chen, Yun Chon, Sandhia S. Ponnarambil, Andrew Foster, Andrew W. Lindsley, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

[Introduction] We thank Dr. S. N. Katkuri, Dr. H. Liu, and their coauthors [1, 2] for their interest in our recent publication describing the improvements in loss of smell symptoms with tezepelumab versus placebo in patients with uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) in the WAYPOINT trial (NCT04851964) [3]. We are grateful for the authors' feedback on the clinical significance of the data presented and their appreciation of the consistency observed across a range of baseline clinical characteristic and demographic subgroups.

Use Of Tezepelumab For Chronic Rhinosinusitis With Nasal Polyps By Eosinophilic Endotype: Waypoint Post-Hoc Analysis, Shigeharu Fujieda, Nobuyoshi Otori, Joseph K. Han, Tadataka Yabuta, Claudia Chen, Claudio Marchese, Andrews Foster, Sandhia S. Ponnarambil, Yun Chan, Brian J. Lipworth

Department of Otolaryngology (ENT) Faculty Publications

Background

The phase 3 WAYPOINT study (NCT04851964) reported that tezepelumab improved outcomes in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), including nasal polyp size, nasal congestion, and sinonasal symptoms, and reduced the need for surgery and systemic corticosteroids (SCS).

Objective

To evaluate the efficacy and safety of tezepelumab across Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis-defined eosinophilic chronic rhinosinusitis (ECRS) subgroups.

Methods

Adults with severe CRSwNP were randomized to tezepelumab 210 mg or placebo every 4 weeks. Coprimary end points were the change from baseline to week 52 in total Nasal Polyp Score and the biweekly mean Nasal …

Medication Utilization For Patients With Chronic Rhinosinusitis With Nasal Polyposis (Crswnp) And Asthma In 12 Months Pre- And Post-Dupilumab Initiation, Emily Garvey, Bita Naimi, Alexander Duffy, Chase Kahn, Douglas Farquhar, Marc Rosen, Mindy Rabinowitz, Damaris Pena Evertz, Jessica Most, Elina Toskala, Gurston G. Nyquist

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Key Points:

• This study examines the impact of dupilumab on medication use for chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma patients.
• Patients on dupilumab had a reduction in oral/inhaled/topical steroids, antibiotics, and leukotriene receptor antagonists (LTRAs).
• The reduction in medication use had no impact on total polyp or SNOT-22 scores.

Benefits Of Immunoglobulin (Ig) Replacement Therapy For Primary And Secondary Immunodeficiency In Chronic Rhinosinusitis, Emily A. Garvey, Keisha Arielle Best, Bita Naimi, Alexander Duffy, Paavali Hannikainen, Chase Kahn, Douglas Farquhar, Marc Rosen, Mindy Rabinowitz, Shirley Fung, Elina Toskala, Gurston Nyquist

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

This is the first study to examine chronic rhinosinusitis (CRS) outcomes after starting immunoglobulin (Ig) replacement therapy for patients with primary (PID) and secondary immunodeficiency (SID). This is a retrospective review of patients diagnosed with CRS from 2018 to 2022 prior to initiating Ig therapy for the treatment of PID or SID. Outcomes included medication use and Sinonasal Outcome Test (SNOT-22) scores. Ten patients met the inclusion criteria. PID and SID patients had a decrease in antibiotics (PID: 9.40 to 3.20, P = .05, SID: 8.20 to 2.00, P = .04) and steroids (PID: (5.40 to 0.60; P = .06; …

The Value Of Multiple Medication Trials Prior To Balloon Sinuplasty In The Management Of Chronic Sinonasal Disease, Anand G. Shah, Macaulay Ojeaga, Josephine Novak, Vincent Honrubia

School of Medicine Publications

Introduction In patients with chronic rhinosinusitis, conservative interventions with extended medical trials are often attempted prior to procedural treatment. Balloon sinuplasty (BSP) is an established procedure for symptomatic relief from chronic rhinosinusitis. However, data suggesting the suboptimal efficacy of prolonged medication management trials, prior to BSP, is lacking.

Objectives The purpose of this study was to evaluate the efficacy of prolonged medication management trials, prior to BSP, for patients with chronic rhinosinusitis.

Methods A retrospective review was performed for all adults with chronic rhinosinusitis who received extended medical management prior to their BSP at two outpatient clinics, from November 1, …

Stat6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis And Asthma, A Model Of Unified Airway Disease, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Faculty, Staff and Student Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …

Stat6 Suppression Prevents Bleomycin-Induced Dermal Fibrosis, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Faculty, Staff and Student Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …

Guidance For Contemporary Use Of Biologics In Management Of Chronic Rhinosinusitis With Nasal Polyps: Discussion From A National Institutes Of Health-Sponsored Workshop, Lauren T Roland, Timothy L Smith, Rodney J Schlosser, Zachary M Soler, Anju T Peters, Tanya M Laidlaw, Benjamin S Bleier, Vijay Ramakrishnan, Elina Toskala, David W Kennedy, Amber U Luong

Faculty, Staff and Student Publications

BACKGROUND: Biologic medications are emerging as options for treating chronic rhinosinusitis with nasal polyps (CRSwNP). Several questions remain regarding patient selection, indications, clinical efficacy, and cost effectiveness.

METHODS: In November 2019, a group of physicians and scientists gathered to consider strategies for future studies regarding biologics. During the discussion, gaps in knowledge highlighted a need for a consensus on the present day use of biologics in polyp patients.

RESULTS: The goal of this guideline is to propose recommendations for the current use of biologics in CRSwNP as new evidence continues to emerge and inform practice.

CONCLUSION: We suggest that physicians …

Microbiotyping The Sinonasal Microbiome, Ahmed Bassiouni, Sathish Paramasivan, Arron Shiffer, Matthew R Dillon, Emily K Cope, Clare Cooksley, Mahnaz Ramezanpour, Sophia Moraitis, Mohammad Javed Ali, Benjamin S Bleier, Claudio Callejas, Marjolein E Cornet, Richard G Douglas, Daniel Dutra, Christos Georgalas, Richard J Harvey, Peter H Hwang, Amber U Luong, Rodney J Schlosser, Pongsakorn Tantilipikorn, Marc A Tewfik, Sarah Vreugde, Peter-John Wormald, J Gregory Caporaso, Alkis J Psaltis

Faculty, Staff and Student Publications

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal “microbiotypes” or “states”: the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based …

Can Symptoms Differentiate Between Chronic Adenoiditis And Chronic Rhinosinusitis In Pediatric Patients, Phillip R. Purnell, Jad H. Ramadan, Hassan H. Ramadan

Faculty & Staff Scholarship

The purpose of this article is to differentiate pediatric patients with chronic adenoiditis from those with chronic rhinosinusitis (CRS) based on presenting symptoms. A chart review from a tertiary care facility with pediatric patients who presented with suspected CRS from 2006 to 2014 was identified. We compared patient characteristics, clinical symptoms, duration of symptoms, and past medial history using univariate and multivariate logistic regression models. Based on recent literature, utilizing the computed tomography (CT) score, we identified those children with CRS versus those with chronic adenoiditis. Of the 99 pediatric patients included, 22 patients had diagnosis of adenoiditis and 77 …

Quality Of Life After Functional Endoscopic Sinus Surgery In Patients With Chronic Rhinosinusitis, Sadaf Qadeer, Shabbir Akhtar, Montasir Junaid, Muhammad Sohail Halim

Section of Otolaryngology, Head & Neck Surgery

Chronic Rhinosinusitis (CRS) is a group of disorders characterized by the inflammation of mucosa of the nasal passages and paranasal sinuses. It includes chronic rhinosinusitis with polyps, CRS without polyps and Allergic Fungal Sinusitis (AFS). This debilitating disease causes negative impact on quality of life (QOL) of patients. Functional endoscopic sinus surgery (FESS) is the mainstay of surgical treatment for patients and improves QOL of patients. This subjective assessment of QOL can be measured by disease specific questionnaires. SNOT-22 questionnaire is widely used and validated questionnaire for this purpose. Prospective study was done on 54 patients. Data were collected using …