Estimating Clinically Meaningful Change of Efficacy Outcomes in Inadequately Controlled Chronic Rhinosinusitis with Nasal Polyposis

Joseph K Han; Claus Bachert; Stella E Lee; Claire Hopkins; Enrico Heffler; Peter W Hellings; Anju T Peters; Siddhesh Kamat; Diane Whalley; Shanshan Qin; Lauren Nelson; Shahid Siddiqui; Asif H Khan; Yongtao Li; Leda P Mannent; Isabelle Guillemin; Chien-Chia Chuang

doi:10.1002/lary.29888

Estimating Clinically Meaningful Change of Efficacy Outcomes in Inadequately Controlled Chronic Rhinosinusitis with Nasal Polyposis

Laryngoscope. 2022 Feb;132(2):265-271. doi: 10.1002/lary.29888. Epub 2021 Dec 1.

Authors

Joseph K Han¹, Claus Bachert^{2

3

4}, Stella E Lee⁵, Claire Hopkins⁶, Enrico Heffler⁷, Peter W Hellings^{2

8

9}, Anju T Peters¹⁰, Siddhesh Kamat¹¹, Diane Whalley¹², Shanshan Qin¹³, Lauren Nelson¹³, Shahid Siddiqui¹¹, Asif H Khan¹⁴, Yongtao Li¹⁵, Leda P Mannent¹⁶, Isabelle Guillemin¹⁷, Chien-Chia Chuang¹⁸

Affiliations

¹ Department of Otolaryngology & Head and Neck Surgery, Eastern Virginia Medical School, Norfolk, Virginia, U.S.A.
² Upper Airways Research Laboratory and Department of Otorhinolaryngology, Ghent University, Ghent, Belgium.
³ Division of ENT Diseases, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
⁴ First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁵ Division of Otolaryngology-Head & Neck Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.
⁶ Department of Otorhinolaryngology - Head and Neck Surgery, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
⁷ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
⁸ Department of Otorhinolaryngology - Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium.
⁹ Department of Otorhinolaryngology, Amsterdam University Medical Centres, Location AMC, Amsterdam, The Netherlands.
¹⁰ Allergy-Immunology Division and the Sinus and Allergy Center, Feinberg School of Medicine, Northwestern University, Evanston, Illinois, U.S.A.
¹¹ Medical Affairs, Regeneron Pharmaceuticals, Inc., Tarrytown, New York, U.S.A.
¹² Patient-Centered Outcome Assessment, RTI Health Solutions, Manchester, United Kingdom.
¹³ Patient-Centered Outcome Assessment, RTI Health Solutions, Research Triangle Park, North Carolina, U.S.A.
¹⁴ Global Medical Affairs, Sanofi, Chilly-Mazarin, France.
¹⁵ Global Medical Affairs Respiratory, Sanofi, Bridgewater, New Jersey, U.S.A.
¹⁶ Global Clinical Development, Sanofi, Chilly-Mazarin, France.
¹⁷ Patient Reported Outcomes, Sanofi, Lyon, France.
¹⁸ Health Economics and Value Assessment, Sanofi, Cambridge, Massachusetts, U.S.A.

Abstract

Objectives/hypothesis: Clinical trials of biologics to treat chronic rhinosinusitis with nasal polyposis (CRSwNP) have evaluated objective outcomes (e.g., University of Pennsylvania Smell Identification Test [UPSIT], nasal polyps score [NPS], and computed tomography Lund-Mackay score [CT-LMK]) and patient-reported symptoms (e.g., nasal congestion/obstruction [NC], loss of smell [LoS], and total symptom score [TSS]). We estimated anchor-based thresholds for clinically meaningful change in objective and patient-reported outcomes in patients with CRSwNP using data from LIBERTY NP SINUS-24 and SINUS-52 trials (NCT02912468; NCT02898454).

Methods: Target patient-reported outcomes were NC, LoS, and TSS; target objective outcomes were UPSIT, NPS, and CT-LMK. Anchor measures were the 22-item sinonasal outcome test (SNOT-22) rhinologic symptoms domain and total score and rhinosinusitis visual analog scale (VAS). The appropriateness of each anchor measure was evaluated by reviewing correlations between change in anchor measures and target outcomes and descriptive scores on target outcomes by levels of change in the anchor measure. Established thresholds for anchor measures (3.8 points for SNOT-22 rhinologic symptoms, 8.9 points for SNOT-22 total, 1-category improvement for rhinosinusitis VAS) were used to estimate clinically meaningful score changes for each target outcome.

Results: Based on correlations between change in anchor measures and target outcomes, SNOT-22 rhinologic symptoms domain was deemed the most appropriate anchor measure. Using this anchor measure, thresholds for clinically meaningful within-patient change were NC: 1 point; LoS: 1 point; TSS: 3 points; UPSIT: 8 points; NPS: 1 point; and CT-LMK: 5 points.

Conclusion: These thresholds support interpretation of efficacy results for target outcomes in CRSwNP trials.

Level of evidence: 2 Laryngoscope, 132:265-271, 2022.

Keywords: Adult rhinology; nose and paranasal sinuses; quality of life.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biological Products / therapeutic use*
Chronic Disease
Humans
Nasal Polyps / complications
Nasal Polyps / drug therapy*
Patient Reported Outcome Measures*
Rhinitis / complications
Rhinitis / drug therapy*
Sinusitis / complications
Sinusitis / drug therapy*
Treatment Outcome

Substances

Biological Products

Associated data

ClinicalTrials.gov/NCT02912468
ClinicalTrials.gov/NCT02898454