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.
| Original language | English |
|---|---|
| Pages (from-to) | 265-271 |
| Number of pages | 7 |
| Journal | Laryngoscope |
| Volume | 132 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2022 |
Keywords
- Adult rhinology
- nose and paranasal sinuses
- quality of life
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Estimating Clinically Meaningful Change of Efficacy Outcomes in Inadequately Controlled Chronic Rhinosinusitis with Nasal Polyposis. / Han, Joseph K.; Bachert, Claus; Lee, Stella E. et al.
In: Laryngoscope, Vol. 132, No. 2, 02.2022, p. 265-271.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Estimating Clinically Meaningful Change of Efficacy Outcomes in Inadequately Controlled Chronic Rhinosinusitis with Nasal Polyposis
AU - Han, Joseph K.
AU - Bachert, Claus
AU - Lee, Stella E.
AU - Hopkins, Claire
AU - Heffler, Enrico
AU - Hellings, Peter W.
AU - Peters, Anju T.
AU - Kamat, Siddhesh
AU - Whalley, Diane
AU - Qin, Shanshan
AU - Nelson, Lauren
AU - Siddiqui, Shahid
AU - Khan, Asif H.
AU - Li, Yongtao
AU - Mannent, Leda P.
AU - Guillemin, Isabelle
AU - Chuang, Chien-Chia
N1 - Funding Information: j.k.h., c.b., s.e.l., c.h., e.h., p.w.h., a.t.p., s.s., y.l., l.p.m., and i.g.: provided interpretation of data and critical feedback, and final approval for submission. s.k., a.h.k., and c-c.c.: contributed to the conception and design of the study, provided interpretation of data and critical feedback, and final approval for submission. d.w., s.q., and l.n.: contributed to the conception and design of the study, acquired data, provided interpretation of data and critical feedback, and final approval for submission. Authors affiliated with Regeneron Pharmaceuticals, Inc. and Sanofi participated in the analysis and interpretation of data, writing of the report, and the decision to submit the manuscript for publication. In conclusion, our study examined the relationship between scores of the symptoms e-diary for CRSwNP (evaluating NC, LoS, anterior rhinorrhea, and posterior rhinorrhea), UPSIT, NPS, and CT-LMK and those from 2 widely used and validated outcome measures, the SNOT-22 and rhinosinusitis VAS, and the results were used to estimate thresholds for clinically meaningful within-patient improvement on the target outcomes. The estimated thresholds add to the psychometric literature for these measures and provide reference evidence for future CRSwNP trials to support interpretation of efficacy results obtained using these target outcomes. j.k.h., c.b., s.e.l., c.h., e.h., p.w.h., a.t.p., s.s., y.l., l.p.m., and i.g.: provided interpretation of data and critical feedback, and final approval for submission. s.k., a.h.k., and c-c.c.: contributed to the conception and design of the study, provided interpretation of data and critical feedback, and final approval for submission. d.w., s.q., and l.n.: contributed to the conception and design of the study, acquired data, provided interpretation of data and critical feedback, and final approval for submission. Authors affiliated with Regeneron Pharmaceuticals, Inc. and Sanofi participated in the analysis and interpretation of data, writing of the report, and the decision to submit the manuscript for publication. Patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) frequently experience nasal symptoms, including nasal congestion/obstruction (NC), loss of smell (LoS), and rhinorrhea.1,2 The high level of symptom burden associated with CRSwNP can impair patients' health-related quality of life (HRQoL).3?5 In addition, CRSwNP often occurs with other inflammatory conditions, with up to 67% of patients with CRSwNP also having asthma.1,6?9 Several biologic treatments, including dupilumab, omalizumab, mepolizumab, and benralizumab, are being evaluated or have been evaluated in randomized controlled trials (RCTs) among patients with uncontrolled CRSwNP despite prior use of steroids or sinus surgery.10?20 RCTs of biologics include objective endpoints such as the University of Pennsylvania Smell Identification Test (UPSIT), the nasal polyps score (NPS), and the computed tomography Lund-Mackay score (CT-LMK), as well as patient-reported endpoints such as NC, LoS, and total symptom score (TSS).21 In the context of the populations of patients with CRSwNP that are enrolled in such RCTs, no well-defined thresholds exist to infer clinical meaningfulness of within-patient change in scores for objective and patient-reported treatment outcomes. The threshold of meaningful within-patient change in a clinical outcome measure, often called responder definition, is defined as ?a score change in a measure, experienced by an individual patient over a predetermined time period that has been demonstrated in the target population to have a significant treatment benefit.? The goal of this analysis was to estimate thresholds for clinically meaningful within-patient change in objective and patient-reported endpoints in patients with CRSwNP, using data from the LIBERTY NP SINUS-24 and SINUS-52 RCTs (NCT02912468 and NCT02898454).10 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). Funding Information: The analyses of data from the LIBERTY NP SINUS‐24 and SINUS‐52 trials (NCT02912468; NCT02898454) described here were sponsored by Regeneron Pharmaceuticals, Inc. and Sanofi. Funding for medical writing assistance with this manuscript was provided by Regeneron Pharmaceuticals, Inc. and Sanofi. Publisher Copyright: © 2021 Sanofi Genzyme and RTI Health Solutions. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - Adult rhinology
KW - nose and paranasal sinuses
KW - quality of life
UR - http://www.scopus.com/inward/record.url?scp=85120445040&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/lary.29888
DO - https://doi.org/10.1002/lary.29888
M3 - Article
C2 - 34850966
VL - 132
SP - 265
EP - 271
JO - The Laryngoscope
JF - The Laryngoscope
SN - 0023-852X
IS - 2
ER -