Jérôme Msihid

Summary: Asthma is underdiagnosed and undertreated in China, where treatment with dupilumab could be beneficial. In this industry‐funded post hoc exploratory analysis, dupilumab showed clinical efficacy in allergic and non‐allergic asthma.

The Atopic Dermatitis Control Tool (ADCT) is a validated six-item tool used in clinical trials to assess eczema control in adolescents and adults. Two versions of the ADCT were recently developed using a US Food and Drug Administration-recommended methodology. One is intended for use with caregivers of children aged 6 months to 11 years (the Caregiver ADCT; score range 0–24; higher scores indicate worse control; recall period the past 7 days). The other, the Child Eczema Control Tool (ECT), is intended for use with children aged 8 to 11 years. We conducted the first psychometric validation of the Caregiver ADCT (first 100 caregivers recruited), which demonstrated no floor or ceiling effects in response distributions, except for a floor effect for ‘sleep-trouble nights’ (47% selected the least severe option; n = 47/100). There were strong inter-item correlations (r ≥ 0.57; P < 0.001) and construct validity (r ≥ 0.59; P < 0.001), consistent with a priori hypotheses. The Caregiver ADCT showed strong internal consistency (Cronbach’s α = 0.92, 95% confidence interval 0.90–0.94). A score ≥ 7 was identified as the optimal threshold for identifying children whose eczema was ‘not in control’.

Purpose: The EuroQoL-five dimensions-three levels (EQ-5D-3L) utility values vary across regions, hence become non-interchangeable. This study details a methodology to adjust EQ-5D-3L utility values from the published United States (US) scores for use in the United Kingdom (UK) when individual-level patient data (IPD) are inaccessible. Methods: Linear and polynomial regression models were fitted to map the US-derived EQ-5D-3L health state utility weights (HSUWs) into UK values. Model fit was evaluated via visual inspection and coefficient of determination (R²). The best-fit model was used to develop a utility-adjustment algorithm. Data for external validation of the algorithm were collected through a targeted literature review, which identified studies reporting mean EQ-5D-3L utilities from both the US and UK. The coefficients of the best-fit model were validated against the published mean US and UK utilities, and the algorithm was validated by comparing published and predicted mean UK utilities. Results: The linear model confirmed linearity between US and UK HSUWs, and was the best-fit over the polynomial model, both visually and with R² (0.9574 vs 0.9576). Eleven publications (N = 93,625 participants) reporting the mean US and UK EQ-5D-3L utilities based on the valuation of EQ-5D-3L responses were included for validation. The linearity between the published mean US and UK EQ-5D-3L utilities was deemed valid (R² = 0.9955) with similar slopes (1.45 vs 1.39) and intercepts (− 0.43 vs − 0.38) between the linear model and the published utility-based line. The algorithm (Utility^UK = [− 0.3813 + 1.3904 × Utility^US]) predicted the mean UK utilities, which marginally differed from the reported mean UK utilities, confirming its validity. Conclusion: A robust method was developed to adjust US-derived EQ-5D-3L utilities and reflect UK preferences. This method helps predict and transpose utilities from the literature across countries as a supporting tool when IPD are unavailable, which is necessary when adapting cost-effectiveness models to different settings.

Loss of sense of smell is a cardinal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP) and significantly impacts health-related quality of life. Dupilumab significantly improved smell outcomes (loss of smell [LoS] score; University of Pennsylvania Smell Identification Test [UPSIT]) versus placebo in the phase 3 SINUS-24/-52 studies (clinicaltrials.gov, NCT02898454/NCT02912468) in patients with severe CRSwNP. This post hoc analysis investigated the effect of dupilumab on olfaction using UPSIT smell impairment categories. Patients with baseline smell impairment (UPSIT ≤34/≤33 [women/men; score range 0-40] AND LoS score ≥1 [0-3] AND smell/taste item of the 22-item Sinonasal Outcome Test >0 [SNOT-22; 0-5]) treated with dupilumab 300 mg or placebo once every 2 weeks on background intranasal corticosteroids were analyzed. Of 724 patients, 665 (91.9%) had smell impairment at baseline; most had anosmia (UPSIT 0-18) (dupilumab/placebo: 80.9%/79.8%). At Week 24, the proportion of dupilumab-treated patients with anosmia decreased to 28.5%, while 14.9% achieved normosmia; most placebo-group patients (79.2%) remained anosmic and only 1.2% achieved normosmia (odds ratio: 17.3 [95% confidence interval: 5.1, 59.0]; p<.0001); results were similar at Week 52. Improvements in Nasal Polyps Score, nasal congestion, and SNOT-22 total score were moderately correlated with improvements in UPSIT at Weeks 24 and 52 (r = -0.38 to -0.50). Most patients with severe CRSwNP had anosmia at baseline. Dupilumab treatment significantly improved smell versus placebo, with 14.9% achieving normosmia by Week 24. There was a trend for better clinical outcomes in patients with greater smell improvement.

Aim: The impact of complete bilateral nasal obstruction [nasal polyp score (NPS) = 8/8] on treatment outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. This post hoc analysis assessed disease burden and dupilumab efficacy in patients with severe CRSwNP and baseline NPS = 8 in SINUS-24/-52 (NCT02912468/NCT02898454). Methods: Efficacy outcomes assessed: NPS, peak nasal inspiratory flow (PNIF), Lund-Mackay computed tomography (LMK-CT), nasal congestion/obstruction (NC), loss of smell (LoS), rhinosinusitis visual analog scale (rhino-VAS), University of Pennsylvania Smell Identification Test (UPSIT), 22-item Sinonasal Outcome Test (SNOT-22) in patients receiving dupilumab 300 mg or placebo every 2 weeks. Responder analyses evaluated clinically meaningful improvements [≥ 1 (NPS, NC, LoS); ≥ 5 (LMK-CT); ≥ 8 (UPSIT); ≥ 8.9 (SNOT-22); ≥ 20 L/min (PNIF)]. Results: Ninety-eight patients were included [59% prior NP surgery, 84% systemic corticosteroids (SCS) use in the previous 2 years, 60% coexisting asthma, 91% anosmic, 97% impaired nasal airflow]. Least squares (LS) mean differences [dupilumab vs. placebo (95% CI)] in change from baseline at week (W) 24: NPS, −2.04 (−2.67, −1.40); PNIF, 65.9 (39.4, 92.4) L/min; LMK-CT, −4.97 (−6.50, −3.44); NC, −1.30 (−1.72, −0.89); LoS, −0.96 (−1.39, −0.54); Rhino-VAS, −3.37 (−4.67, −2.07); UPSIT, 8.55 (4.91, 12.20); SNOT-22, −25.3 (−34.1, −16.4) (all P < 0.0001). For all outcomes, significantly greater proportions of dupilumab vs. placebo patients achieved clinically meaningful improvements at W24. Fewer dupilumab vs. placebo patients required SCS and/or surgery through W24 (11.8% vs. 36.7%; P = 0.0005). Efficacy outcomes were similar at W52 (SINUS-52; n = 39) with P values vs. placebo of < 0.0001 for NPS and NC; 0.0002 for LMK-CT; 0.0031 for LoS; 0.0014 for rhino-VAS; 0.0013 for UPSIT; 0.0012 for SNOT-22. Conclusions: In patients with CRSwNP with complete bilateral nasal obstruction, dupilumab treatment resulted in clinically significant improvements in NPS, LMK-CT, PNIF, symptoms, and health-related quality of life.

Rhee CK, et al. Allergy Asthma Immunol Res. 2024 Jul;16(4):372-386. https://doi.org/10.4168/aair.2024.16.4.372

Objectives: To assess the severity of the top 5 22‐item Sino‐Nasal Outcome Test (SNOT‐22) items ranked most important by patients with chronic rhinosinusitis with nasal polyps (CRSwNP), the effect of dupilumab on these items, and their association with objective disease measures.Study Design: Post hoc analysis of the SINUS‐24 (NCT02912468) and SINUS‐52 (NCT02898454) clinical trials.Setting: Multinational, multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group studies.Methods: Patients ranked the SNOT‐22 items most affecting their health at baseline. Item symptom severity (0‐5 scale) was assessed at baseline, Week 24 (W24), and Week 52 (W52). Changes in nasal polyps score (NPS) and Lund–Mackay (LMK) scores were assessed in patients with/without SNOT‐22 items improvements of at least 1 severity group point at W24 and W52.Results: The SNOT‐22 items ranked most important at baseline were “decreased sense of smell/taste” (87% of patients), followed by “nasal blockage” (82%), “postnasal discharge” (40%), “thick nasal discharge” (37%), and “wake up at night” (26%); 82%, 61%, 32%, 40%, and 26% of patients reported severe symptoms (score 4 or 5) for these items, respectively. Dupilumab improved score severity for all top 5 items versus placebo at W24 and W52. Improvements in NPS and LMK scores were numerically greater in patients with improvements in the SNOT‐22 top 5 items.Conclusion: Loss of smell/taste was ranked as the most important symptom by patients with CRSwNP. Dupilumab reduced the severity of the top 5 most important SNOT‐22 items versus placebo, in parallel with improvements in objective disease measures.Clinical Trial Registration: SINUS‐24 and SINUS‐52 clinical trials were registered with ClinicalTrials.gov, identifiers NCT02912468 and NCT02898454, respectively.