Dupilumab Group Research Articles

Differential Nasal Recolonization and Microbial Profiles in Chronic Rhinosinusitis With Nasal Polyps Patients After Endoscopic Sinus Surgery or Dupilumab Treatment: A Prospective Observational Study.

The role of microbial profiles in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) pathogenesis is increasingly recognised, with microbial imbalances perpetuating inflammation. We performed this study to associate the different nasal microbiological profile changes with the response to surgical or monoclonal treatment. This prospective observational study evaluated changes in the nasal microbial profiles of 44 patients (22 dupilumab, 22 surgery) over 6 months. Clinical assessments were performed at baseline and follow-ups, including Sino-Nasal Outcome Test-22 (SNOT-22) scores and Sniffin Sticks-Identification (SS-I) olfactory testing. Microbial profiling of nasal swabs was carried out by microbial culture and subsequent molecular identification by Polymerase chain reaction (PCR) and sequencing. Baseline characteristics of 44 patients (22 dupilumab, 22 surgery) enrolled in this study were similar between groups. In the dupilumab group, Staphylococcus epidermidis prevalence rose from 37.03% to 59.25%, while Pseudomonas aeruginosa was eradicated. Moreover, dupilumab stabilised Staphylococcus aureus at 63.64%, while its prevalence increased in the surgery group (from 22.72% to 50%). When bacterial groups were associated with clinical scores, P. aeruginosa carriers had worse SNOT-22 (21.00 ± 1.41) and SS-I (5.50 ± 0.71) scores. Instead, S. epidermidis-colonised patients exhibited significantly lower mean SNOT-22 (15.39 ± 8.54) and greater SS-I scores (8.39 ± 3.77). The best outcomes were found in the subgroup of S. epidermidis carriers undergoing the dupilumab treatment. The two treatments modulated the microbial profiles differently, and, most importantly, clinical responses might depend on the association between treatment and the dominant bacterial species colonising the nasal cavity. Further investigation into microbial-restorative strategies could enhance outcomes for better treatment of CRS.

Perioperative adjuvant therapy with short course of dupilumab with ESS for recurrent CRSwNP.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a high rate of disease recurrence following endoscopic sinus surgery (ESS). Type 2 disease is associated with a higher incidence of recurrence and is believed to impact disease resolution via interference with epithelial healing and pathogen immunity. We wished to verify if perioperative control of Type 2 inflammation with an anti-IL4/IL13 targeting monoclonal antibody and during the resolution period following surgery leads to better control of the disease long term. In this prospective, placebo-controlled, double-blinded trial. Thirty adult subjects with recurrent CRSwNP underwent ESS plus or minus 14 weeks of perioperative dupilumab, initiated 4 weeks (two injections) pre-ESS. Subjective and objective parameters of nasal patency, olfaction, quality of life (QoL), and adverse events were monitored up to 52 weeks post-ESS. Microbiological culture was performed to characterize pathogens colonization under both conditions. ESS safely improved subjective and objective measures of nasal patency, olfaction, and QoL in both groups. Olfaction was conserved longer in the dupilumab-treated group, with 33.3% of subjects presenting anosmia at 12 months after ESS in the dupilumab group compared to 50.0% with placebo. This was associated with persistent decreases in serum IgE, which were not seen with placebo treatment. No unusual safety signals were observed. Short-course adjuvant perioperative treatment with dupilumab is associated with improved long-term olfactory outcomes and persistent lowering of serum IgE.

Short- and long-term cost-effectiveness of abrocitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis in China

Background Biologics and JAK inhibitors were the most effective innovative systemic treatments for moderate-to-severe atopic dermatitis (AD). However, their cost-effectiveness in China remains unclear. This study aims to compare both the short- and long-term cost-effectiveness of abrocitinib and dupilumab in adults with moderate-to-severe AD from the perspective of the Chinese healthcare system. Methods A hybrid decision tree and Markov model were developed to simulate the costs and health outcomes of interventions on both short-term and long-term horizons. Short- and long-term horizons were employed to reflect the 26-week induction treatment and model the extended 10-year maintenance treatment period, respectively. The cost-effectiveness of strategies was measured by incremental cost-effectiveness ratios (ICERs), which were then compared with the willingness-to-pay threshold (WTP) that was equivalent to the gross domestic product (GDP) per capita of China in 2023 ($12,681 [€11,679.26]). One-way and probabilistic sensitivity analyses were conducted to validate the robustness of the model. Results Over the short-term horizon, the QALYs (quality-adjusted life years) gained were 0.43 for the abrocitinib group and 0.42 for the dupilumab group, with the costs being $2,716.01 (€2,501.46) and $3,940.33 (€3,629.06), respectively. Over the long-time horizon, abrocitinib therapy yields higher QALYs (6.60 versus 6.53) and incurs a lower cost ($22,765.15 [€20,966.81] versus $30,683.38 [€28,259.54]) compared to dupilumab. The probability of abrocitinib being cost-effective was nearly 100% under the current WTP. Both short- and long-term results showed that abrocitinib was more effective and less costly than dupilumab, making abrocitinib the dominant option. Conclusions Abrocitinib was dominant compared to dupilumab both over the short- and long-term horizon for moderate-to-severe AD in China. Future research incorporating real-world evidence and long-term efficacy outcomes could further refine these economic evaluations.

Influence of Single Nucleotide Polymorphisms on CRS Outcomes: A Preliminary Observational Study.

To conduct a preliminary investigation into the relationship between specific SNP variants, type II inflammation, and the effectiveness of dupilumab therapy and surgery in patients with CRS. In this prospective study, 48 subjects were enrolled, comprising 32 CRS patients and 16 healthy controls. The CRS patients were subjected to either dupilumab therapy or endoscopic surgery according to EPOS guidelines. SNP variants were identified using the TaqMan SNP genotyping technique. The identified SNP profiles were compared between the control group and CRS patients, and their potential influence on treatment outcomes was evaluated. Treatment responses were assessed based on symptom scores, such as SS-I, SNOT-22, disease progression using the NPS findings, and SNP profiles at a 6-month follow-up. The primary measures included the Nasal Polyp Score, Smell Identification Test (SIT) score, and SNOT-22 outcomes. Dupilumab therapy and surgery significantly decreased NPS, with the last showing superior results. However, dupilumab therapy resulted in a significantly improved SIT score. Significant differences were observed in SNP profiles, particularly with rs1800629 (TNFA), rs2856838 (IL1a), rs17561 (IL1a), and rs1805011 (IL4R). In particular, the expression of rs2856838 and rs1805011 variants in the dupilumab group was associated with significantly better SIT and SNOT-22 outcomes than non-expressors. Also, the surgery group patients expressing the rs2856838 variant reported significant improvements in SNOT-22 scores. These preliminary findings suggest that SNP genotypes may guide personalized treatment strategies for CRS. Further larger prospective studies are required to confirm these initial observations. 2 Laryngoscope, 2024.

Comparative Effectiveness of Dupilumab Versus Sinus Surgery for Chronic Rhinosinusitis With Polyps: Systematic Review and a Meta-Analysis.

Current treatment paradigms recommend surgical intervention when conventional medical management proves ineffective in resolving chronic rhinosinusitis with nasal polyposis. To assess and compare the efficacy of dupilumab and functional endoscopic sinus surgery (FESS) for the treatment of chronic rhinosinusitis with nasal polyp (CRSwNP) over time. Studies comparing CRSwNP patients who received dupilumab with those who underwent FESS were included. Outcome measures included the nasal congestion score (NCS), Sino-nasal Outcome Test-22 (SNOT-22), University of Pennsylvania Smell Identification Test-40 (UPSIT-40), and nasal polyp score (NPS). The risk of bias was evaluated using the Newcastle-Ottawa Scale. A total of 4 studies with 724 participants were included. The dupilumab group had a superior NCS, but an inferior NPS, compared to the FESS group during the follow-up period. The SNOT-22 score of the dupilumab group was inferior to that of the FESS group until 6 months posttreatment, but the scores were similar at around 1 year. A similar trend was observed for the UPSIT-40 score, but the score of the dupilumab group was higher at around 1 year. Functional endoscopic sinus surgery was more effective than dupilumab for several months after treatment. However, at 1 year after treatment, the effects of the 2 treatments became similar, with greater olfactory improvement seen in the dupilumab group.

Dupilumab Improves Health-Related Quality of Life and a Range of Symptoms in Patients With Eosinophilic Esophagitis.

Improvements in symptomatic experience and health-related quality of life (HRQoL) are among the most important treatment benefits in patients with eosinophilic esophagitis (EoE). We assessed the impact of dupilumab treatment on HRQoL, patients' impression of dysphagia, and symptoms beyond dysphagia in adults/adolescents (≥12 years) with EoE in parts A and B of the LIBERTY EoE TREET (NCT03633617) study. The EoE Symptom Questionnaire (EoE-SQ; frequency and severity of nondysphagia symptoms), EoE Impact Questionnaire (impact of EoE on HRQoL), and Patient Global Impression of Severity and Patient Global Impression of Change of dysphagia were used to assess the efficacy of weekly dupilumab 300 mg vs placebo. At week 24, dupilumab reduced EoE-SQ Frequency (least squares mean difference vs placebo [95% confidence interval] part A -1.7 [-2.9, -0.5], part B -1.4 [-2.3, -0.5]; both P < 0.01) and EoE-SQ Severity (part A -2.0 [-3.9, 0.0], P < 0.05, part B -1.5 [-3.0, 0.1], P = 0.07) overall scores, and improved scores across all individual items. Improvement in the dupilumab group was clinically meaningful to patients. Dupilumab also meaningfully improved EoE Impact Questionnaire average scores and improved individual item scores at week 24, particularly emotional and sleep disturbance. More dupilumab-treated patients reported improvement in the Patient Global Impression of Change of dysphagia vs placebo or reported having no symptoms per the Patient Global Impression of Severity of dysphagia at week 24. Dupilumab reduced the impact of EoE on multiple aspects of HRQoL, patients' impression of dysphagia, and frequency and severity of symptoms beyond dysphagia in adults/adolescents with EoE.

Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age

BackgroundDupilumab is a human monoclonal antibody that blocks interleukin-4 and interleukin-13 pathways and has shown efficacy in five different atopic diseases marked by type 2 inflammation, including eosinophilic esophagitis in adults and adolescents.MethodsIn this phase 3 trial, we randomly assigned, in a 2:2:1:1 ratio, patients 1 to 11 years of age with active eosinophilic esophagitis who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups) (Part A). At the end of Part A, eligible patients in each dupilumab group continued the same regimen and those in the placebo groups were assigned to higher-exposure or lower-exposure dupilumab for 36 weeks (Part B). At each level of exposure, dupilumab was administered in one of four doses tiered according to baseline body weight. The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤6 per high-power field) at week 16. Key secondary end points were tested hierarchically.ResultsIn Part A, histologic remission occurred in 25 of the 37 patients (68%) in the higher-exposure group, in 18 of the 31 patients (58%) in the lower-exposure group, and in 1 of the 34 patients (3%) in the placebo group (difference between the higher-exposure regimen and placebo, 65 percentage points [95% confidence interval {CI}, 48 to 81; P<0.001]; difference between the lower-exposure regimen and placebo, 55 percentage points [95% CI, 37 to 73; P<0.001]). The higher-exposure dupilumab regimen led to significant improvements in histologic, endoscopic, and transcriptomic measures as compared with placebo. The improvements in histologic, endoscopic, and transcriptomic measures between baseline and week 52 in all the patients were generally similar to the improvements between baseline and week 16 in the patients who received dupilumab in Part A. In Part A, the incidence of coronavirus disease 2019, nausea, injection-site pain, and headache was at least 10 percentage points higher among the patients who received dupilumab (at either dose) than among those who received placebo. Serious adverse events were reported in 3 patients who received dupilumab during Part A and in 6 patients overall during Part B.ConclusionsDupilumab resulted in histologic remission in a significantly higher percentage of children with eosinophilic esophagitis than placebo. The higher-exposure dupilumab regimen also led to improvements in measures of key secondary end points as compared with placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; EoE KIDS ClinicalTrials.gov number, NCT04394351.)

Dupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation

BackgroundDupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation, has shown efficacy and safety in a phase 3 trial involving patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation and an elevated risk of exacerbation. Whether the findings would be confirmed in a second phase 3 trial was unclear.MethodsIn a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of 300 cells per microliter or higher to receive subcutaneous dupilumab (300 mg) or placebo every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations. Key secondary end points, analyzed in a hierarchical manner to adjust for multiplicity, included the changes from baseline in the prebronchodilator forced expiratory volume in 1 second (FEV1) at weeks 12 and 52 and in the St. George’s Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better quality of life) total score at week 52.ResultsA total of 935 patients underwent randomization: 470 were assigned to the dupilumab group and 465 to the placebo group. As prespecified, the primary analysis was performed after a positive interim analysis and included all available data for the 935 participants, 721 of whom were included in the analysis at week 52. The annualized rate of moderate or severe exacerbations was 0.86 (95% confidence interval [CI], 0.70 to 1.06) with dupilumab and 1.30 (95% CI, 1.05 to 1.60) with placebo; the rate ratio as compared with placebo was 0.66 (95% CI, 0.54 to 0.82; P<0.001). The prebronchodilator FEV1 increased from baseline to week 12 with dupilumab (least-squares mean change, 139 ml [95% CI, 105 to 173]) as compared with placebo (least-squares mean change, 57 ml [95% CI, 23 to 91]), with a significant least-squares mean difference at week 12 of 82 ml (P<0.001) and at week 52 of 62 ml (P=0.02). No significant between-group difference was observed in the change in SGRQ scores from baseline to 52 weeks. The incidence of adverse events was similar in the two groups and consistent with the established profile of dupilumab.ConclusionsIn patients with COPD and type 2 inflammation as indicated by elevated blood eosinophil counts, dupilumab was associated with fewer exacerbations and better lung function than placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; NOTUS ClinicalTrials.gov number, NCT04456673.)

Comparative real-world outcomes of dupilumab versus endoscopic sinus surgery in the treatment of severe CRSwNP patients.

Management of severe chronic rhinosinusitis with nasal polyps (CRSwNP) has changed significantly in recent years, with different treatments now available including biologics and endoscopic sinus surgery (ESS), although there are still few comparative studies. We aimed to compare 1-year outcomes of patients with severe CRSwNP treated with dupilumab or ESS plus intranasal corticosteroids (INCS). In this retrospective, real-life, observational, cohort study, we enrolled 101 patients with severe CRSwNP who were treated with INCS and either ESS (n = 49) or dupilumab (n = 52). The following outcomes were considered: nasal polyp score (NPS), Sino Nasal Outcome Test-22 (SNOT-22), visual analogue scale (VAS) for specific symptoms, Sniffin' Sticks identification test (SSIT), need for oral corticosteroids (OCS) and local eosinophilia detected by nasal cytology. ΔNPS was significantly higher in the surgery group up to 12 months when the difference with dupilumab group was no longer significant (ΔNPS: 4 vs. 4.1). ΔVAS rhinorrhoea, ΔVAS smell and ΔSNOT-22 were significantly higher in the dupilumab group at 12 months (p < .05). SSIT scores were significantly better in the dupilumab group starting from the first month of follow-up (p < .05). In the dupilumab group, only 6.1% of patients had detectable local eosinophilia compared to 57% in the surgery group alongside with a lower need for OCS (16.3% vs. 61%). Both dupilumab and ESS were effective in improving outcomes in patients with severe CRSwNP over 12 months. Nevertheless, patients treated with dupilumab had greater improvement in terms of SNOT-22, VAS rhinorrhoea, VAS smell and SSIT scores, with better control of local inflammation and less need for OCS.

Dupilumab Reduces Exacerbations Independent of Changes in Biomarkers in Moderate-to-Severe Asthma

Changes from baseline in fractional exhaled nitric oxide (FeNO) and blood eosinophil count (Eos) may be related to efficacy outcomes in dupilumab-treated patients with moderate-to-severe asthma. This post hoc analysis investigated biomarker changes in placebo- and dupilumab-treated patients with uncontrolled moderate-to-severe asthma enrolled in QUEST (NCT02414854). Spline analyses of annualized severe exacerbation rate (AER) and change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) at week 52 were performed as a function of the fold change in FeNO at week 52 and the maximum fold change in Eos over weeks 0-12 (also change from baseline in pre-BD FEV1 at week 12). The combined placebo and dupilumab groups comprised 638 and 1264 patients, respectively. FeNO levels declined rapidly by week 2 and then gradually to week 52 in patients treated with dupilumab versus placebo; Eos, after initially increasing with dupilumab, declined slightly from baseline in both treatment groups. AER during QUEST showed no significant association with the change in biomarkers in either treatment group. The change from baseline in pre-BD FEV1 at week 52 was inversely associated with the fold change in FeNO in both groups, with a significant difference between the dupilumab and placebo curves (P= .014), and was positively associated with the fold change in Eos in both groups (P= .022). Relative changes in FeNO and Eos were not associated with AER, regardless of treatment arm. However, changes in both biomarkers showed a predictive value for lung function improvement; for FeNO, this was specific to the dupilumab treatment arm.

A206 DUPILUMAB TREATMENT REDUCES THE FREQUENCY OF DYSPHAGIA DAYS AND ACTIONS TO RELIEVE DYSPHAGIA IN PATIENTS WITH EOSINOPHILIC ESOPHAGITIS (EOE): RESULTS FROM THE PHASE 3 LIBERTY EOE TREET STUDY

Abstract Background Dysphagia is the predominant symptom of EoE in adolescents and adults. Aims To assess change in number of days with dysphagia, number of days with action taken to relieve dysphagia, and change in pain associated with dysphagia in patients receiving dupilumab 300 mg once weekly (qw) vs placebo in LIBERTY EoE TREET. Methods Dysphagia Symptom Questionnaire (DSQ) score (range 0–84) was calculated from daily responses over 14 days for Q2 (frequency) and Q3 (severity); Q4 (pain) was separately assessed (range 0–56). Higher scores indicate a worse outcome. Inclusion criteria required patients to have a baseline DSQ score ≥10. Number of days with dysphagia (Q2), action taken to relieve dysphagia (Q3), and pain (Q4) were analyzed at baseline and Week (W) 24 for the placebo-controlled study parts (A and B). P-values are nominal. Results 81 patients enrolled in Part A (dupilumab/placebo: n=42/39) and 159 in Part B (n=80/79). Mean number of days with dysphagia was similar with dupilumab vs placebo at baseline, but lower in the dupilumab group at W24 (Figure). Mean [SD] change from baseline (dupilumab vs placebo) was –6.5 [3.78] vs –3.9 [4.61], Pampersand:003C0.05 in Part A, and –7.8 [4.24] vs –4.7 [4.02], Pampersand:003C0.0001 in Part B. Mean [SD] number of days with any action taken to relieve dysphagia was similar in the dupilumab vs placebo group at baseline (Part A: 7.3 [3.76] vs 8.2 [3.82]; Part B: 9.5 [3.53] vs 8.7 [3.85]) but lower (numerically) in the dupilumab group at W24 (Part A: 3.6 [3.73] vs 5.7 [4.78]; Part B: 3.0 [3.84] vs 5.3 [4.69]). At W24, numerically fewer days with more severe dysphagia (need to cough/gag, vomit, or seek medical attention to relieve dysphagia) occurred with dupilumab vs placebo. Baseline DSQ pain score was similar in dupilumab vs placebo groups. Least squares mean [95% CI] change from baseline at W24 in DSQ pain score was −10.1 [–12.2, –7.9] vs −4.4 [–6.8, –2.0] for dupilumab vs placebo in Part A (difference vs placebo: −5.7 [95% CI −8.67, –2.72]; P=0.0002), and −10.0 [–11.7, –8.1] vs −6.5 [–8.3, –4.6] in Part B (difference vs placebo: −3.5 [95% CI −5.90, −1.03]; P=0.0053). Conclusions At W24, patients in the dupilumab 300 mg qw group experienced fewer days with dysphagia, fewer days with any action taken for dysphagia relief, and less pain associated with dysphagia vs placebo. Funding Agencies Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.

A213 DUPILUMAB EFFICACY IN EOSINOPHILIC ESOPHAGITIS PERSISTS FOR HISTOLOGIC, SYMPTOMATIC, AND ENDOSCOPIC OUTCOMES REGARDLESS OF CONCOMITANT HIGH-DOSE PROTON PUMP INHIBITOR USE

Abstract Background Proton-pump inhibitor (PPI) therapy is the most commonly used first-line therapy for eosinophilic esophagitis (EoE) but data informing long-term outcomes are limited. Aims This pre-specified analysis of data from the phase 3 LIBERTY EoE TREET (NCT03633617) study assessed the efficacy of weekly dupilumab vs placebo in patients (pts) with and without concomitant PPI use. Methods Pts with peak intraepithelial eosinophil (eos) count ≥15 eos/high-power field (hpf) after ≥8 weeks’ high-dose PPI were randomized to dupilumab or placebo. Pts on high-dose PPIs at screening remained on a high-dose regimen during the treatment period; switching of PPI types was permitted but new initiation of PPIs was prohibited. Endpoints at Week 24 were: proportion of pts achieving ≤6 eos/hpf, absolute change from baseline in Dysphagia Symptom Questionnaire (DSQ) score, % change in peak eos count, absolute change in Endoscopic Reference Score (EREFS) and Histologic Scoring System (HSS) grade/stage scores. Results In Parts A and B, respectively, 61.9% and 71.3% of pts in the dupilumab group and 64.1% and 72.2% in the placebo group were using PPIs at randomization. For pts treated with dupilumab vs placebo in Parts A and B, respectively, ≤6 eos/hpf was achieved by 69.2% (95% confidence interval [CI] 48.2–85.7) vs 8.0% (95% CI 1.0–26.0) and 59.6% (95% CI 45.8–72.4) vs 7.0% (95% CI 2.0–17.0) of pts using PPIs, and by 43.8% (95% CI 19.8–70.1) vs 0% (95% CI 0–23.2) and 56.5% (95% CI 34.5–76.8) vs 4.5% (95% CI 0.1–22.8) of pts not using PPIs. Least squares mean change from baseline in DSQ score for dupilumab vs placebo was –18.5 vs –12.9 and –21.8 vs –14.0 for pts using PPIs in Parts A and B, respectively, and –27.8 vs –3.8 and –28.4 vs –13.3 for those not using PPIs (Figure 1). Dupilumab improved outcomes vs placebo for secondary endpoints, with comparable results in pts with and without concomitant PPI use. Absolute change from baseline in EREFS score is shown in Figure 1. Dupilumab was generally well tolerated. Conclusions Dupilumab improved histologic, symptomatic, and endoscopic aspects of EoE in adults and adolescents, up to 24 weeks, regardless of concomitant high-dose PPI use. Figure 1. Effect of dupilumab 300 mg qw versus placebo on primary endpoints (A) proportion of patients with peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf (B) absolute change from baseline in DSQ total score at Week 24 (C) absolute change from baseline in EREFS total score at Week 24, by concomitant PPI use CI, confidence interval; DSQ, Dysphagia Symptom Questionnaire; EREFS, endoscopic reference score; eos, eosinophils; hpf, high-power field; LS, least squares; PPI, proton pump inhibitor; pt, patient; qw, once weekly; SE, standard error. Funding Agencies Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.

A204 DUPILUMAB IMPROVES HISTOLOGIC, ENDOSCOPIC, AND SYMPTOMATIC ASPECTS OF EOSINOPHILIC ESOPHAGITIS IN PATIENTS AGES 1–ampersand:003C12 YEARS

Abstract Background Dupilumab is approved in Canada for eosinophilic esophagitis (EoE) in patients (pts) aged ≥12 years who weigh ≥40 kg; no treatments are approved for pts aged ampersand:003C12 years. Aims The Phase 3 EoE KIDS trial evaluated dupilumab efficacy and safety vs placebo (PBO) in pts aged 1–ampersand:003C12 years with EoE. Methods Part A was a 16-week (W) PBO-controlled study; pts were randomized 2:2:1:1 to weight-tiered dupilumab on a higher-exposure (HE) or lower-exposure (LE) regimen, or PBO (2 groups) to W16. In Part B, pts continued dupilumab, or switched from PBO to dupilumab (HE/LE), to W52. Results At W16 (Part A), the HE dupilumab group had an improved proportion of pts achieving peak esophageal intraepithelial eosinophil count (PEC) ≤6 eosinophils/high-power field (hpf) vs PBO (67.6% vs 2.9%, Pampersand:003C0.0001; primary endpoint). At W52 (Part B), 62.9% of HE dupilumab/dupilumab pts, and 52.9% of PBO/HE dupilumab pts, achieved PEC ≤6. At W16, the following improved with HE dupilumab vs PBO: EoE-Histologic Scoring System grade and stage scores (–0.88 vs +0.02 and –0.84 vs +0.05, respectively, both Pampersand:003C0.0001); EoE-Endoscopic Reference Score (–3.5 vs +0.3, Pampersand:003C0.0001); overall caregiver assessed EoE status (global impression of change mean [SD], 2.1 [1.2] vs 3.3 [1.4]; lower scores represent more improvement). Improvements were maintained with continuous dupilumab and improved in PBO/dupilumab pts at W52. LE dupilumab maintained similar improvements achieved through W52; however, effects were generally either comparable or numerically lower with LE dupilumab vs HE dupilumab. At W16, COVID-19, rash, headache, and injection-site erythema occurred more frequently in patients receiving dupilumab, with higher incidence than PBO; AEs were similar through W52. Conclusions HE dupilumab met the primary endpoint of PEC ≤6 eos/hpf vs PBO, demonstrated significant changes in histologic and endoscopic aspects of EoE, and improved symptoms with benefits maintained/increased to W52. Funding Agencies Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.

510 - Dupilumab is efficacious in patients with prurigo nodularis regardless of stable use of topical corticosteroids and topical calcineurin inhibitors: pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Abstract Introduction Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by severely itchy skin nodules, which substantially affects quality of life. Although topical treatments are frequently prescribed, these therapies are limited by insufficient demonstrated evidence for efficacy, and/or associated side effects. Objectives This study reports the effect of dupilumab on pruritus, skin lesions, and quality of life in patients with PN, with or without stable use of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI), in an analysis of pooled data from two phase 3 trials. Materials &amp; Methods LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) were two randomized, double-blind, placebo-controlled, 24-week studies. Adults with PN inadequately controlled by topical prescription therapies, or for whom those therapies are inadvisable, were randomized 1:1 to dupilumab 300 mg every 2 weeks or matched placebo. “Stable use” was defined as maintaining the same medicine (low-to-medium potency TCS and/or TCI) during the study, with the same frequency of treatment (once or twice daily) as from 2 weeks prior to screening. Efficacy was assessed from baseline to Week 24 through the Worst Itch Numerical Rating Scale (WI-NRS; scored 0–10; high scores represent a poorer outcome), and the Investigator’s Global Assessment for PN-Stage score (IGA PN-S; scored 0–4; high scores represent a poorer outcome). Impact on Health-Related Quality of Life (HRQoL) was assessed through the Dermatology Life Quality Index questionnaire (DLQI; 10 questions scored 0–3 with a maximum score of 30; high scores represent poorer HRQoL). Results 311 patients were randomized (dupilumab/placebo n = 153/158), including 182 patients with stable use of TCI/TCS (dupilumab/placebo N = 91/91) and 129 patients without (dupilumab/placebo N = 62/67). Baseline demographics and disease characteristics were well balanced in both subgroups. At Week 24, significantly more patients treated with dupilumab with or without stable use of TCI/TCS achieved a ≥ 4-point improvement in WI-NRS (59.3%/58.1%) vs placebo (13.2%/26.9% [nominal P &amp;lt; 0.0001/P &amp;lt; 0.0001]). The proportion of patients achieving an IGA PN-S score of 0 or 1 at Week 24 was also significantly higher in the dupilumab group for patients with or without stable use of TCI/TCS (48.4%/43.5%), vs placebo (11.0%/25.4% [nominal P &amp;lt; 0.0001/P = 0.0319]). The positive impact of dupilumab treatment on HRQoL was greater, for patients with and without a stable use of TCI/TCS vs placebo, as suggested by the mean change from baseline in DLQI at Week 24 (−12.9/−11.9 vs −5.5/−7.1 [nominal P &amp;lt; 0.0001/P &amp;lt; 0.0001], respectively). Although the placebo response was higher for patients without stable use of TCI/TCS, the effect of dupilumab treatment was comparable in the two subgroups. Treatment-emergent adverse events (TEAEs) occurred with similar rates in dupilumab-treated patients with or without stable use of TCI/TCS (59.3%/60.7%), compared with placebo (53.3%/47.8%). Patients with or without stable use of TCI/TCS had similar rates of severe TEAEs in the dupilumab groups (2.2%/4.9%) and placebo groups (3.3%/4.5%). Conclusion Dupilumab treatment improves itch, skin lesions, and quality of life in patients with PN, with an acceptable safety profile, with little to no influence from concomitant treatment with topical therapies (TCI/TCS).

Differences in asthma-related outcomes by anti-IL-5 biologics, omalizumab, and dupilumab based on blood eosinophil counts.

Selecting optimal biologics based on type 2 biomarkers has been of interest in severe asthma treatment. However, few direct biomarker stratification-based comparisons have been made. To compare the effectiveness of anti-IL-5 (mepolizumab, benralizumab), omalizumab, and dupilumab in reducing the number of hospitalizations from asthma and exacerbations across all and eosinophil-stratified subgroups. A retrospective cohort study using the National Hospital Organization database (2016-2020) was performed. Asthmatic patients using biologics were selected, and the baseline backgrounds of the groups were balanced using inverse probability treatment weighting for propensity scores. Weighted rate ratios (RRs) were obtained using a Poisson regression model. Among the 320 patients with asthma using biologics, 205 (64.1%), 75 (23.4%), and 40 (12.5%) were categorized into the anti-IL-5, omalizumab, and dupilumab groups, respectively. After weighting, there were 47.1, 30.0, and 62.6 hospitalizations per 100 person-years [omalizumab vs. anti-IL-5: weighted RR, 0.61 (0.34-1.08); dupilumab vs. anti-IL-5: 1.48 (0.81-2.72)], and 117.0, 134.6, and 287.3 exacerbations per 100 person-years [omalizumab vs. anti-IL-5: 1.13 (0.83-1.54); dupilumab vs. anti-IL-5: 2.69 (1.91-3.78)] in these respective groups. In patients with eosinophil of ≥ 300/μL, the dupilumab group had more exacerbations compared with the anti-IL-5 group [weighted RR, 2.85 (1.82-4.46)]. In patients with eosinophil of < 300/μL, the omalizumab group had fewer hospitalizations compared with the anti-IL-5 group [weighted RR, 0.32 (0.13-0.51)]. Anti-IL-5 biologics may be more effective than dupilumab in patients with high blood eosinophil counts, while less effective than omalizumab in patients with low eosinophil counts.

Real-World Effectiveness of Biologics in Patients With Severe Asthma: Analysis of the KoSAR.

Severe asthma is associated with high morbidity and healthcare utilization; however, treatment options for these patients are limited. This study aimed to determine the therapeutic effects of biologics in clinical practice. This multicenter, retrospective cohort study included 136 patients who received biologics for at least 4 months between September 2017 and July 2022 at 25 medical centers affiliated with the Korean Severe Asthma Registry (KoSAR). The study evaluated the treatment effects, including acute exacerbation rates, maintenance of oral corticosteroid dosages, lung function, quality of life, blood eosinophil count, and fractional exhaled nitric oxide (FeNO) levels, by comparing measurements before and after 4 months of biologic treatment. Responses for each medication was evaluated based on the Global Evaluation of Treatment Effectiveness score, and any adverse reactions were summarized. With the administration of biologics over the course of 4 months, there was a reduction in asthma acute exacerbations, a significant improvement in lung function, and a significant decrease in daily maintenance dose of oral steroid. Blood eosinophil counts decreased in the mepolizumab and reslizumab groups, while FeNO levels decreased only in the dupilumab group. The Asthma Control Test, Quality of Life Questionnaire for Adult Korean Asthmatics, and the EuroQol-visual analogue scale scores showed a significant improvement. Most patients (80.15%) responded to the biologic treatment. Meanwhile, non-responders often had chronic rhinosinusitis as a comorbidity, exhibited lower lung function, and required higher doses of oral steroids. No severe adverse events were reported. Biologics are highly effective in Korean patients with Type 2 severe asthma, significantly reducing acute exacerbation rates and doses of oral corticosteroids, while also improving lung function. Therefore, it seems beneficial to administer biologics without any restrictions to patients exhibiting Type 2 severe asthma.

Dupilumab demonstrated efficacy and was well tolerated regardless of prior use of swallowed topical corticosteroids in adolescent and adult patients with eosinophilic oesophagitis: a subgroup analysis of the phase 3 LIBERTY EoE TREET study

ObjectiveTo assess the effect of long-term dupilumab on histological, symptomatic and endoscopic aspects of eosinophilic oesophagitis (EoE) in adolescent and adult patients with and without prior use of swallowed topical...

Prospective direct comparison of biologic treatments for severe eosinophilic asthma: Findings from the PRISM study

BackgroundAlthough various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy. ObjectiveTo compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA. MethodsThis was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time. ResultsA total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group. ConclusionIn patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period. Trial RegistrationThe cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939).

Direct comparative study of the effectiveness of mepolizumab and dupilumab in patients with severe non-allergic eosinophilic asthma

Introduction. Biologics for severe asthma (SA) treatment are widely used in real clinical practice. But there are very few direct comparative studies at the moment.Aim. To compare mepolizumab and dupilumab effectiveness in patients with non-allergic eosinophilic SA in real clinical practice using regional register of Sverdlovsk region.Materials and methods. The data of patients with non-allergic eosinophilic SA treated with dupilumab (n = 23) and mepolizumab (n = 19) were analyzed. Therapy effectiveness was determined according to BARS and patients’ proportion who achieved asthma remission, dynamics of ACT, AQLQ, FEV1, blood eosinophils, frequency of short-acting bronchodilators use and systemic glucocorticosteroids (SGCS) demand, frequency of asthma exacerbations and hospitalizations.Results. Within 12 months of targeted therapy a good response to biologics according to BARS in 77.8% of patients on dupilumab and in 82.4% of patients on mepolizumab (p = 1.000) was revealed. Remission of SA (without FEV1) was achieved in 62.5% of patients in dupilumab group and in 68.8% of patients in mepolizumab group (p = 1.000). Remission of SA (with FEV1) was achieved in 43.8% of patients on dupilumab and in 56.2% of patients on mepolizumab (p = 0.724). There were statistically significant improvements for all separately analyzed indicators in each observation group. Statistically significant differences after a year of therapy between groups were recorded in terms of eosinophil levels (p &lt; 0.001) and nasal symptoms assessed using the SNOT-22 questionnaire (p = 0.048) in favour of mepolizumab.Conclusions. Patients with non-allergic eosinophilic SA have good response to both dupilumab and mepolizumab. The drugs equally improve disease control, life quality, reduce the need for relievers and SGCS, show a similar safety level.

Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial

Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial