Efficacy Of Dupilumab Research Articles

Dupilumab Efficacy and Safety in Severe Atopic Dermatitis in Children under 6 Years of Age: Two Clinical Cases

Background. Atopic dermatitis (AD) manifests during the first year of life in majority of all cases. The early disease onset is associated with the development of comorbid atopic conditions within the «atopic march» phenomenon. The AD pathogenesis is associated with genetic predisposition, epidermal barrier dysfunction, and immune dysregulation. T2-inflammation specifically determines the entire immune cascade of inflammatory reactions, and, thus, dictates the need of early drug intervention to modify the disease course. Clinical case description. This article presents two clinical cases of severe AD in children under 6 years of age. The treatment of both cases included genetically engineered biologic drug dupilumab. Continuous therapy for 4–5 months made it possible to relieve the skin manifestations of the disease.Conclusion. AD, manifesting in infancy, is associated with high risk of developing other atopic spectrum diseases in older age. The timely onset of biological therapy allows us to affect immune dysregulation, and thereby to prevent the comorbid atopic conditions development.

Long-term efficacy and safety of dupilumab for severe bullous pemphigoid: A prospective cohort study

BackgroundBullous pemphigoid (BP) is a common subepidermal bullous disease. Dupilumab is a novel treatment for BP. However, its long-term efficacy and safety have not been demonstrated in prospective studies. ObjectiveEvaluate the long-term efficacy and safety of dupilumab in treating severe BP. MethodsPatients were divided into two groups: the methylprednisolone monotherapy group (M), and the methylprednisolone and dupilumab combination therapy group (D + M). This study consisted of two stages. The first stage focused on the initial treatment phase, where the early efficacy and safety was evaluated. The study then entered the 12-month maintenance treatment stage, where we assessed recurrence in both groups. Additionally, we evaluated the rate of healing of skin lesions, glucocorticoids burden and length of hospital stay and various laboratory test indicators. ResultsAfter four weeks of treatment, the Bullous Pemphigoid Disease Area Index (BPDAI) and pruritus Numerical Rating Scale scores of the D + M group decreased significantly more than those of the M group. The median BPDAI at week 4 was 0 (range: 0.0–3.0) in the D + M group and 10.0 (5.0–12.0) in the M group (P < 0.001). Patients treated with dupilumab experienced a faster cessation of new blisters, quicker glucocorticoid reduction, shorter healing times, and shorter hospital stays (P < 0.001). Additionally, after two weeks of treatment, the levels of eosinophils and immunoglobulin E also decreased (P < 0.001). Follow-up studies further demonstrated that dupilumab monotherapy was associated with a lower recurrence rate. Notably, no serious adverse effects were observed in the study. ConclusionsOur study provides evidence for the efficacy of dupilumab in the treatment of BP based on prospective studies. Additionally, our findings suggest that dupilumab can be considered a reliable single-agent maintenance treatment due to its good safety profile and lower relapse.

Matching-Adjusted Indirect Comparison of the Long-Term Efficacy Maintenance and Adverse Event Rates of Lebrikizumab versus Dupilumab in Moderate-to-Severe Atopic Dermatitis.

Lebrikizumab and dupilumab are monoclonal antibodies approved for treating moderate-to-severe atopic dermatitis (AD). Both have demonstrated efficacy and safety over the 16-week SOLOs and ADvocate trials. However, AD is a chronic and relapsing inflammatory disease, and the long-term maintenance of efficacy is critical for achieving disease control from the perspective of patients, physicians, and regulatory agencies. This study aims to compare the long-term efficacy and safety of lebrikizumab every 4weeks (Q4W) and dupilumab every week or every 2weeks (QW/Q2W) among adult patients who have achieved treatment efficacy following the induction period of 16weeks. Lebrikizumab's efficacy was assessed using individual patient data (IPD) from the ADvocate 1 and 2 monotherapy trials. Dupilumab's efficacy was evaluated using aggregate data from the adult-exclusive SOLO-CONTINUE trial. Due to the absence of a common comparator trial arm, we employed an unanchored matching-adjusted indirect comparison (MAIC), a robust methodology widely accepted by health technology assessment (HTA) agencies. This re-weights ADvocate IPD to align with SOLO-CONTINUE's prognostic factors and effect modifiers. We compared lebrikizumab's adjusted outcomes with dupilumab outcomes at week52, focusing on 75% improvement in the Eczema Area and Severity Index from baseline (EASI-75), Investigator's Global Assessment (IGA) score of 0 or 1, and overall adverse event (AE) rates. Sensitivity analyses were conducted to test various combinations of matching variables. Adults on lebrikizumab Q4W were more likely to maintain IGA 0/1 through the 36-week maintenance period (weeks16-52) compared with those on dupilumab QW/Q2W [risk ratio (RR) 1.334; 95% confidence interval (CI) 1.02-1.74; p = 0.035]. Both treatments demonstrated comparable efficacy in terms of EASI-75 maintenance (RR 0.937; 95% CI 0.78-1.13; p = 0.490) and similar AE rates (RR 1.052; 95% CI 0.90-1.23; p = 0.526). Sensitivity analyses substantiated these findings. Our findings suggest that lebrikizumab Q4W may provide equal or superior long-term maintenance of efficacy measured with EASI-75 and IGA 0/1 compared with dupilumab QW/Q2W, with the advantage of requiring less frequent doses.

Dupilumab and subcutaneous immunotherapy for the treatment of refractory moderate to severe atopic dermatitis: A preliminary report

Subcutaneous immunotherapy (SCIT) and dupilumab are important treatments for patients with moderate to severe atopic dermatitis (AD). However, in clinical practice, poor response to allergen immunotherapy (AIT) or dupilumab has been observed in some patients. It is unknown whether combining dupilumab and SCIT can improve treatment responses in patients with moderate to severe AD that is resistant to dupilumab or SCIT monotherapy. This single-centre, retrospective, observational, real-world study evaluated the efficacy and safety of dupilumab and SCIT for refractory moderate to severe AD. The data of ten patients with moderate to severe atopic dermatitis who were treated with dupilumab and SCIT were retrospectively analysed. The scoring atopic dermatitis (SCORAD) score, numerical rating scale (NRS), and atopic dermatitis control test (ADCT) scores and eosinophil and total IgE levels before and after add-on therapy were compared and analysed. The SCORAD, NRS, and ADCT scores decreased significantly at four and 12 weeks after the initiation of add-on therapy and plateaued during maintenance treatment. The eosinophil and total IgE levels were not significantly different before and after add-on therapy. No serious adverse reactions were reported in any patient during add-on therapy. This study indicates that the combination of dupilumab and SCIT safely improves the treatment response of patients with moderate to severe AD who are resistant to dupilumab or SCIT monotherapy.

Long-Term Efficacy of Dupilumab for the Treatment of Prurigo Nodularis: A Case Series

Prurigo nodularis is a chronic, pruritic dermatologic condition that results in nodule formation on the skin that is often treatment refractory and can impair quality of life. The underlying biological mechanism of prurigo nodularis formation is not completely understood, however, many affected patients have an underlying atopic diathesis. Existing therapies provide inadequate outcomes. Dupilumab has recently been approved for the treatment of prurigo nodularis, however, long term efficacy beyond one year has yet to be established. Here we present a series of four patients with prurigo nodularis that were successfully treated with dupilumab and maintained efficacy with a range of 26 months to 79 months.

Biologic drugs and allergen immunotherapy: potential allies

Allergen-specific immunotherapy (AIT) is a proven efficacy treatment for allergic rhinitis (AR), asthma, and Hymenoptera venom allergy, but its use in food allergy (FA) is still under investigation. Because some efficacy and safety concerns still remain, biologic drugs, including omalizumab and dupilumab, have been studied as an adjunctive therapy to AIT for these conditions. In this article, the evidence supporting the use of monoclonal antibodies (mAbs) as an add-on therapy to AIT for FA, AR, asthma, and Hymenoptera venom allergy has been reviewed. The review will delve into the mechanisms of action of different mAbs, their efficacy, and how they can be integrated into personalized medicine approaches to treat allergic diseases. Furthermore, future research areas will be considered. Evidence suggests that omalizumab in combination with AIT may be a beneficial option for respiratory allergies or food desensitisation, especially during the escalation or build-up phase, when adverse events are more frequent. Currently, there is a small number of well-structured clinical trials in Hymenoptera venom allergy, and the available data consist mainly of single-case reports that provide information of limited value. Dupilumab has been studied as adjunctive therapy in patients with respiratory and FAs. Clinical trials are ongoing to evaluate the efficacy of dupilumab as monotherapy or as an adjunct to oral immunotherapy (OIT) in peanut allergy. Other studies are investigating the use of dupilumab in patients with multiple FAs and as an adjunct to milk OIT. Overall, mAbs have the potential to improve outcomes in various allergic conditions when used as an add-on to AIT, especially during the build-up phase. Further research is needed to fully understand their optimal dosing and duration of treatment, as well as to identify which patients may benefit the most from these therapies.

Dupilumab Efficacy in Patients with Type 2 Asthma with and without Elevated Blood Neutrophils.

Elevated neutrophil counts in blood, sputum, or lung have been associated with poor clinical outcomes and more severe disease in patients with type 2 asthma. In the phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200 and 300 mg every 2 weeks compared with matched placebo significantly reduced severe asthma exacerbations and improved forced expiratory volume in 1 s (FEV1) in patients with uncontrolled, moderate-to-severe asthma. This post hoc analysis explored the efficacy of dupilumab in patients with type 2 asthma enrolled in QUEST with or without elevated blood neutrophil counts. Annualized severe exacerbation rates during the 52-week treatment period and least-squares mean change from baseline in FEV1 over time were evaluated for patients with elevated type 2 biomarkers at baseline (blood eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 20 ppb; and eosinophils ≥ 300 cells/µL or FeNO ≥ 50 ppb) and low (<4,000 cells/µL) or high (≥4,000 cells/µL) neutrophil counts. Dupilumab significantly reduced annualized severe exacerbation rates compared with placebo during the 52-week treatment period in patients with elevated type 2 biomarkers, irrespective of baseline neutrophil count (P < 0.0001 for all comparisons). Significant improvements in FEV1 versus placebo were observed as early as Week 2 and over the 52-week treatment period, irrespective of baseline neutrophil count (P < 0.001 for all comparisons). Safety findings were similar across all subgroups, regardless of neutrophil counts at baseline. Dupilumab treatment significantly reduced annualized severe exacerbation rates and improved lung function in patients with uncontrolled, moderate-to-severe, type 2 asthma, irrespective of baseline blood neutrophil count. This trial is registered with NCT02414854.

Efficacy and Safety of Dupilumab for the Treatment of Severe Atopic Dermatitis in Clinical Practice: A Single Center Experience

BackgroundDupilumab is a new targeted therapy for severe atopic dermatitis (AD) with limited real-world evidence. ObjectiveExplore our experience with dupilumab for AD in clinical practice at a tertiary care center. Material and methodUnicentric observational retrospective study including adult and pediatric patients with severe AD receiving dupilumab between December 2017 and December 2021. The Eczema Area and Severity Index (EASI) score, Pruritus Numerical Rating Scale (P-NRS) and Sleep disturbance Numerical Rating Scale (S-NRS) were recovered to assess severity and response. ResultsFifty-nine patients received dupilumab: 52, 48, 26 and 13 patients reached 6, 12, 24 and 36 months of treatment, respectively. The EASI-75 response rates were 94.2%, 95.8%, 92.3% and 100% at months 6, 12, 24 and 36. The EASI-90 response rates were 63.5%, 72.9%, 84.6% and 92.3% at months 6, 12, 24 and 36. The EASI <7 response rates were 92.3%, 91.7%, 88.5% and 100% at months 6, 12, 24 and 36. The P-NRS ≥4 reduction rates were 86%, 87.5%, 92.3% and 100% at months 6, 12, 24 and 36. The S-NRS ≥4 reduction rates were 82.7%, 85.4%, 100% and 100% at months 6, 12, 24 and 36. Adverse events were mild and occurred in 20.3% of patients, all of them adults. ConclusionOur findings support dupilumab's favorable efficacy and tolerability profile in clinical practice. Dupilumab offers a rapid and sustained response, regardless of combined therapy. Longer follow-ups are still required to adequately assess its performance.

Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis

To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.

S461 Dupilumab Efficacy in Eosinophilic Esophagitis Persists for Histologic, Symptomatic, and Endoscopic Outcomes Regardless of Concomitant High-Dose Proton Pump Inhibitor Use

S461 Dupilumab Efficacy in Eosinophilic Esophagitis Persists for Histologic, Symptomatic, and Endoscopic Outcomes Regardless of Concomitant High-Dose Proton Pump Inhibitor Use

Efficacy of dupilumab in real practice in the treatment of severe forms of asthma and atopic dermatitis (comparative retrospective study)

Dupilumab, a fully human monoclonal antibody directed against the common α-subunit of interleukin (IL)-4 receptors and blocking signaling from both IL-4 and IL-13, may be recommended for the treatment of moderate to severe atopic dermatitis (AD) and bronchial asthma (BA). To perform a comparative assessment of the effectiveness of maintenance therapy with dupilumab in patients with severe BA as the main indication for genetically engineered biological drugs and in patients with severe asthma with concomitant severe AD as the indication for targeted therapy. A 6-month retrospective comparative study was performed at the specialized reference center for allergology and immunology. The study included 115 adult patients of both sexes treated with dupilumab for uncontrolled severe asthma as the main indication for targeted therapy (BA group; n=65) or for a combination of severe uncontrolled asthma and severe AD (BAAD; n=50). Dupilumab was administered subcutaneously for 6 months. The first dose was 600 mg once and then 300 mg Q2W. Evaluation of the effectiveness of dupilumab therapy at 6 months of treatment in both groups included achieving asthma control (ACT, ACQ5), improving pulmonary function test, reducing the risk of exacerbations and the need for systemic glucocorticosteroids (SGCS), improving quality of life (AQLQ), change of biomarkers (FeNO, eosinophil count) and the course of comorbid diseases, including improvement in the AD (SCORAD, EASI) and rhinosinusitis polyposa (SNOT-22). During dupilumab therapy, in a significant proportion of patients, regardless of the presence or absence of other T2-associated diseases (e.g., AD or rhinosinusitis polyposa), an improvement in asthma was demonstrated as early as in the first 6 months of treatment with dupilumab in all recommended domains for assessing the response to targeted therapy: improving asthma control and respiratory function, reducing the frequency of moderate and severe exacerbations associated with the use of SGCS and/or hospitalization, a positive effect on the quality of life and the comorbid diseases, as well as a cumulative reduction in the need for SGCS.

Efficacy of dupilumab in patients with uncontrolled, moderate-to-severe asthma with fungal sensitization.

Fungal sensitization (FS) exacerbates asthma in patients who have elevated type 2 inflammatory response. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation in multiple diseases. This post hoc analysis, funded by the manufacturers of dupilumab, was conducted to assess dupilumab efficacy in patients from the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) and TRAVERSE open-label extension (NCT02134028) study who had uncontrolled, moderate-to-severe asthma with type 2 inflammatory phenotype (defined as blood eosinophil count ≥150 cells/μL or FeNO ≥25 ppb) and with FS (defined as IgE specific to Alternaria alternata, Aspergillus fumigatus or Cladosporium herbarum >0.35 IU/mL). We evaluated annualized rate of severe exacerbations (AER), change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV1 ), asthma control (per 5-item Asthma Control Questionnaire [ACQ-5]) and biomarker levels (blood eosinophil count, fractional exhaled nitric oxide [FeNO], total IgE, fungal-specific IgEs, thymus and activation-regulated chemokine [TARC] and eotaxin-3). Dupilumab vs. placebo reduced AER, improved pre-BD FEV1 and asthma control (ACQ-5), and reduced serum IgE levels, blood eosinophil count, TARC, eotaxin-3 and FeNO in patients both with and without FS after 52 weeks of treatment in QUEST. Reductions in asthma exacerbation rates and improvements in all other variables were sustained over the TRAVERSE open-label extension study. Dupilumab demonstrated efficacy during prolonged treatment in patients with uncontrolled, moderate-to-severe asthma with FS.

Long-Term Efficacy of Dupilumab for Eosinophilic Chronic Rhinosinusitis.

Eosinophilic chronic rhinosinusitis (eCRS) is a type 2 inflammatory disease that frequently recurs after surgery. In recent years, dupilumab has been available for the treatment of refractory chronic rhinosinusitis since 2020 in Japan. Although there are some reports of its usefulness, there are not enough reports of its clinical efficacy for longer than 1 year, especially for olfactory recovery. Twenty patients with eCRS who had recurrence after surgery and had been receiving dupilumab were enrolled retrospectively. The nasal polyp score (NPS), computed tomography (CT) score, T&T olfactometer, and olfactory cleft opacification on CT were evaluated at baseline, at an average of 5.1 months later (short term), and at an average of 18.3 months later (long term). At the short-term evaluation, there were significant improvements in the NPS and CT scores (P < .001, P = .008, respectively). The CT score was further improved at the long-term evaluation compared to the short-term evaluation (P = .018) and baseline (P = .008). T&T detection/recognition thresholds and olfactory cleft opacification showed significant improvements only at the long-term evaluation compared to baseline (P = .002, P = .006, and, P = .006, respectively). The NPS remained improved, and the CT score showed further improvement with long-term treatment, whereas olfactory function and olfactory cleft opacification showed significant improvement only after long-term treatment. There was a dissociation between the time to improve in the NPS and CT scores and the time to improve in olfactory function and olfactory cleft opacification. Based on these results, dupilumab should be administered for longer than 1 year, especially for olfactory function.

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose.

Dupilumab has been shown to improve clinical outcomes long term while reducing oral corticosteroid (OCS) dose in patients with severe OCS-dependent asthma. This post hoc analysis assesses the impact of OCS dose at baseline (≤10 or >10 mg·day-1) on long-term outcomes of dupilumab treatment. Annualised severe asthma exacerbation rates, forced expiratory volume in 1 s (FEV1), measures of asthma control and quality of life, and OCS dose were evaluated in patients from the phase 3 VENTURE trial with severe OCS-dependent asthma, further categorised by OCS dose ≤10 or >10 mg·day-1 at parent study baseline (PSBL), who enrolled in TRAVERSE. Dupilumab reduced the annualised exacerbation rate in VENTURE, and it remained low throughout TRAVERSE (0.202-0.265 (OCS ≤10 mg·day-1 at PSBL) and 0.221-0.366 (OCS >10 mg·day-1 at PSBL)). Improvements in pre-bronchodilator FEV1, asthma control and quality of life observed in VENTURE dupilumab patients were sustained throughout TRAVERSE. Patients on placebo during VENTURE showed rapid improvements in FEV1 upon initiating dupilumab in TRAVERSE, which were sustained to the end of TRAVERSE. Reductions in OCS dose observed in VENTURE were maintained throughout TRAVERSE, with more than two-thirds of patients achieving reductions in OCS doses to ≤5 mg·day-1 by TRAVERSE week 48. Improvements in clinical outcomes and reductions in OCS dose with dupilumab observed in VENTURE were maintained throughout TRAVERSE, regardless of baseline disease severity. Patients who switched from placebo in VENTURE to dupilumab in TRAVERSE had improved clinical outcomes and reductions in OCS dose comparable to those given dupilumab in VENTURE.

Targeting IL-4 and IL-13 Receptors on Eosinophils in CRSwNP Patients: The Clinical Efficacy of Dupilumab.

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease linked to type 2 inflammation. Several biologics have demonstrated therapeutic potential for the treatment of this pathology in which IL-4, IL-5 and IL-13 represent the major cytokines involved in the control of eosinophilic respiratory inflammation. 25% of CRSwNP patients relapse after the use of oral glucocorticoids or after surgery and often require several surgeries during their lifetime. In our study we enrolled 14 patients, 11 male and 3 female. The inclusion criteria were: age ≥ 18 years; confirmed diagnosis of chronic rhinosinusitis with severe nasal polyposis; disease severity with NPS Nasal Polyposis Endoscopic Score total score ≥ 5 and/or SNOT-22 ≥ 50; previous treatment failure due to lack of efficacy or discontinuation of systemic corticosteroid therapy and/or non-response or recurrence following surgery. The results presented in this study showed the ability of Dupilumab to improve all the parameters analysed. In particular, statistically significant data were obtained for NPS, SNOT-22, NRS, and IgE in patients exposed to Dupilumab treatment for 24 weeks, highlighting the ability of Dupilumab to produce clinical benefit in CRWwNP patients. In light of these data, the administration of dupilumab every two weeks represents a valid clinical strategy that ENT specialists can adopt for the treatment of adults with inadequately controlled CRSwNP.

Effectiveness of Dupilumab for Chronic Prurigo in Chinese Patients: A Real-World Case Series Study.

Treatment of chronic prurigo (CPG) is challenging. As an antagonist of IL-4R, dupilumab has shown effectiveness in treating CPG in several clinical studies. Recently, the US Food and Drug Administration (FDA) approved dupilumab for the treatment of prurigo nodularis (PN). The purpose of this study was to examine the efficacy of dupilumab in Chinese patients with CPG, and to analyze the difference in response between subtypes of CPG. This retrospective study included 18 patients with CPG who were treated with dupilumab for at least 16 weeks from March 2022 to October 2022. Disease severity and patient self-assessment questionnaires were assessed at baseline and each visit, including the peak Pruritus Visual Analogue Scale (PP-VAS), Prurigo Activity and Severity Score (PAS), Investigator Global Assessment (IGA), Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS) and Itchy-specific Quality of Life questionnaire (ItchyQoL). After 2 weeks of dupilumab treatment, pruritus scores were significantly reduced as measured by PP-VAS scores. Prurigo Activity and Severity scores decreased significantly at Week 2, whereas IGA improved significantly at Week 8. The DLQI, HADS, and ItchyQoL scores at Week 16 also showed significant improvement from baseline. Patients in all subtypes showed improvement in pruritus and lesion severity. Dupilumab was effective in improving pruritus and lesions in patients with various subtypes of CPG.

A clinical observational study on the preliminary effect of dupilumab in the treatment of severe asthma

Objective: To investigate the effect and safety of dupilumab in the treatment of patients with severe asthma in a preliminary clinical observational study. Methods: This study retrospectively analyzed the clinical data of 20 patients with severe asthma who received dupilumab for 4-12 months between 2019 and 2022 at the First Hospital of Guangzhou Medical University, comparing pre-and post-treatment laboratory data, oral glucocorticoid dose (OCS), asthma control test (ACT) and adverse effects. The median age of the 20 patients was 48.5 (41.0-52.8) years, including 14 males and 6 females. The clinical data of 10 patients treated with other biologic agents were further analyzed to determine the reasons for switching to biologic drug treatment and the efficacy of dupilumab in these patients. Paired t-tests or Wilcoxon signed-rank tests were used for comparisons. Mann-Whitney analysis was used for inter-group comparison, and chi-square test or Fisher test was used for inter-group comparisons of count data. Results: A total of 20 patients were included in this study. All 20 severe asthma phenotypes were type 2 (T2)-high and completed at least the first 4 months of treatment, including 17 patients who completed 12 months of treatment. Among patients who completed 4 months of treatment, the asthma exacerbation score decreased from 1.0(0.3-1.0) episodes/4 months to 0.0(0.0-1.0) episodes/4 months, P<0.001, and FEV1/FVC increased from 58.4% (50.5%-69.0%) to 66.9% (59.6%-77.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 15 (75%) to 9 (45%), P<0.05. Among patients who completed 12 months of treatment, the asthma exacerbation score decreased from 1.0(0.5-1.0) episodes/4 months to 0.0 (0.0-0.0) episodes/4 months, P<0.01, and FEV1/FVC increased from 57.9% (49.6%-67.8%) to 72.7% (64.6%-78.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 13 (76%) to 6 (35%), P<0.01. In 10 patients with a history of previous biologic therapy, the most common reasons for switching to a biologic were a poor response to previous monoclonal antibodies (40%) and loss of control of asthma symptom control after discontinuation of monoclonal antibodies (30%). The remaining reasons were patients' uncontrolled symptoms of chronic rhinosinusitis (20%) and irregular or underdosed use of previous biologics (10%). After 4 months of switching to dupilumab, 10 patients experienced varying degrees of improvement in asthma control. Conclusions: The application of dupilumab for the treatment of T2-high severe asthma showed good efficacy and few adverse effects. Biologically targeted therapy is an important treatment approach to achieving better control of severe asthma.

Asthma improvement in patients treated with dupilumab for severe atopic dermatitis.

Atopic dermatitis (AD) is considered a systemic type 2 immune driven disease, and it is associated to many atopic comorbidities including asthma. The aim of our study was to prospectively evaluate the respiratory outcomes in patients with persistent allergic asthma treated with dupilumab due to severe AD (sAD). We enrolled eligible patients with sAD for dupilumab treatment from September 2018 to December 2020. We then selected the subgroup of patients sensitized to perennial allergens. Dupilumab's efficacy and safety on AD and comorbid asthma were assessed at baseline, one month, four months, and then every 4 months up to one year. A total of 437 patients with sAD were enrolled for dupilumab treatment due to sAD, and 273 reached 48 weeks of therapy. Respiratory outcomes were evaluated in the 85 asthmatic patients with positivity only to perennial allergens. Our patients showed statistically and clinically significant improvement in asthma control (Asthma Control Test and Asthma Control Questionnaire) and airway obstruction parameters (FEV1), in addition to the expected AD-related skin outcomes. Specifically, a significant improvement was achieved at the fourth month of dupilumab therapy, and this trend was maintained up to twelve months, regardless of asthma severity. Our results showed the overall improvement of the clinical picture that dupilumab offers for patients with severe AD and persistent allergic asthma of any severity, highlighting the importance of a global multidisciplinary approach of type 2 driven disease.

Real-World Efficacy of Dupilumab in Severe, Treatment-Refractory, and Fibrostenotic Patients With Eosinophilic Esophagitis

Dupilumab is approved for treatment of eosinophilic esophagitis (EoE), but real-world data are lacking. We aimed to determine the real-world efficacy of dupilumab in patients with severe, treatment-refractory, and fibrostenotic EoE. We conducted a retrospective cohort study of EoE patients prescribed dupilumab and who were treatment-refractory to standard modalities. Patient demographics, clinical characteristics, EoE history, and procedural data (including the histologically worst, predupilumab, and postdupilumab endoscopies) were extracted from medical records. Symptomatic, endoscopic, and histologic responses were assessed for the worst and predupilumab endoscopies compared with the postdupilumab endoscopy. We identified 46 patients with refractory fibrostenotic EoE who were treated with dupilumab. Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the predupilumab esophagogastroduodenoscopies. The peak eosinophil counts decreased markedly, and postdupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field and 6 or fewer eosinophils per high-power field, respectively, and the Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all). Although the proportion of strictures was stable, there was a significant increase in the predilation esophageal diameter (from 13.9 to 16.0 mm; P < .001). Global symptom improvement was reported in 91% (P < .001). In this population of severe, refractory, and fibrostenotic EoE patients, most achieved histologic, endoscopic, and symptom improvement with a median of 6 months of dupilumab, and esophageal stricture diameter improved. Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials.

Dupilumab efficacy in high sleep disturbance management among patients with type 2 asthma

BackgroundPatients with asthma often experience sleep disturbances. We assessed the 5-item Asthma Control Questionnaire (ACQ-5) score ≥2.5 as a useful threshold to identify patients with moderate-to-severe type 2 asthma and high sleep disturbance (HSD) and investigated dupilumab efficacy on clinical and sleep-related outcomes among patients with HSD. MethodsQUEST (NCT02414854) data were used in this post hoc analysis. A composite endpoint from validated patient-reported outcomes was developed to identify patients with HSD using sleep-related items from the ACQ-5, Asthma-Related Quality-of-Life Questionnaire, Rhino-Conjunctivitis Quality-of-Life Questionnaire, and Sino-Nasal Outcome Test-22. Impairment in at least 1 item was considered an indication of HSD. Change from baseline to Week 52 in nighttime symptoms, ACQ-5 score, lung function, annualized severe exacerbation rates (AER), and short-acting β-agonists use during treatment was used to assess dupilumab efficacy. ResultsIn type 2 asthma patients, 64% had HSD at baseline; of those with ACQ-5 ≥2.5 at baseline, 82% had HSD. In this population, dupilumab reduced nighttime symptoms and ACQ-5 score by 0.31 and 0.56 points, respectively, by Week 52 versus placebo, and led to a 66% reduction in AER during QUEST and 0.34 L improvement in pre-bronchodilator (pre-BD) forced expiratory volume in 1 s (FEV1) at Week 52. ConclusionA majority of patients with moderate-to-severe type 2 asthma with ACQ-5 ≥2.5 at baseline had HSD. Dupilumab reduced nighttime symptoms and exacerbations, and improved lung function, overall asthma control, and quality of life. Further studies are needed to confirm the association between ACQ-5 score ≥2.5 and higher sleep disturbance rates.