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Purpose: Since its release, Dupilumab has shown great results in treating severe uncontrolled CRSwNP. However, there is a lack of real-world data beyond 12 months of follow-up, and it is not clear to what extent biomarkers are appropriate for monitoring and predicting the Dupilumab therapy success. Hence, this study aims to analyze biomarkers for monitoring therapy, predicting therapy success and assess the effect of Dupilumab in real-world settings. Methods: The follow-up was performed with 104 patients retrospectively up to 22 months, assessing SNOT-22, NPS, olfactometry, ACS, FEV-1, and blood biomarkers (total serum IgE, Eosinophils, ECP). Patients were divided into subgroups depending on their pretherapeutic biomarker levels and subsequent development was analyzed. Results: There was substantially improvement in all clinical parameters up to 1 year and then continuously up to month 22. Patients with initially elevated baseline blood eosinophil counts (> 0.5 billion/L) had a trend of better SNOT-22 development after 1 year (− 12.19 points, p = 0.03). The course of total serum IgE showed moderate correlation with almost all clinical variables obtained. Therapy was well tolerated with only mild and transient adverse events. Conclusion: Dupilumab has considerably reduced symptoms and disease severity even beyond 1 year of treatment, supporting its role as targeted and effective treatment option for CRSwNP. Our data shows that total serum IgE is a promising biomarker for the monitoring during the treatment with Dupilumab. Elevated pre-therapeutic serum eosinophil counts may be a predictor of good subjective response to therapy. Larger cohorts and a long-term-follow-up over years are needed to further consolidate these findings. [ABSTRACT FROM AUTHOR]

Background: Dupilumab, a monoclonal antibody targeting IL-4 and IL-13, has demonstrated its efficacy in several clinical trials. However, to date, real-life data remains limited. Objective: The aim of our study was to assess the real-life impact of dupilumab on patients with severe and uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) quality of life. Materials and methods: This was a retrospective, monocentric, observational, real-life study, conducted in accordance with the STROBE guidelines. The following parameters were collected before treatment and at 1, 4, and 12 months: Sino-Nasal Outcome Test-22 (SNOT-22), nasal polyp score (NPS), Sniffin' Sticks-16 (SST-16), visual analog scale (VAS) for loss of smell, nasal congestion score (NCS), gustatory VAS, asthma control, oral corticosteroid usage, surgery rates, and occurrence of side effects. Results: The study included 47 patients. SNOT-22 scores decreased from 52.4 ± 24.3 to 12.7 ± 10.5 at 12 months (p < 0.001). NPS decreased from 6.15 ± 1.71 to 1.57 ± 1.40 at 12 months (p < 0.001). SST-16 scores increased from 1.6 ± 2.83 to 9.1 ± 5.4 at 12 months (p < 0.001). NCS decreased from 2.45 ± 0.72 to 0.38 ± 0.63 at 12 months (p < 0.001). Prior to treatment, 72.3% were using oral corticosteroids, compared to 17.0% at 12 months (p < 0.01). Two patients required additional surgery, and 17% reported completely uncontrolled asthma, compared to 0% at 12 months (p < 0.01). Conclusion: Our real-life results confirm the efficacy of Dupilumab in the treatment of severe and uncontrolled CRSwNP. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions, significantly impacting physical health and quality of life. The pathogenesis of AD involves genetic predisposition, immune dysregulation, and environmental factors, with a defective skin barrier playing a crucial role. Treatment options for AD include both topical and systemic therapies, with advanced treatments like Janus kinase inhibitors and biologics offering significant improvements but facing limitations in safety and dosing frequency. Extended half-life antibodies represent a promising advancement for the management of immune-mediated inflammatory diseases, including AD. These antibodies, engineered for prolonged circulation and reduced dosing frequency, target key cytokines and immune pathways known to be involved in the pathogenesis of AD, offering potential for less frequent administration while maintaining efficacy. Currently, two such agents are in phase 2 trials. APG777, targeting interleukin-13 (IL-13), and IMG-007, targeting OX40 receptor, have shown promising preclinical and early clinical results. They demonstrated prolonged half-lives and the potential for less frequent dosage regimen, along with significant improvements in AD symptoms. These therapies could enhance patient adherence and reduce healthcare burdens by decreasing injection frequencies and clinic visits. As research continues, extended half-life antibodies could significantly improve AD management and patient quality of life. Further studies will determine the long-term safety and efficacy of extended half-life antibodies, with ongoing innovations in antibody engineering likely to broaden their applications and benefits. [ABSTRACT FROM AUTHOR]

Introduction: Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 assessed efficacy of upadacitinib 30 mg and upadacitinib 15 mg against placebo, while Heads Up assessed efficacy of upadacitinib 30 mg in a head-to-head trial against dupilumab 300 mg. A head-to-head trial of upadacitinib 15 mg against dupilumab 300 mg has not been conducted. Network meta-analysis has shown that upadacitinib 30 mg and upadacitinib 15 mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated more stringent outcomes. Methods: A population-adjusted indirect comparison was conducted using post hoc individual patient data from Measure Up 1 and 2 and Heads Up to estimate how upadacitinib 15 mg would have performed if included in Heads Up by adjusting for patient-level covariates. Absolute response rates at weeks 4, 16, and 24 were estimated for the following outcomes: no/minimal itch [Worst Pruritus Numerical Rating Scale (WP-NRS) score of 0/1], Eczema Area and Severity Index (EASI) score of ≤ 3 (EASI ≤ 3), 100% improvement in EASI (EASI 100), both ≥ 90% improvement in EASI (EASI 90) and WP-NRS 0/1, both EASI ≤ 3 and WP-NRS 0/1, and both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to treat population for the clinical trials, and used non-responder imputation. Results: Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30 mg, followed by upadacitinib 15 mg and then dupilumab. This pattern was observed at week 4, week 16, and week 24. Conclusions: For adults with moderate-to-severe AD, upadacitinib 30 mg appears to be the most efficacious treatment in attaining more stringent and composite outcomes across multiple timepoints, followed by upadacitinib 15 mg and then dupilumab 300 mg. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD), with its hallmark symptoms of pruritus and skin lesions, often impairs patients' quality of life. We assessed time spent with clear/almost clear skin and no/minimal itch during upadacitinib treatment versus placebo or dupilumab among patients with moderate-to-severe AD. Methods: This analysis consisted of a post hoc analysis of Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 were replicate, randomized, double-blind, placebo-controlled phase 3 studies with patients randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 16 weeks. Heads Up was a head-to-head, randomized, double-blind, double-dummy, phase 3b study with patients randomized (1:1) to upadacitinib 30 mg or subcutaneous dupilumab 300 mg for 24 weeks. Skin clearance was assessed with the Eczema Area and Severity Index (EASI) at baseline, weeks 1, 2, and 4, and every 4 weeks thereafter. Itch was assessed using the Worst Pruritus Numerical Rating Scale (WP-NRS) daily over 16 weeks and every 2 weeks thereafter to week 24 in Heads Up. Results: This analysis included 1683 patients in Measure Up 1 and 2 and 673 patients in Heads Up. Through 16 weeks in Measure Up 1 and 2, patients receiving upadacitinib spent 9.8–13.4 times as many days with an EASI 90 response and 7.0–10.3 times as many days with a WP-NRS 0/1 response versus placebo. In Heads Up, patients receiving upadacitinib spent 2.0 and 1.7 times as many days through 16 and 24 weeks, respectively, with an EASI 90 response versus dupilumab. Through 16 and 24 weeks, patients receiving upadacitinib spent 3.0 and 2.6 times as many days, respectively, with a WP-NRS 0/1 response versus dupilumab. Conclusions: Patients with moderate-to-severe AD spent more time with clear/almost clear skin and no/minimal itch with upadacitinib versus placebo or dupilumab. Trial Registration: ClinicalTrials.gov identifier, Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), Heads Up (NCT03738397). [ABSTRACT FROM AUTHOR]

Introduction: In chronic spontaneous urticaria (CSU), interleukin (IL)-4 and IL-13 may promote mast cell activation directly via IL-4 receptor expression, or indirectly via upregulated immunoglobulin E (IgE) production. Dupilumab significantly improved CSU signs and symptoms in the phase 3, randomized, placebo-controlled LIBERTY-CSU CUPID Study A. This analysis explores the impact of dupilumab on CSU signs and symptoms and serum IgE levels in patients from LIBERTY-CSU CUPID Study A with serum total IgE above and below 100 IU/mL at baseline. Methods: Patients with H1-antihistamine-refractory CSU received dupilumab (n = 70) or placebo (n = 68) for 24 weeks. Efficacy endpoints were change from baseline to weeks 12 and 24 in serum total IgE levels, Itch Severity Score over 7 days (ISS7), Urticaria Activity Score over 7 days (UAS7), and Hives Severity Score over 7 days (HSS7) in dupilumab- or placebo-treated patients with serum total IgE above and below 100 IU/mL at baseline. Results: Dupilumab treatment significantly reduced median (interquartile range) IgE levels at week 12 [dupilumab: −31.9% (−41.9; −22.6); placebo: −6.3% (−21.3; 14.9)] and week 24 [dupilumab: −48.2% (−56.8; − 39.5); placebo: − 6.3% (−34.5; 14.8)]. Similar IgE reductions relative to baseline were observed in dupilumab-treated patients regardless of baseline IgE level. Dupilumab treatment improved ISS7, UAS7, and HSS7 over 12 and 24 weeks, regardless of baseline serum IgE level (interaction p ≥ 0.59 for all treatment by subgroup comparisons), with weak correlations (r < 0.2) observed between IgE level changes and ISS7, UAS7, and HSS7 outcomes. Conclusions: Dupilumab significantly improved CSU signs and symptoms and reduced serum IgE, regardless of baseline IgE levels. In the current analysis, baseline total IgE had no predictive value as a dupilumab treatment response biomarker in CSU. Downregulation of IgE, a key mediator of mast cell activation and histamine release, may at least partially explain the effectiveness of dupilumab in reducing CSU signs and symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04180488. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to assess the effectiveness of fractional exhaled nitric oxide (FeNO) combined with pulmonary function testing (PFT) for predicting the treatment outcome of patients with severe asthma receiving dupilumab. Methods: A total of 31 patients with severe asthma visiting our hospital from January 2022 to June 2023 were included in this study, with 28 patients completing a 16-week course of dupilumab treatment. Baseline clinical data, including demographic information, blood eosinophil counts, serum IgE levels, FeNO, asthma control test (ACT), asthma control questionnaire (ACQ), and other parameters, were collected. A predictive model using a generalized linear model was established. Results: Following the 16-week course of dupilumab treatment, 22 patients showed effective response based on GETE scores, while 6 patients were nonresponders. Notably, significant improvements were observed in clinical parameters such as blood eosinophil counts, serum IgE levels, FeNO, FEV1, FEV1%, ACT, and ACQ in both response groups (p < 0.05). FeNO and pulmonary function tests demonstrated AUC values of 0.530, 0.561, and 0.765, respectively, in predicting the clinical efficacy of dupilumab, which were lower than when FeNO was combined with FEV1%. The combination of FeNO and FEV1% had a sensitivity of 1.000 and specificity of 0.591 in predicting treatment response. Conclusion: The combined assessment of FeNO and FEV1% provides improved accuracy for predicting the clinical efficacy of dupilumab in managing severe asthma. However, further larger scale clinical studies with comprehensive follow-up data are needed to validate the therapeutic efficacy and applicability across diverse patient populations. [ABSTRACT FROM AUTHOR]

Objective: Modification of the immune system with biologics raises theoretical concerns about the risk of infections but it is still unclear whether currently routinely used biologics in severe asthma may facilitate the development of pneumonia. Therefore, we aimed to determine whether omalizumab, mepolizumab, benralizumab, and dupilumab are associated with pneumonia in a real-world setting. Methods: A retrospective disproportionality analysis was performed using adverse event (AE) reports submitted to FAERS from January 2020 to September 30, 2023. MedDRA was used to identify infections and infestations and then pneumonia cases. ROR and PRR were used to measure disproportionality. Results: The percentage of reported cases of pneumonia compared to infections and infestations was highest for mepolizumab (36.8%), followed by omalizumab (32.6%), benralizumab (19.2%) and dupilumab (5.7%). We found a moderate or strong signal for increased risk of pneumonia with mepolizumab (ROR = 3.74, 95%CI 3.50–4.00), omalizumab (ROR = 3.26, 95%CI 3.06–3.49) and benralizumab (ROR = 2.65, 95%CI 2.49–2.83). Conclusions: Mepolizumab, omalizumab and benralizumab, but not dupilumab, were associated with high odds of reporting pneumonia. Our results represent only potential associations between these biologics and pneumonia but not causality. The nature of the FAERS database is such that the cause of the reported events is uncertain. Therefore, we can only roughly estimate the incidence of AEs by the signal strength (ROR value). Nevertheless, although causality could not be assessed, the signal from our study is interesting. We believe it deserves to be further substantiated by real-world studies with robust designs. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) is nonscarring hair loss characterized by Th1 and concomitant Th2 skewing, particularly in atopic patients. Despite novel developments for adult AA, safe and effective treatments for pediatric patients remain limited. Dupilumab, with a well-studied safety profile, may have therapeutic potential for atopic pediatric AA. To evaluate the ability of dupilumab to regrow hair in pediatric AA patients. We conducted a single-center, retrospective, observational study to evaluate hair regrowth [using Severity of Alopecia Tool (SALT)] with dupilumab in 20 children with both AD and AA (age range 5–16 years, mean 10.8 years; baseline SALT range 3–100, mean 54.4). Patient demographics, atopic history, IgE and SALT scores were collected at 12wk follow-up visits, up to > 72wks, to evaluate hair regrowth. Spearman correlations with clinical data were performed. Patients showed clinical improvement over the follow-up period (range 24 to > 72wks, mean 67.6wks) with significant mean(± SD) reduction in SALT at 48wks versus baseline [20.4(± 35.1) vs 54.4(± 37.6), respectively; p < 0.01] and continued improvement up to > 72wks [2.2(± 4.9), p < 0.01]. Baseline SALT positively correlated with disease duration (r = 0.54, p < 0.01), and negatively correlated with improvement in SALT at weeks 24, 36, and 48 (|r|≥ 0.65, p < 0.01 for all comparisons). Baseline IgE positively correlated with improvement in SALT at week 36 (r > 0.60, p < 0.05). Dupilumab was well-tolerated, with no new safety concerns. These real-world data support the utility of dupilumab to safely treat pediatric AA patients, corroborating the role of Th2 skewing in children with AA and associated atopy, warranting larger clinical trials. [ABSTRACT FROM AUTHOR]

Severe uveitis is a rare complication of interleukin-4 receptor alpha blocking by dupilumab in topic dermatitis (AD) patients. The aim of this study was to describe five moderate-to-severe AD patients who developed uveitis during dupilumab treatment and to compare the proteomic profile of aqueous humor (AqH) of dupilumab-associated uveitis (n=3/5 available samples) with non-infectious uveitis (n=27) and cataract controls (n=11). Included patients were treated at the University Medical Center Utrecht (the Netherlands). Active dupilumab-associated uveitis complicated by serous detachment, cystoid macular edema, or secondary glaucoma developed within a median of 6.0 months (interquartile range 2.3–16.5 months) after starting dupilumab. Uveitis resolved after discontinuation of dupilumab and/or treatment with local or systemic corticosteroids. Proteomic profiling of AqH revealed that the molecular profile of dupilumab-associated uveitis resembled that of non-infectious uveitis. In conclusion, dupilumab-associated uveitis is a severe adverse event of dupilumab therapy, requiring urgent referral to an ophthalmologist. [ABSTRACT FROM AUTHOR]

Dupilumab effectively treats atopic dermatitis (AD); however, its role in halting the atopic march remains uncertain. To investigate dupilumab's effect on atopic march in pediatric AD patients versus conventional immunomodulators. This retrospective cohort study utilized data from the TriNetX US Collaborative Network (2011-2024). Pediatric AD patients (≤18 years) were categorized into DUPI-cohort (newly prescribed dupilumab) or CONV-cohort (prescribed conventional immunomodulators without dupilumab). After 1:1 propensity-score matching, we analyzed atopic march progression, defined by the incident asthma or allergic rhinitis (AR). Cumulative incidence was plotted using Kaplan-Meier, with risk assessment via Cox regression. The study included 2192 patients in each cohort. The 3-year cumulative incidence of atopic march progression was lower in the DUPI-cohort than the CONV-cohort (20.09% vs 27.22%; P <.001). The DUPI-cohort demonstrated significant risk reduction in atopic march progression (hazard ratio [HR] 0.68, 95% CI 0.55-0.83), individual asthma (HR 0.60, 0.45-0.81), and individual AR (HR 0.69, 0.54-0.88). Younger patients on dupilumab exhibited a greater risk reduction for atopic march progression and individual asthma, contrasting with the opposite age-related pattern for individual AR. Observational study. Among pediatric AD patients, dupilumab was associated with reduced risk of atopic march progression compared with conventional therapies. [ABSTRACT FROM AUTHOR]

[Display omitted] There is evidence of pathophysiologic diversity in chronic rhinosinusitis with nasal polyps (CRSwNP), but data characterizing the molecular endotypes of CRSwNP and their association with treatment are lacking. This study aimed to identify gene signatures associated with CRSwNP endotypes, clinical features, and dupilumab treatment response. Nasal brushing samples were collected from 89 patients randomized to dupilumab 300 mg every 2 weeks or placebo in the SINUS-52 trial (NCT02898454). Microarrays were used to identify transcriptional clusters and assess the relationship between gene expression and baseline clinical features and clinical response to dupilumab. Endotype signatures were determined using differential expression analysis. Two distinct transcriptional clusters (C1 and C2) were identified, both with elevated type 2 biomarkers. At baseline, C2 patients had higher mean Nasal Polyp Score and higher type 2 biomarker levels than C1 patients. At week 24, significant improvements in clinical outcomes (dupilumab vs placebo) were observed in both clusters, although the magnitude of improvements was significantly greater in C2 than in C1, and more C2 patients demonstrated clinically meaningful responses. Gene set enrichment analysis supported the existence of 2 molecular endotypes: C2 was enriched in genes associated with type 2 inflammation (including periostin, cadherin-26, and type 2 cysteine protease inhibitors), while C1 was enriched in genes associated with T cell activation and IL-12 production. Two distinct gene signatures associated with CRSwNP clinical features were identified; the endotype signatures were associated with clinical outcome measures and magnitude of dupilumab response. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP), an autoimmune bullous dermatosis, occurs predominantly in older individuals. Nemolizumab, a humanized monoclonal antibody against the interleukin (IL)‐31 receptor A, is used to treat severe atopic dermatitis (AD) in Japan. However, it can cause several adverse events, such as exacerbation of AD, erythema, and eosinophilia. Herein, we describe a case of prurigo‐type AD developing BP after nemolizumab administration. A 62‐year‐old man with prurigo‐type AD and asthma presented with serious, refractory itching. After nemolizumab injection, his pruritus was relieved for 2 days. However, on day 3, erythema with blisters and erosions suddenly appeared throughout his body. Pathological examination showed typical BP and the patient's serum anti‐BP180‐NC16a antibody level was 882.5 U/mL. Oral prednisolone (PSL) was initiated and nemolizumab was never used again. Despite high‐dose PSL, new blisters continued to develop, with a rapid elevation of anti‐BP180‐NC16a antibodies to 6930 U/mL. Adding high‐dose cyclosporine and intravenous gamma globulin reduced new blister formation after 9 weeks, and PSL and cyclosporine were gradually tapered. Dupilumab, an anti‐IL‐4 receptor antibody, was initiated after 16 weeks, resulting in continued remission without PSL and cyclosporine. The sudden occurrence of BP in this case suggested that the patient had occult BP before the nemolizumab initiation and that nemolizumab exacerbated BP and made it overt. Blocking the IL‐31 pathway may exacerbate inflammation in AD or BP, resulting in the acceleration of blister formation. This may be countered by blocking the IL‐4/13 pathway with dupilumab. To our knowledge, this is the first case of nemolizumab‐exacerbated BP. [ABSTRACT FROM AUTHOR]

Background: A sub-analysis of the Korean population in the LIBERTY ASTHMA QUEST trial (NCT02414854) revealed that dupilumab effectively treated severe uncontrolled asthma. This study aimed to assess the cost-effectiveness of add-on therapy with dupilumab to background therapy in patients ≥ 12 years of age with uncontrolled severe asthma compared to that of background therapy in South Korea. Methods: The cost-effectiveness analysis was conducted using a Markov model over a lifetime from the Korean healthcare system perspective. Clinical efficacy and utility weights were obtained from post-hoc analyses of the Korean population in the QUEST trial. Data on the costs and treatment setting of exacerbation in a real-world setting were retrospectively collected using the administrative medical database from a single tertiary hospital. Results: The base-case results indicated that add-on dupilumab therapy increases costs ($112,924 for add-on dupilumab versus $29,545 for background therapy alone). However, add-on dupilumab increased quality-adjusted life years (QALYs, 8.03 versus 3.93, respectively), with fewer events of severe exacerbations per patient compared to using the background therapy alone (17.920 versus 19.911, respectively). The incremental cost-effectiveness ratio was $20,325 per QALY. Various sensitivity analyses supported the robustness of the base-case results. Probabilistic sensitivity analysis showed that the probability of add-on dupilumab being cost-effective was 87% at a threshold willingness-to-pay of $26,718 (KRW 35 million) per QALY gained. Conclusions: Dupilumab is cost-effective for adolescents and adults with uncontrolled severe asthma in South Korea. Our study provides evidence to support clinicians and policymakers in making informed decisions for severe asthma management. [ABSTRACT FROM AUTHOR]

Summary The etiology of allergy is closely linked to type 2 inflammatory responses ultimately leading to the production of allergen‐specific immunoglobulin E (IgE), a key driver of many allergic conditions. At a high level, initial allergen exposure disrupts epithelial integrity, triggering local inflammation via alarmins including IL‐25, IL‐33, and TSLP, which activate type 2 innate lymphoid cells as well as other immune cells to secrete type 2 cytokines IL‐4, IL‐5 and IL‐13, promoting Th2 cell development and eosinophil recruitment. Th2 cell dependent B cell activation promotes the production of allergen‐specific IgE, which stably binds to basophils and mast cells. Rapid degranulation of these cells upon allergen re‐exposure leads to allergic symptoms. Recent advances in our understanding of the molecular and cellular mechanisms underlying allergic pathophysiology have significantly shaped the development of therapeutic intervention strategies. In this review, we highlight key therapeutic targets within the allergic cascade with a particular focus on past, current and future treatment approaches using monoclonal antibodies. Specific targeting of alarmins, type 2 cytokines and IgE has shown varying degrees of clinical benefit in different allergic indications including asthma, chronic spontaneous urticaria, atopic dermatitis, chronic rhinosinusitis with nasal polyps, food allergies and eosinophilic esophagitis. While multiple therapeutic antibodies have been approved for clinical use, scientists are still working on ways to improve on current treatment approaches. Here, we provide context to understand therapeutic targeting strategies and their limitations, discussing both knowledge gaps and promising future directions to enhancing clinical efficacy in allergic disease management. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Dupilumab is the first and only biologic agent approved for the treatment of atopic dermatitis (AD) in pediatric patients aged from 6 months to 17 years. The study aimed to evaluate the impact of dupilumab on the occurrence of comorbidities in pediatric patients with AD.In this population‐based cohort study, we utilized electronic health records from multiple healthcare organizations across the United States. Pediatric patients (<18 years of age) with a diagnosis of AD initiating dupilumab were propensity‐score matched 1:1 to those initiating other systemic agents (azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, or systemic corticosteroids). The primary outcomes were new‐onset comorbidities emerging during the study period measured by the risk ratio (RR) and its confidence interval (CI). Subgroup analyses were stratified by age (0–5 years, 6–11 years, and 12–17 years), sex, and race.A total of 3575 pediatric patients with AD treated with dupilumab were matched to 3575 patients treated with other systemic agents. The dupilumab cohort was associated with a lowered risk of new‐onset atopic comorbidities (including asthma [RR, 0.72; 95% CI, 0.59–0.89] and allergic rhinitis [RR, 0.62; 95% CI, 0.52–0.74]), infections (e.g., skin and soft tissue infection [RR, 0.70; 95% CI, 0.63–0.76] and respiratory tract infection [RR = 0.56; 95% CI, 0.51–0.61]), psychiatric disorders (e.g., mood disorder [RR, 0.52; 95% CI, 0.39–0.70] and anxiety [RR, 0.57; 95% CI, 0.46–0.70], sleep disturbance [RR, 0.60; 95% CI, 0.47–0.77]), neurologic and developmental disorders (e.g., attention deficit hyperactivity disorder [RR, 0.54; 95% CI, 0.38–0.75]). Furthermore, the positive effects are found to be more pronounced in younger children (aged 0–5 years) with AD.Treatment with dupilumab compared to systemic agents resulted in reductions in AD‐related comorbidities in pediatric patients. [ABSTRACT FROM AUTHOR]

Linear IgA bullous dermatosis (LABD) is an acquired autoimmune subepidermal blistering disorder. Diagnosis always relies on skin pathology and direct immunofluorescence (DIF), with typical linear deposits of IgA along the basement membrane zone (BMZ). The typical clinical manifestation is tense bullae arranged like the "string of pearls" companied with severe pruritus. Dapsone is often considered first-line therapy for LABD, and it is necessary to test the HLA-B*1301 gene to prevent the occurrence of dapsone-induced hypersensitivity syndrome (DHS). Here we report a case of LABD resistant to corticosteroid and sulfasalazine, while waiting for HLA-B*1301 gene test results, dupilumab was used to control severe pruritus. [ABSTRACT FROM AUTHOR]

Background: Bullous pemphigoid (BP) is an autoimmune disease characterized by the appearance of very pruritic subepidermal blisters. It appears mostly in the elderly and is associated with multiple comorbidities, which makes its management and treatment difficult. The purpose of this systematic review is to compile current information on published cases of BP treated with omalizumab (omalizumab) and dupilumab (dupilumab) in order to obtain information on clinical efficacy and safety data available. Methods: A literature search of all cases of BP treated with omalizumab/dupilumab published in the literature up to January 2024 was performed using the Pubmed database. After an exhaustive search, a total of 61 studies encompassing 886 patients met the inclusion criteria and were included in the review. Results: The majority of patients with BP treated with omalizumab/dupilumab presented a significant improvement in symptomatology, being very safe drugs with minimal side effects. The main limitation of the presented review is the quality of the included studies, most of them being case series or individual cases. The development of studies with a higher level of scientific evidence in the near future would be of great interest. Conclusions: Both omalizumab and dupilumab appear to be effective options for treating BP in patients refractory to other pharmacological therapies. They are drugs with a good safety profile and the adverse reactions associated with their use are infrequent and generally mild. [ABSTRACT FROM AUTHOR]

Background: Indirect comparison among biologics in severe asthma (SA) is a challenging but desirable goal for clinicians in real life. The aim of the study is to define characteristics of a biologic-treated T2-driven-SA population and to evaluate the effectiveness of biologic treatments in a real-world setting by variation in intra/inter-biologic parameters in an up to 4-year follow-up. Methods: Demographic, clinical, functional, and biological characteristics were evaluated retrospectively in 104 patients recruited until July 2022 at baseline (T0) and over a maximum of 4 years (T4) of biologic therapy (omalizumab/OmaG = 41, from T0 to T4, mepolizumab/MepoG = 26, from T0 to T4, benralizumab/BenraG = 18, from T0 to T2, and dupilumab/DupiG = 19, from T0 to T1). Variations of parameters using means of paired Delta were assessed. Results: At baseline, patients had high prevalence of T2-driven comorbidities, low asthma control test (ACT mean 17.65 ± 4.41), impaired pulmonary function (FEV1 65 ± 18 %pred), frequent exacerbations/year (AEs 3.5 ± 3), and OCS dependence (60%). DupiG had lower T2 biomarkers/comorbidities and AEs, and worse FEV1 (57 ± 19 %pred) compared to other biologics (p < 0.05). All biologics improved ACT, FEV1%, FVC%, AEs rate, and OCS use. FEV1% improved in MepoG and BenraG over the minimal clinically important difference and was sustained over 4 years in OmaG and MepoG. A significant RV reduction in OmaG (T4) and DupiG (T1), and BenraG normalization (T2) of airflow limitation were found. We observed through inter-biologic parameters pair delta variation comparison a significant nocturnal awakenings reduction in BenraG vs. OmaG/MepoG, and neutrophils reduction in BenraG/DupiG vs. OmaG. Conclusions: Indirect comparison among biologics unveils clinical and functional improvements that may mark a different effectiveness. These results may highlight the preference of a single biologic compared to another with regard to specific treatable traits. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Due to its high prevalence, considerable morbidity, and chronicity, there is a need for the accurate in vivo evaluation of treatment efficacy. Line-field confocal optical coherence tomography (LC-OCT) is a new emerging imaging technique able to perform a non-invasive, real-time examination of the epidermis and the upper dermis. LC-OCT may represent a promising tool in the diagnosis and treatment follow-up of chronic eczematous skin diseases with barrier defects. Objectives: We aimed to investigate the role of LC-OCT in the non-invasive monitoring of the treatment effect on five patients with severe atopic dermatitis during dupilumab treatment. Materials and Methods: LC-OCT imaging was performed on five patients (three women and two men) aged between 14 and 85 years old at the baseline and at 2, 4, and 6 weeks of treatment with dupilumab. The LC-OCT scans were performed at two sites, the lesional skin in the antecubital fossa and the extensor part of the arm, considered a control site on each patient for comparison. The captured images were later evaluated. Descriptive statistics and a t-test were used to compare the analyzed parameters over time and between involved atopic skin and clinically healthy skin. Results: The LC-OCT imaging was able to detect the difference in stratum corneum (SC) thickness and quality and epidermal thickness (ET) and the changes before and after treatment with high accuracy. The main findings include a significant reduction in the epidermal and stratum corneum thickness and decreased epidermal spongiosis and inflammation, with better quality of the stratum corneum indicating restoration of its tightness at both lesional and control sites. Conclusions: This study demonstrates that clinical improvement of affected and unaffected atopic skin under dupilumab treatment correlates with the LC-OCT findings. LC-OCT represents a novel, non-invasive tool examining the in vivo skin barrier and inflammation and can help to monitor the treatment efficacy among patients with atopic dermatitis in daily practice. [ABSTRACT FROM AUTHOR]

Introduction: Dupilumab is the first biological treatment for atopic dermatitis (AD). Dupilumab-associated ocular surface disease (DAOSD) is one of the most commonly reported side effects in patients with AD during dupilumab treatment. This study aimed to identify risk factors for DAOSD in a real-world setting and construct a risk-scoring system for predicting DAOSD risk. Methods: A retrospective analysis was conducted for dupilumab-treated adult patients with AD between April 2019 and September 2023 at Yeouido St. Mary's Hospital in Korea. Patients aged =18 years who received dupilumab to treat AD were included. Univariate and multivariable logistic regression analyses were performed to determine independent risk factors for DAOSD. A risk scoring system was constructed to predict DAOSD risk based on the adjusted odd ratios of significant variables. Results: Of the 97 dupilumab-treated patients, 28 (28.9%) developed DAOSD. Among them, three (10.7%) patients discontinued dupilumab due to ocular side effects. In the multivariable analysis, older age, history of conjunctivitis, and a baseline Eczema Area and Severity Index (EASI) score =28 were independent risk factors for developing DAOSD. Using these variables, a risk-scoring system was constructed. The predicted DAOSD risks for AD patients with 0, 1, 2, 3, 4, and 5 points were 5.8%, 14.2%, 30.7%, 54.3%, 76.2%, and 89.6%, respectively. Conclusion: In this study, the patient's age, history of conjunctivitis, and higher baseline EASI score were significantly associated with DAOSD. This risk-scoring system would help identify high-risk patients requiring more caution when initiating dupilumab treatment. [ABSTRACT FROM AUTHOR]

IgE-mediated food allergy is characterized immunologically by a type 1 immune response triggered upon exposure to specific foods and clinically by a broad range of manifestations and variable severity. Our understanding of food allergy within the allergic march of atopic dermatitis (AD) is still incomplete despite the related risk of unpredictable and potentially severe associated reactions such as anaphylactic shock. The aim of this pilot study was to investigate the effects of dupilumab, an IL-4/IL-13 monoclonal antibody approved for AD, on the allergic sensitization profile of patients with AD and type 1 hypersensitivity-related comorbidities, including oral allergy syndrome, anaphylaxis, and gastrointestinal disorders. We conducted an observational pilot study with a longitudinal prospective design, enrolling 20 patients eligible for treatment with dupilumab. Laboratory exams for total serum IgE, specific IgE, and molecular allergen components were performed at baseline and after 16 weeks of therapy. Our results demonstrate a statistically significant decrease in molecular components, specific IgE for trophoallergens, and specific IgE for aeroallergens following treatment with dupilumab. We suggest that modulating type 2 immunity may decrease IgE-mediated responses assessed with laboratory exams and therefore could minimize allergic symptoms in polysensitized patients. Upcoming results of randomized controlled trials investigating dupilumab in food allergy are highly anticipated to confirm its potential effect in the treatment of IgE-mediated food allergies. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The indications for endoscopic modified Lothrop procedure (Draf 3) in patients with refractory chronic rhinosinusitis with nasal polyposis (CRSwNP) remain unclear. This study evaluates the effectiveness of Draf 3 for refractory CRSwNP focusing on improvements in disease severity and need for subsequent dupilumab rescue therapy.Retrospective review of patients with CRSwNP undergoing Draf 3 surgery at a tertiary center between 2012 and 2022. Clinicodemographic variables were compared across those who did versus did not require rescue with postoperative dupilumab. Time to postoperative dupilumab rescue was analyzed and longitudinal disease‐specific outcomes were measured using the sinonasal outcomes test (SNOT‐22).Within 87 patients with CRSwNP, 24.1% had aspirin‐exacerbated respiratory disease (AERD). Significant improvement in SNOT‐22 score was found in CRSwNP with AERD (p < 0.001) and without AERD (p = 0.01) up to 24 months postoperative. 14.9% eventually required rescue with a dupilumab. More specifically, of 21 patients with AERD, 24.1% eventually required rescue with dupilumab. Dupilumab rescue was associated with a greater number of prior sinus surgeries (p = 0.02), prior aspirin desensitization (p = 0.02), and worse preoperative Lund‐MacKay scores (p < 0.001). No association between biologic rescue and frontal recess antero‐posterior diameter was found (p = 0.20).Draf 3 surgery in CRSwNP was associated with significant improvement in SNOT‐22 score at 24 months. Furthermore, only 14.9% of patients required dupilumab rescue. Patients with AERD were more likely to require rescue with dupilumab even though 75.1% avoided treatment with the biologic over the study period. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent chronic inflammatory condition affecting the nose and paranasal sinuses, posing a significant socio‐economic impact with substantial challenges in management. Biologics targeting type 2 inflammation such as dupilumab, have emerged as promising options. This study addresses a critical knowledge gap by comprehensively evaluating the 3‐year impact of sustained dupilumab therapy in CRSwNP.A multicentric, retrospective collection of real‐world data from five tertiary referral centers in Germany was conducted, enrolling 150 adult patients. The study investigated patient‐reported outcomes, disease‐specific indices and clinical measures, focusing on therapeutic response persistence, adverse events, and factors influencing treatment continuity.Results indicate significant improvements in clinical parameters from baseline (n = 150) with sustained effectiveness after 36 months (n = 138) as indicated in mean score ± standard deviation. Dupilumab treatment significantly improved overall disease‐related impairment (VAS score: 7.5 ± 2.5 to 1.6 ± 1.3) and rhinosinusitis symptoms (SNOT‐22: 59.4 ± 19.4 to 18.0 ± 15.0). Nasal Polyp Scores (NPS) decreased (5.3 ± 1.8 to 0.7 ± 1.1), and olfactory function improved (3.2 ± 2.5 to 8.4 ± 2.8), with three out of four patients achieving normosmia or hyposmia after 36 months. An “Excellent” treatment response according to EUFOREA23 criteria was observed in 76.5% of patients after 36 months. Sixteen patients discontinued Dupilumab, 12 permanently. Adverse events totaled 69 in 48 patients, commonly self‐limiting.The study highlights the enduring effectiveness and lack of habituation to dupilumab after a sustained therapy of 3 years, providing valuable insights into its long‐term therapeutic implications for CRSwNP patients. [ABSTRACT FROM AUTHOR]

We present a case of a 47‐year‐old male with severe atopic dermatitis and metastatic renal cell carcinoma managed successfully with dupilumab. This case further supports the safety of dupilumab in patients with active malignancy, an area currently with limited data. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is a monoclonal antibody used for the treatment of moderate/severe atopic dermatitis (AD). In recent years, several studies have confirmed the positive association between AD and overweight/obesity, and a report demonstrated the effect of weight reduction on the improvement of AD symptoms. Methods: The weight of 170 patients under treatment with dupilumab was recorded at baseline and after 48 weeks (T48). Clinical monitoring was mainly conducted using the Eczema Area and Severity Index (EASI). The study aimed to assess a possible correlation between the clinical outcome of dupilumab therapy and BMI. Results: Although not statistically significant, patients with a BMI < 25 have a higher EASI percentage improvement than patients with a BMI ≥ 25 at any time point, and the percentage of overweight and obese patients that does not reach EASI-75 at T48 is higher compared to normal-weight patients (13.5% vs. 5.9%). Despite this, in the multivariate regression analysis, no baseline characteristic, including BMI, appears to increase the risk of not reaching EASI-75. In addition, the results show no differences in BMI between baseline and T48 in any age/sex group. Conclusions: The results suggest that overweight and obese patients have a lower response to dupilumab when considering the EASI score, but this difference does not appear to be clinically significant. Furthermore, dupilumab treatment does not seem to impact weight. [ABSTRACT FROM AUTHOR]

Background: Dupilumab has been shown to be an effective treatment in moderate‐to‐severe atopic dermatitis (AD) and severe asthma (SA). However, comparative real‐world analyses of adverse events (AE), particularly dupilumab‐associated ocular surface disease (DAOSD), are lacking. Objective: This is the first real‐world study to provide insight into the prevalence of AEs associated with dupilumab in AD compared with SA. Secondary objectives were to assess the prevalence, onset and therapeutic strategies of DAOSD and evaluate dupilumab discontinuation rates. Methods: Data from two daily practice registries including AD and SA patients receiving dupilumab treatment were analyzed. Adverse events, including DAOSD, were evaluated. Results: In total, 322 AD and 148 SA patients were included. Headaches (23.6%), injection site reactions (10.1%), and influenza‐like symptoms (13.5%) were more prevalent in SA patients. Interestingly, ocular AEs were significantly more prevalent in AD patients (62.1%, p < 0.001), including conjunctivitis (17.1%, p = 0.004). 88% AD and 47% SA patients with ocular AEs received one or more ophthalmic treatment(s). Additionally, 20% of AD and 17.6% of SA patients discontinued dupilumab treatment due to ocular AEs, while only 65% of these AD and none of these SA patients were referred to an ophthalmologist. Conclusion: The higher incidence of DAOSD in AD patients compared with SA patients in this real‐world study highlights the importance of physician awareness, especially when prescribing dupilumab to AD patients. Conversely, the findings of this study help alleviate potential concerns about ocular AEs in patients with SA who do not have comorbid AD. Furthermore, the effective management of most ocular AEs with ophthalmic treatments suggests favorable tolerability of dupilumab in daily practice, and multidisciplinary collaboration is essential to proactively manage ocular AEs before discontinuing dupilumab. [ABSTRACT FROM AUTHOR]

For dupilumab, real-world long-term follow-up data remain scarce, and studies on optimized treatment modes as well as drug survival rate and its predictors are lacking. To explore the effectiveness of different treatment modes of dupilumab and to understand the drug survival rates of dupilumab in China and its predictive factors. This retrospective study included patients with moderate-to-severe AD who received dupilumab treatment. Their clinical data were collected and analyzed. Compared with baseline, the SCORing Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), numerical rating scale (NRS), and Atopic Dermatitis Control Tool (ADCT) scores significantly decreased at 12, 24, and 52 weeks (p < 0.0001), and the continuous medication group had more significant improvements in SCORAD, EASI, NRS, and ADCT scores at 52 weeks than the noncontinuous medication group (p < 0.05). The 6-month and 1-year drug survival rates of dupilumab were 59.7% and 51.9%, respectively. The most common reason for treatment discontinuation was the satisfactory control of AD. Patients with adult-onset AD (adjusted odds ratio [OR]: 0.15, 95% confidence interval [CI]: 0.03–0.73) , not complicated by other systemic diseases (adjusted OR: 0.17, 95% CI: 0.04–0.84) and eosinophilia at baseline (adjusted OR: 3.71, 95% CI: 1.12–12.26) had a higher probability of drug discontinuation. In real-world practice in China, dupilumab has exhibited good long-term effectiveness and safety for the treatment of moderate-to-severe AD, and continuous administration can benefit patients in the long term. [ABSTRACT FROM AUTHOR]

This article discusses the use of dupilumab, a biologic medication, for the treatment of atopic dermatitis (AD) in pediatric and young adult patients with inborn errors of immunity (IEIs). The medication has been approved for use in children with moderate to severe AD who have inadequate control with topical therapies. The article presents case studies of patients with IEIs and AD who were treated with dupilumab, showing significant clinical improvement as early as week 4 of treatment. However, further studies are needed to evaluate the long-term safety and efficacy of dupilumab in this patient population. [Extracted from the article]

Eosinophilic esophagitis (EoE) is an increasingly prevalent immune‐mediated disease that leads to chronic changes in the oesophagus. These changes can include strictures, narrowing, and stenosis, mediated by an interleukin (IL)‐13 pathway, which leads to remodelling and fibrosis through increasing migration of fibroblasts and subepithelial fibrosis via collagen deposition 1. IL‐13 downregulates TSPAN12, a gene whose expression regulates fibrosis and causes changes in barrier function and higher rates of fibrostenosis in EoE. Dupilumab, a biologic therapy aimed at blocking IL‐13, has been shown to improve EoE‐related inflammation and fibrosis in clinical trials. We report here four unique patients with documented oesophageal stenosis with inability to pass a paediatric endoscope due to structuring disease, requiring dilation, who had resolution of their oesophageal narrowing following dupilumab therapy. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinits is a prevalent condition, affecting a substantial proportion of the population. This study investigates the impact of ongoing biologic therapy, specifically with Dupilumab, on allergy diagnostics in patients with allergic rhinits. Methods: Various tests, including the Skin Prick Test, serum IgE levels and Allergy Screening Panels, were examined for their effectiveness in detecting sensitizations during biologic treatment. Results: The results indicate a significant decline in total IgE levels following biologic therapy initiation, aligning with previous findings on Dupilumab's inhibitory effects on IL-4 and IL-13. However, the specific IgE to total IgE ratio for major allergens was not significantly reduced. Comparing diagnostic tools, the Skin Prick Test demonstrates an impressive retention rate of sensitizations (98%) during Dupilumab treatment, outperforming the Allergy Screening Panel, which shows a 75% detection rate. Notably, the panel displays limitations in capturing lower sensitization levels. Conclusion: In summary, this study underscores that, despite the influence of biologic therapy on certain markers, standard allergy tests remain viable while emphasizing the importance of considering specific IgE levels rather than relying solely on CAP classes. The Skin Prick Test in particular proves to be a reliable tool for identifying sensitizations during Dupilumab treatment. The results offer valuable guidance for the diagnostic management of Allergic rhinits in individuals subjected to Dupilumab treatment. [ABSTRACT FROM AUTHOR]

Introduction: Several clinical trials have established the efficacy and safety of dupilumab for treating atopic dermatitis (AD). However, literature remains scarce in reporting the long-term effectiveness, safety, and drug survival of dupilumab in real-world settings. This study aimed to describe the latter outcomes of dupilumab in patients with AD. Methods: This Portuguese, multicentric, observational, retrospective study included consecutive adult patients with AD who initiated dupilumab between January 2019 and September 2023, with a follow-up period up to 30 months. Drug discontinuation and adverse effects data were used to estimate drug survival. Clinical assessments included the Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), and Dermatology Life Quality Index (DLQI). Results: A total of 312 patients were included in the study, with 56.4% being male (median age of 30 years, range 18–83). The 30-month drug survival rate was 82.0%. During the study period, 12.5% of the sample (n = 39 patients) discontinued treatment: 7.3% due to treatment failure, 2.9% due to safety concerns, 1.3% due to complete disease control, 0.6% due to pregnancy, and 0.3% due to lack of compliance. Adverse events not leading to drug discontinuation were noted in 25.6% of the sample (n = 80). Conjunctivitis was the most frequently reported adverse event (17%), followed by facial erythema (9%). At 30 months, the mean EASI decreased significantly from 27.30 ± 11.89 at baseline to 2.92 ± 3.96 (p < 0.001), reflecting an overall improvement of 89.3%. Similarly, pruritus NRS decreased from 7.36 ± 1.90 at baseline to 1.74 ± 2.16 at month 30 (p < 0.001), improving by 76.4%, and mean DLQI changed from 18.0 ± 7.09 at baseline to 2.67 ± 3.95 at month 30 (p < 0.001), decreasing by 85.2%. Conclusions: This study increases our current understanding of dupilumab in real-world settings, demonstrating its long-term effectiveness and safety in treating AD. [ABSTRACT FROM AUTHOR]

Background: Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case series or case reports. This study aimed to analyze the efficacy of biologics for managing ABPA both qualitatively and quantitatively. Methods: All articles on APBA published in October 2023 were searched in PubMed, Web of Science, ClinicalTrials.gov, and Embase databases. The effects of interest were the mean changes from baseline for outcomes, including exacerbation rates, oral corticosteroids usage (OCS), and total immunoglobulin E (IgE) levels. Reported outcomes were quantitatively synthesized by usual or individual patient data (IPD) meta-analyses. PROSPERO registration number: CRD42022373396. Results: A total of 86 studies were included in the systematic review including 346 patients. Sixteen studies on omalizumab were pooled for the usual meta-analysis. Omalizumab therapy significantly reduced exacerbation rates (− 2.29 [95%CI − 3.32, − 1.26]), OCS dosage (− 10.91 mg [95%CI − 18.98, − 2.85]), and total IgE levels (− 273.07 IU/mL [95%CI − 379.30, − 166.84]), meanwhile improving FEV1% predicted (10.09% [95%CI 6.62, 13.55]). Thirty-one studies on dupilumab, mepolizumab, or benralizumab were pooled to perform an IPD meta-analysis, retrospectively. Both dupilumab and mepolizumab significantly reduced exacerbation rates, OCS, and total IgE levels. Benralizumab showed a similar trend, but it was not statistically significant. Tezepelumab showed weak evidence of its effects on ABPA. All five biologics led to milder clinical symptoms (e.g., cough, wheezing) with serious adverse effects that happened once in omalizumab treatment. Conclusion: These results indicate the clinical benefit of omalizumab, dupilumab, and mepolizumab in patients with ABPA. Further randomized, controlled studies with a larger sample size and longer follow-up are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Interleukin‐33 (IL‐33) is a proinflammatory alarmin cytokine released by damaged epithelial tissue cells that initiates and amplifies both type 1 and type 2 inflammatory cascades. A role for IL‐33 in atopic dermatitis (AD; a chronic, relapsing type 2 inflammatory disease of the skin) has been proposed. Itepekimab is a novel human IgG4P monoclonal antibody against IL‐33, currently in clinical development for chronic obstructive pulmonary disease (COPD). Two global phase II studies—a dose‐ranging itepekimab monotherapy study (NCT03738423) and a proof‐of‐concept study of itepekimab alone and in combination with dupilumab (NCT03736967)—were conducted in patients with moderate‐to‐severe AD to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy; both studies were terminated following an interim analysis of the proof‐of‐concept study, which failed to demonstrate the efficacy of itepekimab. In these two studies, itepekimab exhibited linear and dose‐proportional pharmacokinetics. Pharmacodynamics of total IL‐33 indicated that itepekimab saturated binding to the target in serum at 300 mg q2w and q4w doses, and decreased blood eosinophil counts. Concentration–time profiles of itepekimab and total IL‐33 were similar for itepekimab with or without dupilumab, and between East Asian and non‐East Asian subgroups. Itepekimab was generally well tolerated, both alone and in combination with dupilumab. The lack of clinical efficacy for itepekimab observed in these studies suggests that IL‐33 may not be a key pathogenic driver in moderate‐to‐severe AD. [ABSTRACT FROM AUTHOR]

Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. To evaluate patient-reported outcome measures (PROMs) and the safety of dupilumab in patients with moderate-to-severe AD over a follow-up period of up to 5 years. Data were extracted from the prospective, multicenter BioDay registry (October 2017–2022) of patients with moderate-to-severe AD treated with dupilumab in daily practice. In total 1223 patients, 1108 adults and 115 pediatric patients were included. After ≥1 year of treatment, mean Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numeric rating scale (NRS)-pruritus ranged between 7.8 and 8.7, 3.5 and 4.2, and 2.9 and 3.1 in adults, respectively, whilst these patient-reported outcome measures (PROMs) ranged between 8.9 and 10.9, 4.4 and 6.4, and 3.0 and 3.7 in pediatric patients, respectively. At follow-up, overall work impairment decreased from 40.1% to 16.3% to 13.3% in adults. Furthermore, class I obesity and itch-dominant patients generally had less favorable treatment response. Of all patients, 66.8% reported ≥1 adverse event, with conjunctivitis being the most common (33.7%). The overall percentage of missing values for selected PROMs was 26% in adults and 46% in pediatric patients. In addition to favorable safety, dupilumab has demonstrated sustained effectiveness across various PROMs, underscoring the treatment benefits from patients' perspectives. [ABSTRACT FROM AUTHOR]

Dupilumab, a human monoclonal antibody targeting the interleukin 4 alpha receptor, is used for treatment of moderate to severe atopic dermatitis (AD). Previous studies have reported diagnoses of cutaneous T cell lymphoma (CTCL) after dupilumab use. Investigate the risk of CTCL after dupilumab use in patients with AD. Using the TrinetX database, incidence of cutaneous and lymphoid malignancies including CTCL was compared between a cohort of patients with AD who used dupilumab and a cohort of patients with AD who never used dupilumab. A second analysis excluding prior disease-modifying antirheumatic drug use was performed. Propensity score matching was performed to control for covariates. An increased risk of CTCL was found in the cohort of AD patients who used dupilumab (odds ratio 4.1003, 95% confidence interval 2.055-8.192). The increased risk persisted after exclusion of prior disease-modifying antirheumatic drug use. Risk was not increased for other cutaneous or lymphoid malignancies. Most (27/41) cases of CTCL were diagnosed more than 1 year after dupilumab use. There is potential for misclassification in the database. Severity of AD could not be assessed. Association between dupilumab and CTCL does not prove causality. Dupilumab use is associated with an increased risk of CTCL in patients with AD in this cohort. [ABSTRACT FROM AUTHOR]

Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely. Our aim was to evaluate the antibody and cellular immunity after SARS-CoV-2 mRNA vaccination in patients on biologics (PoBs). Patients with severe asthma or atopic dermatitis who were taking benralizumab, dupilumab, or mepolizumab and had received the initial dose of the 2-dose adult SARS-CoV-2 mRNA vaccine were enrolled in a prospective, observational study. As our control group, we used a cohort of immunologically healthy subjects (with no significant immunosuppression) who were not taking biologics (NBs). We used a multiplexed immunoassay to measure antibody levels, neutralization assays to assess antibody function, and flow cytometry to quantitate Spike-specific lymphocytes. We analyzed blood from 57 patients in the PoB group and 46 control subjects from the NB group. The patients in the PoB group had lower levels of SARS-CoV-2 antibodies, pseudovirus neutralization, live virus neutralization, and frequencies of Spike-specific B and CD8 T cells at 6 months after vaccination. In subgroup analyses, patients with asthma who were taking biologics had significantly lower pseudovirus neutralization than did subjects with asthma who were not taking biologics. The patients in the PoB group had reduced SARS-CoV-2–specific antibody titers, neutralizing activity, and virus-specific B- and CD8 T-cell counts. These results have implications when considering development of a more individualized immunization strategy in patients who receive biologic medications blocking IL-4 or IL-5 pathways. [ABSTRACT FROM AUTHOR]

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Atopic dermatitis is a chronic inflammatory dermatosis characterized by pruritic, scaly, erythematous lesions. Its incidence varies but is estimated to be approximately 20% in children and between 7 and 14% in adults, with variation amongst countries. It is a multifactorial condition, with a complex interplay between genetic, immunological, and environmental factors. Research into the inflammatory response has identified new therapeutic targets that work to reduce inflammation and subsequently reduce flares. This study explores existing therapeutic agents for atopic dermatitis as well as newer therapies such as biologics and small molecules, drawing upon each agent's mechanism of action, relevant landmark clinical trials, efficacy, and safety profile. Current therapies include emollients, corticosteroids, cyclosporine A, calcineurin inhibitors, phototherapy, and methotrexate. Biologics described include dupilumab, tralokinumab, lebrikizumab, nemolizumab, and rocatinlimab. Small molecules inhibitors include Janus kinase inhibitors, phosphodiesterase 4 inhibitors, transient receptor potential vanilloid subfamily V member 1 antagonist, and aryl hydrocarbon receptor antagonist. [ABSTRACT FROM AUTHOR]

Background and Objectives: Atopic dermatitis is a chronic inflammatory skin disorder with a significant burden on patients' quality of life. This systematic review aims to evaluate the restoration of skin barrier abnormalities with interleukin-4/interleukin-13 (IL-4/IL-13) inhibitors and Janus kinase (JAK) inhibitors in atopic dermatitis. Materials and Methods: A comprehensive review of the literature was conducted, focusing on studies that assess the use of IL-4/IL-13 inhibitors and JAK inhibitors for atopic dermatitis. We identified eligible studies by searching Medline via PubMed with a special focus on their effect on the restoration of the epidermal barrier. Included studies evaluated the transepidermal water loss (TEWL), the reduction in epidermal thickness (ET), the improvement in ceramide synthesis, and the increase in stratum corneum hydration (SCH) with IL-4/IL-13 inhibitors and JAK inhibitors. The quality of included studies was assessed using the ROBINS-I and the RoB 2.0 tool for assessing the risk of bias. Results: Ten of the included studies concern dupilumab, while two concern JAK inhibitors. Ten were observational studies and two were randomized controlled trials (RCTs). The total number of included participants was 378 concerning dupilumab and 38 concerning JAK inhibitors. Five studies did not include any comparison group, three included healthy volunteers, two were conducted versus placebo, and two compared dupilumab with other treatments. The follow-up period ranged between 29 days and 32 weeks. The results demonstrated a significant decrease in transepidermal water loss (TEWL) and an increase in SCH on eczematous lesions for patients with sustained response to dupilumab treatment and observed improvements in ET and filaggrin (FLG) staining, which further support the efficacy of JAK inhibitors in enhancing skin barrier function. Conclusions: This review underscores the efficacy of IL-4/IL-13 inhibitors in improving skin barrier function. However, the limited number of studies focusing on JAK inhibitors and the overall lack of RCTs highlight the need for further research to establish the definitive role of IL-4/IL-13 inhibitors and JAK inhibitors in the restoration of the skin barrier. [ABSTRACT FROM AUTHOR]

Dupilumab is a biologic medication that is used for the treatment of moderate-to-severe atopic dermatitis (AD). Long-term data on dupilumab drug survival in Asia patients with AD are limited. A single-center, retrospective study was performed to assess drug survival between March 2019 and March 2023. Drug survival and associated characteristics were analyzed using Kaplan–Meier survival curves and multivariate Cox regression analysis, respectively. A total of 124 patients with AD (Mean age [standard deviation], 26.0 [8.6] years) with a 4 years-overall dupilumab drug survival rate of 87.9%, were included in this study. Characteristics associated with shorter drug survival were the low eczema area and severity index (EASI) scores at baseline (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.75–0.94, p-value = 0.003) and non-insurance coverage of dupilumab (HR 11.87; 95% CI 3.28–42.99, p-value = 0.001). This retrospective study demonstrated good overall 4-year dupilumab survival (87.6%) in South Korea. Patients with low baseline EASI scores and those who did not have insurance for dupilumab treatment discontinued the therapy frequently. To the best of our knowledge, this is the first long-term dupilumab drug survival study conducted in Asia with predictors. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Clinical trials and real‐life data have reported an increased incidence of conjunctivitis in patients treated with dupilumab for their atopic dermatitis (AD). Although mostly mild in severity, in some cases conjunctivitis will appear or increase after dupilumab initiation, which can lead to dupilumab discontinuation.(1) To describe the characteristics of patients developing conjunctivitis requiring discontinuation of dupilumab; and (2) to analyse the factors associated with a complete conjunctivitis improvement after dupilumab discontinuation and a switch to tralokinumab or Janus kinase inhibitors.This was a multicentre retrospective cohort study that included all patients with AD treated with dupilumab who developed conjunctivitis leading to dupilumab discontinuation and switching to tralokinumab or Janus kinase inhibitors in daily practice. Data on patients, their AD and conjunctivitis were analysed at the inclusion visit (corresponding to discontinuation of dupilumab and the institution of new AD treatment), at visit 2 (3–6 months after inclusion) and at visit 3 (corresponding to the last medical visit).After multivariate analysis, the only factors associated with a complete resolution of dupilumab‐associated conjunctivitis at visit 2 and/or visit 3 were conjunctivitis duration (OR 8.98, 95% CI 1.47–55) (p = 0.018), personal history of asthma (OR 10.66, 95% CI 1.82–62.63) (p = 0.009) and switching from dupilumab to Janus kinase inhibitors (OR 17.11, 95% CI 2.94–99.66) (p = 0.002).Although uncommon, severe dupilumab‐associated conjunctivitis is more frequent in daily life compared to its incidence in the dupilumab pivotal trials. In these cases, our study suggests that a rapid switch to another molecule, particularly a Janus kinase inhibitor, should be considered. [ABSTRACT FROM AUTHOR]

Our study aims to synthesize existing evidence of dupilumab for alopecia areata (AA) in pediatric patients with atopic dermatitis (AD). We searched MEDLINE and Embase on March 1, 2024, using keywords related to AD, AA, dupilumab, and pediatric patient populations per PRISMA‐ScR guidelines. A mean SALT score reduction of 42.6 following dupilumab treatment (p < .01) over an average of 3.21 months, and a mean reduction of Investigator Global Assessment (IGA) levels of 2.14 units (p < .01) demonstrates the efficacy of dupilumab in pediatric AA when there is concurrent AD. Our findings in combination with dupilumab's favorable safety profile in pediatric AD makes it an appealing option for AA treatment, however, a greater understanding of the underlying mechanisms, optimal pediatric patient selection criteria, long‐term efficacy, and safety profile of dupilumab in this context is warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: Eosinophilic otitis media, first reported in Japan, is a viscous, intractable otitis media often linked to bronchial asthma and chronic rhinosinusitis, characterized by highly viscous middle ear effusion. Its pathological mechanism remains unclear and the condition occasionally does not respond to steroids. It is now recognized as a rare type 2 inflammatory disease and should be treated specifically to enhance quality of life. This systematic review and meta-analysis evaluated the efficacies of biologic treatments. METHODS: We searched PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases up to September 2023. We retrieved ear examination findings, otitis media-related and symptom scores, air--bone gaps and hearing thresholds, serum eosinophil, and immunoglobulin E (IgE) levels before and after biologic treatments. RESULTS: Biologics treatment significantly improved subjective otitis media-related scores, compared with control group (standard mean difference (SMD) -1.62; 95% confidence interval (CI) [-2.24; -1.01], I² = 54%). Additionally, the serum eosinophil counts and IgE levels significantly decreased (SMD -1.40; 95% CI [-1.99; -0.81], I² = 0%) after 6-12 months of biologic treatments, but the hearing thresholds did not significantly change. There were no significant differences between groups treated with dupilumab and groups treated with other biologics. CONCLUSION: Biologics treatment for eosinophilic otitis media significantly improved subjective otitis media-related scores and decreased serum eosinophil and IgE levels, but no significant changes in hearing threshold. More randomized cohort studies are needed to confirm the efficacies of biologics in patients with refractory eosinophilic otitis media. [ABSTRACT FROM AUTHOR]

Key points A persistent type 2 endotype signature exists in recalcitrant chronic rhinosinusitis with nasal polyps mucosa on dupilumab. Revision sinus surgery immediately prior to dupilumab reduces long‐term interleukin (IL)‐4/IL‐13 tissue mRNA. Pre‐dupilumab revision surgery is associated with reduced tissue eosinophils and GATA‐3+ cells. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-4 and IL-13 are considered key drivers of type 2 inflammatory diseases. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for IL-4 and IL-13, thus inhibiting signaling of both cytokines. We report a case of a patient with uncontrolled severe asthma and other T2 inflammatory diseases (atopic dermatitis, chronic rhinosinusitis with nasal polyposis and eosinophilic esophagitis) treated with dupilumab. After one year of treatment, dupilumab improved asthma control together with lung function parameters and airway inflammation. Additionally, a positive impact on quality of life (QoL), evaluated by validated questionnaires, across all the diseases was observed. In this case report, a positive and objectively measurable of global improvement on QoL across all four T2 comorbidities was observed after treatment with dupilumab, demonstrating the important role of IL-4 and IL-13 and the existence of a unifying pathological mechanism in T2 diseases. [ABSTRACT FROM AUTHOR]

This article explores the impact of dupilumab, a monoclonal antibody used to treat atopic dermatitis, on food-specific immunoglobulin E (sIgE) levels in pediatric patients with moderate to severe atopic dermatitis. The study found that dupilumab led to a significant decrease in sIgE levels for various food allergens in these patients. This research is valuable for understanding the potential benefits of dupilumab in treating food allergies in young patients with atopic dermatitis. However, more research is needed to fully comprehend the effects of dupilumab in pediatric patients. [Extracted from the article]

Recalcitrant frontal sinusitis in patients with chronic rhinosinusitis and nasal polyps (CRSwNP) has a negative impact on their quality of life due to frontal pain and a high risk of sinus occlusion, thus necessitating antibiotics, systemic corticosteroids, and multiple surgeries. The aim of this study was to assess the efficacy of dupilumab in reducing frontal pain and the need for rescue treatments for recalcitrant frontal sinusitis in patients with CRSwNP. We enrolled a cohort of 10 patients with severe uncontrolled CRSwNP and concomitant recurrent frontal sinusitis associated with severe facial pain measured by MIDAS score who were treated with dupilumab 300 mg every 2 weeks and followed for at least 12 months. The mean MIDAS score decreased from 45.6 ± 10.7 at baseline to 1.3 ± 2.3 at 6 months (p < 0.05). VAS craniofacial pain decreased from 7.3 ± 1.6 at baseline to 1.2 ± 1.5 at 6 months (p < 0.05). No patient needed oral corticosteroids during treatment with dupilumab (p < 0.05), and the use of analgesics decreased from 9.6 ± 3.1 NSAID pills/week in the last 2 months at baseline to 0.6 ± 1.3 at 1 year of follow-up (p < 0.05). Our results demonstrated that use of subcutaneous dupilumab can improve symptom control, including recurrent severe cranio-facial pain, and reduce the need for rescue medical treatments (systemic steroids and NSAID) in patients with severe uncontrolled CRSwNP and concomitant recurrent frontal sinusitis. [ABSTRACT FROM AUTHOR]