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Background Methods Results Conclusion Despite increasing dupilumab use for chronic rhinosinusitis with nasal polyps (CRSwNP), little is known about the factors influencing its use in real‐world practice. We aimed to identify factors that may predict dupilumab prescription in CRSwNP patients who have undergone endoscopic sinus surgery (ESS).A single‐institution, retrospective cohort study of patients who underwent ESS for CRSwNP between 2015 and 2023 was conducted. Demographics, comorbidities, 22‐item sinonasal outcome test (SNOT‐22) scores, and dupilumab prescription date were extracted from patient records. Intraoperative nasal mucus cytokine levels were measured using a multiplex bead assay. Univariate logistic regression analysis was performed to identify factors associated with dupilumab prescription, and multivariate logistic regression was used to adjust for surgery date.A total of 299 CRSwNP patients were included, including seventy (23.4%) who were prescribed dupilumab postoperatively. Patients were more likely to be prescribed dupilumab if they had asthma (odds ratio [OR] 2.304), aspirin‐exacerbated respiratory disease (AERD, OR 3.375), elevated tissue eosinophils (OR 1.005), and higher 3‐month postoperative SNOT‐22 scores (OR 1.027). Patients prescribed dupilumab also had greater odds of having elevated mucus interleukin (IL)‐5 (OR 1.128) and IL‐13 (OR 1.213). When adjusting for surgery date, associated factors included: asthma (OR 2.444), AERD (OR 3.750), allergic rhinitis (OR 1.833), higher tissue eosinophils (OR 1.005), elevated 3‐month SNOT‐22 scores (OR 1.028), and higher IL‐5 (OR 1.123) and IL‐13 (OR 1.202) levels.Asthma, AERD, allergic rhinitis, and elevated tissue eosinophil, IL‐5, and IL‐13 levels are predictive of dupilumab prescription in CRSwNP patients. These may serve as clinical and inflammatory biomarkers and can aid in counseling patients about expected disease trajectory. [ABSTRACT FROM AUTHOR]

Key points: Dupilumab targets Th2‐associated inflammatory mediators to reduce disease burden in CRSwNP.While rare, potential sequelae include viral, helminth, and potentially amebic infections. [ABSTRACT FROM AUTHOR]

Freezing is essential for the stability of biological drug substances and products, particularly in frozen solution formulations and during the primary drying of lyophilized preparations. However, the unfrozen segment within the frozen matrix can alter solute concentration, ionic strength, and stabilizer crystallization, posing risks of increased biophysical instability and faster chemical degradation. While quantifying the unfrozen water content is important for designing stable biopharmaceuticals, there is a lack of analytical techniques for in situ quantitative measurements. In this study, we introduce a 1H magic angle spinning NMR technique to identify the freezing point (T ice) and quantify mobile water content in frozen biologics, applying this method to analyze the freezing of a commercial high-concentration drug product, Dupixent®. Our results demonstrate that water freezing is influenced by buffer salt properties and formulation composition, including the presence of sugar cryoprotectants and protein concentration. Additionally, the 1H chemical shift can probe pH in the unfrozen phase, potentially predicting the microenvironmental acidity in the frozen state. Our proposed methodology provides fresh insights into the analysis of freeze-concentrated solutions, enhancing our understanding of the stability of frozen and lyophilized biopharmaceuticals. [Display omitted] [ABSTRACT FROM AUTHOR]

Key points: In 2021, Medicare spending on biologics was $926 million in Part B (FFS) and $1.3 billion in Part D (FFS/MA).Between 2017 and 2021, annual Medicare spending on biologics increased by approximately 200%.Between 2023 and 2025, Medicare Part D OOP costs for biologics will decrease by an estimated 50%–60%. [ABSTRACT FROM AUTHOR]

Dupilumab has emerged as an effective treatment option for those suffering from moderate-to-severe atopic dermatitis (AD). Since its approval in 2017 by the United States Food and Drug Administration, dupilumab demonstrated efficacy in a wide range of "off-label" dermatologic conditions. With its increasing use, dermatologists must navigate prescribing dupilumab in complex patient populations. To that end, we performed a single-institution, retrospective, case-series study to assess efficacy, tolerability, and safety of dupilumab in elderly, patients on concomitant immunosuppressive/immunomodulating therapies, and those with pre-existing co-morbidities (e.g., malignancies, chronic renal and/or liver diseases, organ transplantation, hematologic malignancies, and infection). We conducted chart reviews of 248 patients who were prescribed dupilumab between January 1, 2017 and August 31, 2021, and identified 64 patients who met the criteria of being in the complex patient group as described above. Our results showed that 87.5% (56/64) of complex patients demonstrated improvement and/or disease clearance on dupilumab. 20.3% (13/64) of them experienced one or more side effects reported as conjunctivitis, seborrheic dermatitis, psoriasiform eruption, xerosis, facial burning sensation, anaphylactic reaction/angioedema, and worsening of AD. 9.4% (6/64) of them discontinued dupilumab due to the side effects. These findings demonstrated that dupilumab can be safely considered in certain complex patient populations such as elderly and those with significant pre-existing co-morbidities and can be safely combined with immunosuppressive medications and/or other biologic therapies. In the future, more studies with long-term follow-up are needed to validate the efficacy and safety of dupilumab in these challenging patients with complex medical histories. [ABSTRACT FROM AUTHOR]

Hypereosinophilic syndrome describes a process in which eosinophils in the peripheral blood are persistently increased, with variable clinical manifestations. Finding efficacious treatments for this disease can be challenging. This case describes a 72‐year‐old man with idiopathic hypereosinophilic syndrome with cutaneous manifestations who was successfully treated with dupilumab as a single agent therapy. There was complete clinical and biochemical resolution of disease (eosinophils levels decreased from 4.13 to 0.92) without complications. [ABSTRACT FROM AUTHOR]

Dupilumab is a fully human monoclonal IgG4 antibody directed against the alpha subunit of the IL-4 receptor and prevents the signaling of IL-4 and IL-13, two type 2 cytokines known to be important drivers of atopic diseases. In March of 2017, the United States Food and Drug Administration (FDA) approved dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults that is uncontrolled with topical medications, becoming the first biologic agent approved to treat this chronic skin condition. In October of 2018, Dupilumab received approval by the FDA as an add-on maintenance therapy in patients with moderate-to-severe asthma aged 12 years or older with an eosinophilic phenotype or with oral corticosteroid-dependent asthma. This review summarizes the characteristics of dupilumab and the clinical research that has been published to date, including treatment efficacy and adverse events.

Tumor-associated macrophages (TAMs) are an abundant tumor-promoting cell type in the tumor microenvironment (TME). Most TAMs exhibit a pro-tumor M2-like phenotype supportive of tumor growth, immune evasion, and metastasis. IL-4 and IL-13 are major cytokines that polarize macrophages to an M2 subset and share a common receptor, IL-4 receptor alpha (IL-4R alpha). Treatment of human ex vivo polarized M2 macrophages and M2 macrophage precursors with IL-4R alpha antagonist antibody Dupilumab (DupixentⓇ) reduces M2 macrophage features, including a shift in cell surface marker protein expression and gene expression. In animal models of prostate cancer, both pharmacologic inhibition of IL-4R alpha and genetic deletion of IL-4R alpha utilizing an Il4ra -/- mouse model result in decreased CD206 on TAMs. These data support IL-4R alpha as a target to reduce the pro-tumor, M2-like macrophage phenotype as a novel adjunct cancer therapy.

Atopic dermatitis is a chronic complex inflammatory disease that significantly impacts maternal well-being and quality of life during pregnancy, warranting effective therapeutic interventions that prioritize maternal health and fetal safety. Dupilumab is approved for moderate-to-severe atopic dermatitis, but limited data exist regarding its safety during pregnancy. We conducted a systematic review to review and analyze maternal, fetal, and labour outcomes in patients receiving dupilumab for atopic dermatitis during pregnancy. Comprehensive searches were conducted using databases including OVID, Scopus, and Web of Science, covering studies published until May 2024. Our search yielded 285 studies, of which 13 met the eligibility criteria. These studies included 68 patients with 69 pregnancies, revealing 58 live births and 11 spontaneous abortions. Dupilumab therapy was administered continuously throughout pregnancy in 22.2% of cases, while 77.8% received intermittent treatment. Maternal atopic dermatitis outcomes showed significant improvement in disease severity. Most pregnancies (86.3%) progressed without complications. Labour-associated outcomes varied, with 82.4% of women undergoing vaginal deliveries. The majority of births occurred at full term (82.5%), with a mean gestational age of 38.4 weeks. Fetal outcomes demonstrated a normal birth weight in 92.3% of cases, with no reported congenital defects. Our review suggests that dupilumab use during pregnancy is associated with improvement of atopic dermatitis and low or minimal risk of major adverse outcomes in treated patients or their newborns. Prospective studies with long-term follow-up are warranted to confirm the safety of dupilumab in this population. [ABSTRACT FROM AUTHOR]

Urmi Mehta,1,2 Marjan Farid1 1Gavin Herbert Eye Institute, Department of Ophthalmology, University of California, Irvine, CA, 92697, USA; 2Western University of Health Sciences, Pomona, CA, 91766, USACorrespondence: Marjan FaridGavin Herbert Eye Institute, University of California, Irvine, CA, USATel +1 949 824-2020Email mfarid@hs.uci.eduAbstract: Dupilumab is a monoclonal antibody that is used for the treatment of atopic dermatitis (AD) in adults. However, increasing reports of ocular complications including conjunctivitis and dry eye disease have been documented. In this report, we describe a case of a patient who developed limbal stem cell deficiency (LSCD) after prolonged Dupilumab use. A 56-year-old Caucasian male with a history of AD presented with gradual onset cloudy vision and extensive diffuse symblepharon resulting from Dupilumab treatment. He was diagnosed with cicatrizing blepharoconjunctivitis and secondary LSCD after slit lamp examination. In conclusion, LSCD secondary to cicatricial disease is a severe adverse ocular complication caused from long-term Dupilumab treatment.Keywords: limbal stem cell disease, symblepharon, cicatrizing blepharoconjunctivitis, Dupilumab, dupixent

Abstract Treatment options for severe CRSwNP are limited. Dupilumab is a safe, well‐tolerated, and effective alternative in patients with poor control of symptoms, corticosteroid‐dependent disease, and high rates of recurrence of nasal polyps after surgery.

Background: Consensus is that immunoglobulin IgG4 contains only N-linked glycosylation. The analysis of several batches of commercial biopharmaceutical product Dupixent using top-down intact mass spectrometry revealed that this IgG4 features a small amount of O-linked glycosylation in the Fab region. This is the first report of an O-linked glycosylation in an IgG4 antibody., Methods: Monoclonal antibody solutions were subjected to cation exchange (CEX) and reverse phase (RP) chromatography and/or additional preconcentration/fractionation methods to prepare samples for subsequent analysis. Advanced MS analysis and fragmentation techniques (HCD, ETD, and EThcD) were employed to localize the O-linked glycosylation as well as elucidate the structure of the glycan(s)., Results: O-linked glycosylation in the IgG4 dupilumab was discovered by intact-MS. The probable location was narrowed down to four sites in the CH1 domain, and the structure of the O-linked glycan was determined to be of Core 1 type. The relative quantities of the modifications were low, but the glycosylation was consistently detected in several batches of Dupixent., Conclusions: We discovered a rare glycosylation modification on dupilumab, an IgG4 antibody. The O-linked glycosylation was characterized and localized in the Fab region., (© 2024 Sandoz Deutschland. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Dupilumab is a fully human monoclonal IgG4 antibody directed against the alpha subunit of the IL-4 receptor and prevents the signaling of IL-4 and IL-13, two type 2 cytokines known to be important drivers of atopic diseases. In March of 2017, the United States Food and Drug Administration (FDA) approved dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults that is uncontrolled with topical medications, becoming the first biologic agent approved to treat this chronic skin condition. In October of 2018, Dupilumab received approval by the FDA as an add-on maintenance therapy in patients with moderate-to-severe asthma aged 12 years or older with an eosinophilic phenotype or with oral corticosteroid-dependent asthma. This review summarizes the characteristics of dupilumab and the clinical research that has been published to date, including treatment efficacy and adverse events.

Dupilumab is a biologic approved by the United States Food and Drug Administration (US FDA) for the treatment of atopic dermatitis. While it is an effective medication for eczema, ocular side effects are common in patients receiving dupilumab therapy. Greater consideration is needed when evaluating these individuals for corneal refractive surgery. Dupilumab patients may suffer from atopy, a condition that also merits consideration in those desiring refractive surgery. Additional testing and careful consideration are needed, as these patients have an increased risk of dry eye syndrome, keratoconus, cataracts, diffuse lamellar keratitis, viral keratitis, and perioperative infection. This commentary discusses the current understanding of dupilumab ocular side effects and investigates factors to consider when evaluating these patients for corneal refractive surgery. [ABSTRACT FROM AUTHOR]

Treatment options for severe CRSwNP are limited. Dupilumab is a safe, well‐tolerated, and effective alternative in patients with poor control of symptoms, corticosteroid‐dependent disease, and high rates of recurrence of nasal polyps after surgery. [ABSTRACT FROM AUTHOR]

Dupilumab is a recombinant human immunoglobulin G (IgG) 4 monoclonal antibody that inhibits interleukin-4 and interleukin 13 signallings. Dupilumab has been approved in the United States (US) and Canada for the treatment of moderate-to-severe atopic dermatitis (AD), moderate-to-severe asthma and chronic rhinosinusitis with nasal polyps, and additionally in the US for eosinophilic esophagitis and prurigo nodularis. Data on the safety of dupilumab exposure during pregnancy is limited. This is a North American-based registry study designed to monitor pregnancy and infant outcomes among women in the US and Canada exposed to dupilumab when used to treat moderate-to-severe AD and moderate-to-severe asthma. The primary data collected from this prospective post-marketing pregnancy registry will allow for a better understanding of any effects of dupilumab exposure on pregnancy and infant outcomes in a real-life clinical setting. Presented is an overview of the study design and interim recruitment into this pregnancy study. The study will assess the risks of major structural birth defects, spontaneous abortion, elective termination, stillbirth, preterm delivery, the pattern of three or more minor structural defects, small for gestational age, postnatal growth at approximately 1 year of age, and serious or opportunistic infections in the first year of life in pregnancies exposed to dupilumab compared to a disease-matched comparison (DC) group and a healthy comparison (HC) group. This OTIS research study is a North American, prospective cohort study comparing pregnancy outcomes in participants exposed to dupilumab for asthma and/or atopic dermatitis to a DC group with asthma and/or atopic dermatitis without dupilumab exposure, and to an HC group. Participants exposed to dupilumab during pregnancy who do not meet the eligibility criteria are enrolled into a ‘case series’ and these data may be used to further inform on the safety of dupilumab. Recruitment began in October 2018 and will continue through October 2023, with a goal of 500 participants in the cohort study (200 dupilumab-exposed, 200 DC and 100 HC). The study captures data on exposures, outcomes and covariates through maternal interviews and maternal and pediatric medical records, and a pediatric dysmorphology exam. Disease severity is measured by maternal questionnaires and patient-reported disease severity scales. Between 24 October 2018 and 1 November 2022, 354 participants were enrolled in the cohort study, 144 Dupilumab-exposed, 134 DC and 76 HC. An additional 28 participants were enrolled in the dupilumab case series group. The most common reason for enrollment into the case series was retrospective enrollment, followed by having an indication other than AD or asthma and having exposure prior to the last menstrual period. The publication of this data will help healthcare professionals and their patients make informed treatment decisions during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a common inflammatory disease caused by a type 2 T helper cell-mediated immune response to environmental antigens. Approximately 1 in 5 patients with AD presents with moderate to severe disease, and treatments approved by the Food and Drug Administration include emollients, topical glucocorticoids, and calcineurin inhibitors. Dupilumab, a fully human monoclonal antibody, improves AD via inhibition of interleukin-4 and interleukin-13., Objective: Our aim was to characterize the prescribing patterns of dupilumab for AD in adults at a large university-affiliated health system., Methods: A retrospective, observational cohort study was conducted using electronic data from the Observational Health Data Sciences and Informatics database, assessing data from the University of Colorado Medical Campus and its affiliates. The outcome measured was the prevalence of dupilumab prescribed for adults with AD (n=6421), between March 28, 2013, and March 28, 2021. We assessed whether the characteristics of patients who received dupilumab were different from those who did not. Each patient characteristic was assessed using a univariate logistic regression with the binary outcome of receiving or not receiving dupilumab., Results: We found a population prevalence of 5.6% (6421/114,476) for AD. In our cohort, Black patients with AD were more than twice as likely to have received dupilumab compared to White patients (odds ratio 2.352, 95% CI 1.58-3.39). Patients with a diagnosis of atopic neurodermatitis were approximately twice as likely to have received dupilumab compared to those with other diagnostic variants of AD (odds ratio 1.87, 95% CI 1.01-3.22)., Conclusions: Our results demonstrate that both patient racial characteristics and specific AD diagnoses were associated with variations in dupilumab prescription patterns., (©Torunn E Sivesind, Ani Oganesyan, Grace Bosma, Camille Hochheimer, Lisa M Schilling, Robert Dellavalle. Originally published in JMIR Dermatology (http://derma.jmir.org), 30.08.2023.)

Dupilumab is one of a number of biologics currently under investigation for the treatment of eosinophilic esophagitis (EoE). We report on a group of 7 pediatric and young adult patients with EoE who were treated with dupilumab for a primary indication of asthma or atopic dermatitis, all of whom previously failed swallowed topical corticosteroid therapy dietary for management of their EoE. All 7 patients demonstrated histologic improvement in their EoE while on dupilumab, with a drop in median peak esophageal eosinophil count from 50 eosinophils per high-powered field (eos/hpf) (IQR 48-95 eos/hpf) to 2 eos/hpf (IQR 0-5 eos/hpf) off swallowed topical corticosteroid. Additionally, improvements in EoE symptoms and endoscopic findings were noted. This report highlights the effectiveness of dupilumab in a group of multiply atopic pediatric and young adult patients with difficult-to-treat EoE in real world practice., Competing Interests: The author’s institution is a study site for phase 3 trials entitled “A randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of dupilumab in pediatric patients with active eosinophilic esophagitis” sponsored by Regeneron Pharmaceuticals. While the authors will be listed as sub-investigators in this trial, neither author is receiving financial compensation from this study, nor do they have any other competing financial interests., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)