Use Of Dupilumab Research Articles

Dupilumab for Chronic Hand Eczema: A Systematic Review and Meta-Analysis.

Chronic hand eczema (CHE) is a distressing and pervasive dermatologic condition, and effective treatment can be challenging. The novel IL-4/13 inhibitor dupilumab has shown clinical efficacy for atopic dermatitis (AD) and is being studied for CHE. PubMed database was searched for terms dupilumab and chronic hand eczema/dermatitis, including CHE subtypes (dyshidrotic, hyperkeratotic, allergic, contact, atopic, occupational, vesicular). Twenty-two study publications met inclusion and exclusion criteria for evaluation. Two multicenter prospective studies, one randomized controlled trial, two prospective observational studies, one retrospective study, nine case series, and seven case reports were included in the analysis with 374 total patients. Any partial response or complete resolution of CHE occurred in 80.3% of patients treated with dupilumab within 4-16 weeks of treatment. The patient response tended to increase throughout the duration of these studies for a significant percentage of patients, and for many it lasted beyond the study duration. Significant improvement in hand eczema severity scores and quality-of-life scores were noted. Efficacy was reported in over half of the cases of hyperkeratotic hand eczema; however, efficacy was decreased compared with relatively high consistent efficacy in other CHE subtypes such as dyshidrotic, vesicular, atopic, and contact CHE. Patients with current or previous AD had increased improvement scores compared to those without. The most common adverse effects were conjunctivitis (9.9%), herpes viral infection (1.4%), and facial erythema/dermatitis (1.3%). Dupilumab shows therapeutic efficacy in treating CHE. Further randomized controlled studies of dupilumab use in CHE subtypes are needed.

Dupilumab use in patients with hypereosinophilic syndromes: a multicenter case series and review of the literature

Dupilumab use in patients with hypereosinophilic syndromes: a multicenter case series and review of the literature

Maternal, Fetal, and Labour Outcomes of Dupilumab Use for Atopic Dermatitis During Pregnancy: A Systematic Review.

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.

Dupilumab-related late adverse events in patients with chronic rhinosinusitis with nasal polyps

Background Anti-IL-4 receptor α antibody (dupilumab) has demonstrated favorable sinonasal outcomes for chronic rhinosinusitis with nasal polyps (CRSwNP), which is mainly caused by type 2 inflammation. Although increased blood eosinophil levels and injection site symptoms are frequently observed as acute adverse events (AEs) of dupilumab, limited knowledge is available regarding the late AEs of dupilumab for CRSwNP. Objectives We investigated the late AEs following the initiation of dupilumab treatment for CRSwNP. Material and methods Fifty-one patients with CRSwNP treated with dupilumab for > 3 months were enrolled, and their clinical data were collected from their medical records. Results Six (11.8%) patients experienced late AEs. One case of eczema with pruritus, one case of psoriasis-like dermatitis, two cases of severe rash, one case of malignant lymphoma, and one case of alopecia areata were observed. Skin disorders were the most common late AEs in this study. It is a Th1-inflammatory disease, and its mechanism is thought to be due to the immune imbalance caused by dupilumab. We could not confirm whether malignant lymphoma in our case was caused by dupilumab use. Conclusions and significance Skin disorders are often late AEs associated with dupilumab; therefore, careful monitoring after dupilumab initiation should be considered.

Real-World Effectiveness and Use of Dupilumab in Eosinophilic Esophagitis.

Dupilumab, the first US Food and Drug Administration-approved treatment for eosinophilic esophagitis (EoE), lacks real-world data on use and effectiveness. We conducted a retrospective cohort study of 70 patients with EoE prescribed dupilumab, comparing prescriber type, indication, follow-up, and response. Indications varied with gastroenterologists commonly prescribing for treatment-refractory cases and allergists as first-line therapy. Endoscopic assessment was lacking in 25.9%, but those with follow-up showed high histologic remission (92.3% first-line and 85% previous treatment failure). Dupilumab demonstrates effectiveness across EoE severity, including milder disease without previous treatment failure. Improving follow-up and assessing cost-effectiveness will help clarify its role in the treatment algorithm.

Successful novel use of dupilumab for gastrointestinal involvement of idiopathic hypereosinophilic syndrome: case report and review of the literature.

Hypereosinophilic syndrome (HES) is characterized by blood and tissue hypereosinophilia leading to organ damage. Gastrointestinal involvement is the third most common manifestation. We present a patient with idiopathic HES with secondary eosinophilic esophagitis (EoE), gastritis, and enteritis, corticosteroids-dependent, azathioprine- and mepolizumab-refractory. The patient achieved clinical and histopathologic remission following dupilumab treatment. A 28year-old female presented with chronic episodic nausea and emesis since childhood and initial diagnosis of primary eosinophilic gastrointestinal disease (EGID), improved with corticosteroids, refractory to azathioprine. She was found to have peripheral eosinophilia and multifactorial anemia, with iron, B12, and folate deficiencies. Esophageal, gastric, duodenal, and terminal ileum biopsies showed significant eosinophilic infiltrate. Bone marrow biopsy at age 31 confirmed HES diagnosis. By age 32, she became total parental nutrition (TPN)-dependent. She failed trials of benralizumab and mepolizumab [anti-interleukin (IL)-5 inhibitors], and cromolyn (mast-cell stabilizer). After developing new esophageal stricture, we initiated dupilumab (IL-4/13 inhibitor), recently FDA-approved for EoE. After 9weeks, esophageal stricture, gut tissue eosinophilia, and prior intestinal ulcerations resolved. She ceased TPN and is tolerating a non-restricted diet, with complete symptom resolution. Our patient's complete remission with dupilumab shows promise for broadening its use in treating GI involvement in HES, along with primary EGIDs.

Cutaneous T-Cell Lymphoma and Dupilumab Use: A Multifactorial and Complex Story

Cutaneous T-Cell Lymphoma and Dupilumab Use: A Multifactorial and Complex Story

Rate of dupilumab use and symptom severity of patients with chronic rhinosinusitis with nasal polyposis after Draf 3 frontal sinusotomy.

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.

Dupilumab treatment in paediatric atopic dermatitis (2 to 18 years): Spanish multicentre retrospective real-life study.

Moderate-to-severe atopic dermatitis (AD) can be difficult to manage in paediatric patients, with few licensed treatments in this age group. Dupilumab is approved for AD in children older than 6 months. To assess the effectiveness and safety of dupilumab in a real-life cohort of paediatric AD patients in Spain. A multicentre, retrospective real-life study on the effectiveness and safety of dupilumab in patients aged 2 to 18 years old with moderate-to-severe AD was conducted. Demographic and clinical characteristics were analysed, and effectiveness (EASI, IGA, DLQI, NRS itch), safety, and drug survival measures were assessed. A comparison of our results with other real-world outcomes and with clinical trials was made. Data from 243 patients from 19 centres was collected, with a mean follow-up of 85 weeks. Dupilumab exhibited significant effectiveness, with marked reductions in severity scores from week 4. By week 16, 79.4% of patients reached EASI75 and 40.5% reached EASI90. Mean percentage reduction in EASI was 79.7%. Increasing improvements were observed until week 52, with 85.8% and 49.6% achieving EASI75 and EASI90, respectively. Forty-three patients developed adverse events (AE) (43/243, 17.7%), being the most frequent ocular surface diseases (20/243, 8.2%), injection site reactions (8/243, 3.3%) and facial redness (7/243, 2.9%). Drug survival was high (96.9% and 93.1% after 1 and 2 years of follow-up, respectively), with only 19 (19/243, 7.8%) patients interrupting treatment: 7 (7/243, 2.9%) due to AE, 2 (2/243, 0.82%) due to secondary failure, 5 (5/243, 2.1%) were lost to follow-up and 5 (5/243, 2.1%) entered remission and stopped treatment. Real-life use of dupilumab in paediatric AD showcased sustained effectiveness, high drug survival, and acceptable safety profiles. Longer-term studies are crucial for AE surveillance and how to manage disease remission.

Real-life management of atopic dermatitis patients with an inadequate response to on-label use of dupilumab

In patients with moderate to severe atopic dermatitis (AD) showing an inadequate response to dupilumab 300mg/2weeks, few real-life studies reported the response to alternative regimen maintaining dupilumab.To assess and analyze the response to an increased dose of dupilumab or its combination with cyclosporin A (CsA), methotrexate (MTX), or itraconazole (ITRA), all adult AD patients from 7 French University Hospitals were retrospectively included if they achieved an inadequate response to dupilumab 300mg/2weeks and were subsequently treated with an increased dose of dupilumab (300mg every 7 or 10 days), or a combination of dupilumab 300mg/2weeks with CsA, MTX or ITRA. The response after 3 months, along with epidemiological, clinical, and therapeutic baseline characteristics, were collected.Overall, 68.75% of the 48 included patients achieved an improved response, including 45.8% of complete response (CR). No strategy proved significantly better. Patients showing an initial no response never achieved a further CR versus 52.4% of patients with an initial partial response (p = 0.025). Digestive intolerance and tachycardia led to MTX and ITRA discontinuation in 3 patients.Increasing the dose of dupilumab or combining it with CsA, MTX, or ITRA could be alternative and safe options, to be evaluated in further medico-economic studies.

Real-world effectiveness of dupilumab versus benralizumab and mepolizumab.

Introduction: In the United States, this real-world study compared the effectiveness of dupilumab, benralizumab, and mepolizumab in reducing exacerbations and systemic corticosteroid (SCS) prescriptions among patients with asthma. Methods: Patients (≥12 years old) who initiated dupilumab, benralizumab, or mepolizumab (index) between November 2018 and September 2020 were identified by using electronic medical record data. Subjects were included if they had ≥ 12 months of data before and after the index date and two or more severe asthma-related exacerbations before the index date. Differences in baseline characteristics were addressed by using inverse probability treatment weighting (IPTW). Pairwise comparisons between dupilumab and benralizumab, or mepolizumab were conducted by using negative binomial regression, adjusting for baseline rates and unbalance characteristics (≥10% standardized differences) after IPTW. Results: Overall, a total of 1737 subjects met all criteria: 825 dupilumab, 461 benralizumab, and 451 mepolizumab initiators. In the postindex period, dupilumab was associated with a 24% and 28% significant reduction in the risk of severe asthma exacerbations versus benralizumab (incidence rate ratio [IRR] 0.76 [95% confidence interval {CI}, 0.67-0.86)] and mepolizumab (IRR 0.72 [95% CI, 0.63-0.82]), respectively. In addition, dupilumab treatment significantly reduced SCS prescriptions by 16% and 25% versus benralizumab and mepolizumab, respectively (p < 0.05). Conclusion: This study represents one of the largest real-world comparisons of biologics (dupilumab, benralizumab, and mepolizumab) for asthma in the United States to date. This analysis shows that the use of dupilumab was associated with a significantly greater reduction in both severe asthma exacerbations and SCS prescriptions compared with benralizumab and mepolizumab.

Use of Dupilumab in Pediatric Patients: A Review

Use of Dupilumab in Pediatric Patients: A Review

Cutaneous T-Cell Lymphoma after Dupilumab Use: A Real-World Pharmacovigilance Study of the FDA Adverse Event Reporting System

Cutaneous T-Cell Lymphoma after Dupilumab Use: A Real-World Pharmacovigilance Study of the FDA Adverse Event Reporting System

Dupilumab Safety and Efficacy up to 1 Year in Children Aged 6 Months to 5 Years with Atopic Dermatitis: Results from a Phase 3 Open-Label Extension Study.

Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management. The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE. In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg). Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0-5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator's Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores. Consistent with results seen in adults, adolescents, and older children (aged 6-11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population. ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B).

A Systematic Evaluation of Dupilumab for Bullous Pemphigoid Treatment

This paper systematically reviews the current articles regarding the use of dupilumab in the treatment of bullous pemphigoid (BP) to evaluate its safety and efficacy. PubMed, Embase, Cochrane Library, and Web of Science databases were searched for publications on dupilumab for BP from inception to 10 March, 2023. A total of 26 studies were included for systematic review. The primary outcome was clinical remission, and the secondary outcomes were recurrence and adverse events. Among 96 patients, 71.8% (n = 69/96) received systemic or topical steroids, immunosuppressants, immunomodulators, intravenous immunoglobulins, antihistamines, plasmapheresis, rituximab, and omalizumab, but none of them were successful. After dupilumab treatment, 66.7% (n = 64/96) of patients achieved complete remission, 25.0% (n = 24/96) had partial remission, 5.2% (n = 5/96) showed no remission, and no patients experienced deterioration. In addition, 1.0% (n = 1/96) and 2.0% (n = 2/96) patients stopped using dupilumab due to adverse reactions and cost, respectively. The average remission time was 4.5 months. 46.2% (n = 25/96) of the patients were followed up with a median follow-up of 8 months and only 2 patients relapsed at 8 and 7 months, respectively. Adverse event was 16.9% (n = 12/71), of which transient eosinophilia was the most common. This study indicates that the dupilumab is a promising treatment for BP with high clinical benefit associated with low recurrence rate, adverse event rate, and mortality. However, a large-scale randomized controlled trial is needed to further confirm the safety and efficacy of dupilumab in patients with BP treatment.

Corneal Complications Related to Dupilumab Use.

The aim of this report is to describe atypical corneal complications associated with dupilumab use. This is a series of four cases of adult patients with infiltrative or ulcerative keratitis secondary to dupilumab use. All four patients in this series were prescribed dupilumab for the treatment of atopic dermatitis and developed infiltrative or ulcerative corneal lesions. In all cases, corneal disease was successfully managed with immediate discontinuation of dupilumab and topical steroid treatment. In two cases, the patient also received antibiotic eye drops for infection precautions. Although dupilumab is most commonly associated with conjunctivitis, physicians should be aware of potential severe corneal complications for early identification and intervention.

Blood eosinophilia in patients with severe bronchial asthma and chronic polypous rhinosinusitis treated with dupilumab: A review

Bronchial asthma and chronic polypous rhinosinusitis are diseases associated with a T2-inflammatory immune response. These nosologies can be combined, creating the preconditions for a more severe course of multimorbidity, requiring the use of genetic engineering biological therapy. Dupilumab is a monoclonal antibody that can specifically bind to the alpha subunit of the interleukin-4 receptor and block the action of interleukins 4 and 13, which play a key role in the development of T2 inflammation. Numerous studies have demonstrated the high effectiveness of this medicament. The use of dupilumab in some cases may be accompanied by an increase in eosinophils in the blood. This article presents scientific base and our own experience in treating patients with dupilumab-associated eosinophilia, in addition we describe an algorithm for examining this group of patients for the purpose of timely diagnosis of diseases such as eosinophilic granulomatosis with polyangiitis, eosinophilic pneumonia, etc. It should be noted that in the most cases eosinophilia during targeted therapy with dupilumab is temporary and does not cause clinical manifestations.

Dupilumab therapy for atopic dermatitis is associated with increased risk of cutaneous T cell lymphoma: A retrospective cohort study

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 1year 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.

Outcomes of systemic Janus kinase inhibitors following prior dupilumab use for atopic dermatitis: An evidence-based review

Outcomes of systemic Janus kinase inhibitors following prior dupilumab use for atopic dermatitis: An evidence-based review

Global IL4Rα blockade exacerbates heart failure after an ischemic event in mice and humans.

Ischemic heart failure continues to be a highly prevalent disease among westernized countries and there is great interest in understanding the mechanisms preventing or exacerbating disease progression. The literature suggests an important role for the activation of interleukin-13 or interleukin-4 signaling in improving ischemic heart failure outcomes after myocardial infarction in mice. Dupilumab, a neutralizing antibody that inhibits the shared IL13/IL4 receptor subunit IL4Rα, is widely used for conditions such as ectopic dermatitis in humans. If global depletion of IL4Rα influences ischemic heart failure, either in mice or in humans taking dupilumab, is unknown. Here, we investigated the pathophysiological effects of global IL4Rα genetic deletion in adult mice after surgically induced myocardial infarction (MI). We also determined heart failure risk in patients with ischemic heart disease and concomitant usage of dupilumab using the collaborative patient data network TriNetX. Global deletion of IL4Rα results in exacerbated cardiac dysfunction associated with reduced capillary size after myocardial infarction in mice. In agreement with our findings in mice, dupilumab treatment significantly increased the risk of heart failure development in patients with preexisting diagnosis of ischemic heart disease. Our results indicate that systemic IL4Rα signaling is protective against heart failure development in adult mice and human patients specifically following an ischemic event. Thus, the compelling evidence presented hereby advocates for the development of a randomized clinical trial specifically investigating heart failure development after myocardial ischemia in patients taking dupilumab for another underlying condition.NEW & NOTEWORTHY A body of literature suggests a protective role for IL4Rα signaling postmyocardial infarction in mice. Here, our observational study demonstrates that humans taking the IL4Rα neutralizing antibody, dupilumab, have increased incidence of heart failure following an ischemic event. Similarly, global IL4Rα deletion in mice exacerbates heart failure postinfarct. To our knowledge, this is the first study reporting an adverse association in humans of dupilumab use with heart failure following a cardiac ischemic event.