Efficacy Of Dupilumab Research Articles

43916 Efficacy and Safety of Abrocitinib and Dupilumab in Patients With Moderate-to-Severe Atopic Dermatitis in the Presence or Absence of Comorbid Asthma or Allergic Rhinitis: A Post Hoc Pooled Analysis of JADE COMPARE and JADE DARE

43916 Efficacy and Safety of Abrocitinib and Dupilumab in Patients With Moderate-to-Severe Atopic Dermatitis in the Presence or Absence of Comorbid Asthma or Allergic Rhinitis: A Post Hoc Pooled Analysis of JADE COMPARE and JADE DARE

42002 Clinical efficacy and safety of Dupilumab for the treatment of moderate to severe atopic dermatitis in Korea

42002 Clinical efficacy and safety of Dupilumab for the treatment of moderate to severe atopic dermatitis in Korea

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

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

Efficacy and safety of new systemic therapies in moderate-to-severe atopic dermatitis in the elderly: meta-analysis

Objective: To systematically evaluate the efficacy and safety of new systemic therapies (biological agents and JAK inhibitors) in moderate-to-severe elderly atopic dermatitis. Methods: The database of Embase, PubMed, Web of Science,Cochrane, the Global Resource of Eczema Trials database, ClinicalTrials. Gov, CNKI, Wanfang, VIP were used to search for literatures of randomized controlled trials (RCTs) and real-world studies of the treatment of moderate-to-severe AD with the new systemic therapies from January 2014 to February 2023. Two reviewers independently screened the literature, extracted the data and evaluated the risk of bias included in the study. Data were analyzed by Review Manager 5.3 software for meta-analysis and odds ratio (OR) and 95% confidence interval were used as the effect statistics. The heterogeneity and publication bias were assessed. Results: A total of five studies (523 elderly patients and 802 young patients) using dupilumab were included for meta-analysis. Dupilumab showed good efficacy in elderly AD, with 74.6%(390/523) of patients whose EASI reached 75, which there was no significant difference with young patients (OR=0.79, 95%CI:0.58-1.07, P=0.122); the proportion of elderly patients with NRS improvement≥4 was 68.7%(244/355), and there was no significant difference with young patients (OR=0.79, 95%CI:0.55-1.14, P=0.213). The most common adverse reactions were conjunctivitis, facial and neck erythema and injection site reactions, and there are no serious adverse events in both groups. The incidence of adverse events in elderly patients was 24.3%(65/267), which was not significantly different from that in young patients (OR=1.07, 95%CI:0.65-1.77, P=0.789). There are few studies on other biological agents and JAK inhibitors in elderly AD patients. We only found 4 studies of elderly AD patients using JAK inhibitors (2 studies on abrocitinib and 2 studies on upadacitinib). The clinical efficacy of abrocitinib in the elderly was not significantly different from that in the young. The incidence of serious adverse events of abrocitinib and upadacitinib increased in the elderly and was dose-related. Conclusion: The efficacy and safety of dupilumab in elderly AD patients were similar to those in the young patients, and the JAK inhibitor needs to be further studied and verified.

Efficacy and Safety of Dupilumab in Older Patients (Aged 80 Years and Above) with Atopic Dermatitis: A Prospective Study.

Atopic dermatitis presents unique challenges in the older population owing to age-related changes in skin barrier function and immune regulation. However, there is limited evidence on the efficacy and safety of dupilumab, an anti-interleukin-4Rα monoclonal antibody, in patients with atopic dermatitis aged 80 years and above. We aimed to assess the clinical efficacy and safety of dupilumab treatment in patients with atopic dermatitis aged 80 years and above. Twenty-eight older patients received dupilumab and were evaluated based on several clinical parameters, including the Eczema Area and Severity Index (EASI), Numeric Rating Scale (NRS), Dermatology Life Quality Index (DELI), and AD Control Tool (ACT). Safety assessments and monitoring of concomitant medication use were conducted. Twenty-six patients completed 16 weeks of treatment, 13 completed 28 weeks, and two completed more than 36 weeks. Dupilumab treatment resulted in a significant improvement in atopic dermatitis symptoms after 16 weeks as demonstrated by reduced EASI, NRS, DLQI, and ADCT scores. Dupilumab had no significant impact on underlying diseases or medication use. No common adverse reactions, such as conjunctivitis and erythema of the face and neck, were identified. Among the 26 patients receiving dupilumab treatment during the COVID-19 pandemic, 17 remained uninfected or experienced milder COVID-19 symptoms than experienced in the general population. Dupilumab treatment showed significant efficacy in improving atopic dermatitis symptoms in patients aged 80 years and above with a high level of safety. Larger long-term clinical trials are needed to validate these results and provide further evidence for the use of dupilumab in older patients with atopic dermatitis.

Prevalence of type 2 inflammatory signatures and efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps from two phase 3 clinical trials: SINUS-24 and SINUS-52.

This post hoc analysis of the international SINUS-24/-52 trials (NCT02912468/NCT02898454) aimed to assess dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) according to different definitions of type 2 inflammatory signature. Six definitions of type 2 inflammation were used: ≥150 eosinophils/μL or total immunoglobulin E (IgE)≥100IU/mL with a coexisting type 2 condition; ≥150 eosinophils/μL or total IgE≥100IU/mL; ≥150 eosinophils/μL; ≥250 eosinophils/μL or total IgE ≥100IU/mL; coexisting asthma or ≥300 eosinophils/μL; presence of a coexisting type 2 condition. Odds ratios (ORs; dupilumab vs. placebo) for achieving clinically meaningful improvement (≥1 point) from baseline to week 24 (pooled SINUS-24/-52) and week 52 (SINUS-52) were calculated for nasal polyp score (NPS; range 0-8), nasal congestion/obstruction score (NC; 0-3), and loss of smell score (LoS; 0-3). At baseline (n=724), most patients displayed a type 2 inflammatory signature across definitions (64.2%-95.3%). At week 24, ORs for clinically meaningful improvement ranged from 11.9 to 14.9 for NPS across type 2 definitions, 6.5-9.6 for NC, and 12.2-17.8 for LoS (all p<0.0001). OR ranges were similar or greater at week 52: 19.0-36.6, 7.6-12.1, and 9.2-33.5, respectively (all p<0.0001). Most patients with CRSwNP in the SINUS study had type 2 inflammation. Dupilumab demonstrated robust efficacy across definitions of type 2 inflammation, consistent with its profile as an inhibitor of Interleukin-4 and Interleukin-13 signaling, key and central drivers of type 2 inflammation in CRSwNP. This study assessed type 2 inflammation prevalence and dupilumab efficacy in chronic rhinosinusitis with nasal polyps according to algorithm-defined type 2 inflammation Dupilumab efficacy was similar across all type 2 definitions.

Efficacy of Dupilumab in Patients with Atopic Dermatitis and Alopecia Areata: A Case Series

Efficacy of Dupilumab in Patients with Atopic Dermatitis and Alopecia Areata: A Case Series

Assessment of the efficacy and safety of dupilumab combined with cyclosporine A in patients with atopic dermatitis

Purpose: To assess the efficacy and safety of dupilumab combined with cyclosporine A in patients with atopic dermatitis.Methods: This retrospective study enrolled 100 patients with atopic dermatitis who received treatment at Beijing Luhe Hospital between November 2020 and November 2022. The patients were randomly divided into two groups, namely, treatment group and comparison group, with 50 cases in each group. Comparison group received cyclosporine A, while the treatment group received dupilumab in addition to cyclosporine A. The various fficacy scores and adverse reactions between the two groups were recorded and compared.Results: After treatment, skin lesion area and severity, EASI score, NRS score, SCORAD score, POEM score and DLQI score in the treatment group were significantly lower than those in the comparison group (p &lt; 0.05).Conclusion: The combination of dupilumab and cyclosporine A significantly alleviates the symptoms of acne and pruritis, as well as reduce the area of skin lesions in patients with atopic dermatitis. This treatment also enhances the quality of life of the patients. However, further but larger clinical trials are required prior to adoption of this combination treatment in clinical practice.

Real-life long-term efficacy of dupilumab in adults with moderate to severe atopic dermatitis: Results of a cohort study

Real-life long-term efficacy of dupilumab in adults with moderate to severe atopic dermatitis: Results of a cohort study

Dupilumab improve acquired reactive perforating collagenosis characterized by type 2 inflammation.

Acquired reactive perforating collagenosis (ARPC) is a clinically challenging disease with an unclear pathogenesis. To evaluate the efficacy and safety of dupilumab for the treatment of ARPC, and analyze the expression of type 2 inflammation-related molecules in ARPC lesions. This retrospective cohort study included 20 patients with ARPC; 10 received dupilumab and 10 received conventional therapy. The efficacy and safety of dupilumab were evaluated at 12 weeks. Immunohistochemical and immunofluorescence analyses of T- and B-cell markers, and type 2 inflammation-related cytokines, were performed on skin samples from ARPC patients, atopic dermatitis (AD) patients, and healthy controls. Significantly more patients showed improvements in the Investigator Global Assessment score (100% vs. 0%; p < 0.0001) and itching (90%/8.33%, P =.001) in the dupilumab group compared to the conventional group at 12 weeks. There were no adverse effects in the dupilumab group. The ARPC lesions showed enhanced dermal infiltration of CD3+ T-cells, with a predominance of Th2 cells, similar to AD lesions. IL-4 and IL-13 were co-localized with GATA3 in ARPC lesions. Dupilumab improved ARPC charaterized with type 2 inflammation.

Effectiveness of Dupilumab in the Treatment of Adult and Older Adult Patients with Severe, Uncontrolled CRSwNP.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial disease that significantly impacts patients' quality of life. New therapeutic strategies and in particular biologic treatments are now available for these patients. It has been demonstrated that Dupilumab (an anti IL-4/IL-13 biologic drug) is effective in reducing the size of nasal polyps and in improving patients' symptoms and thus, quality of life. No real-world studies examining Dupilamab's efficacy in the elderly with respect to other adult age groups have as yet been carried out. The aim of this multicentric study was to evaluate Dupilumab's efficacy in young-middle adults as opposed to an older adult population affected by severe, uncontrolled CRSwNP. Of the 96 patients included in the study, 22 were 65 years old or older. Significant improvements were observed in all the parameters considered in both age groups after treatment was begun (T0 mean values for SNOT-22 = 58.5 ± 20.3, VAS NO = 7.6 ± 2.2, VAS smell = 8.6 ± 2.1, NPS = 5.6 ± 1.4, PNIF = 101.6 ± 59.4, S'S = 5.1 ± 3.1), T4 mean values for SNOT-22 = 15.1 ± 12.7, VAS NO = 1.7 ± 1.8, VAS smell = 2.4 ± 3, NPS = 1.7 ± 1.7, PNIF = 162.4 ± 43.2, S'S = 10.4 ± 3.7) (p < 0.0001). No differences in the variables considered were observed between the two age groups during the study, with the exception of the Peak Nasal Inspiratory Flow (PNIF), which was marginally higher; this was also the case according to multivariate analyses (p = 0.008) in the young-middle adult group with respect to the elderly one (p = 0.07). At multivariate analyses, asthma and the female sex negatively influenced the PNIF values (p = 0.001 and p = 0.012, respectively). Age negatively influenced the Visual Analog Scale (VAS) for nasal obstruction (p = 0.0032) and Endoscopic Sinus Surgery (ESS) negatively influenced the patents' olfactory performance (p = 0.028) to the same degree in both groups. Dupilumab was found to be effective to the same degree in both age groups. It can be considered a safe and reliable option for the treatment of elderly patients with severe, uncontrolled CRSwNP.

Switching to Dupilumab from Other Biologics without a Treatment Interval in Patients with Severe Asthma: A Multi-Center Retrospective Study.

Dupilumab is a fully humanized monoclonal antibody that blocks interleukin-4 and interleukin-13 signals. Several large clinical trials have demonstrated the efficacy of dupilumab in patients with severe asthma. However, few studies have examined a switch to dupilumab from other biologics. This retrospective, multi-center observational study was conducted by the Okayama Respiratory Disease Study Group. Consecutive patients with severe asthma who were switched to dupilumab from other biologics without a treatment interval between May 2019 and September 2021 were enrolled. Patients with a treatment interval of more than twice the standard dosing interval for the previous biologic prior to dupilumab administration were excluded. The median patient age of the 27 patients enrolled in this study was 57 years (IQR, 45-68 years). Eosinophilic chronic rhinosinusitis (ECRS)/chronic rhinosinusitis with nasal polyp (CRSwNP) was confirmed in 23 patients. Previous biologics consisted of omalizumab (n = 3), mepolizumab (n = 3), and benralizumab (n = 21). Dupilumab significantly improved FEV1 (median improvement: +145 mL) and the asthma control test score (median improvement: +2). The overall response rate in patients receiving dupilumab for asthma as determined using the Global Evaluations of Treatment Effectiveness (GETE) was 77.8%. There were no significant differences in the baseline characteristics of the GETE-improved group vs. the non-GETE-improved group. ECRS/CRSwNP improved in 20 of the 23 patients (87.0%). Overall, 8 of the 27 patients (29.6%) developed transient hypereosinophilia (>1500/μL), but all were asymptomatic and able to continue dupilumab therapy. Dupilumab was highly effective for the treatment of severe asthma and ECRS/CRSwNP, even in patients switched from other biologics without a treatment interval.

Impact of exacerbation history on long-term efficacy of dupilumab in patients with asthma.

The phase 3 QUEST (NCT02414854) and TRAVERSE (NCT02134028) studies demonstrated the efficacy of dupilumab 200/300 mg versus placebo every 2 weeks for 52 weeks (QUEST) and dupilumab 300 mg up to an additional 96 weeks (TRAVERSE) in patients ≥12 years of age with uncontrolled, moderate-to-severe asthma. Overall, safety was consistent with the known dupilumab safety profile. This post hoc analysis assessed long-term dupilumab efficacy for up to 3 years by exacerbation history. Unadjusted annualised severe exacerbation rates (AER) and change from parent study baseline (PSBL) in pre-bronchodilator forced expiratory volume in 1 s (FEV1) and 5-item Asthma Control Questionnaire (ACQ-5) score were assessed in patients with PSBL eosinophils ≥150 cells·µL-1 or fractional exhaled nitric oxide ≥20 ppb and 1 (n=624), 2 (n=344), or ≥3 (n=311) exacerbations in the year before enrolment in QUEST. In all three groups, dupilumab treatment progressively reduced AER range to 0.17-0.30 during TRAVERSE (Weeks 48-96), increased pre-bronchodilator FEV1 range by 0.28-0.49 L by Week 96 and improved asthma control (reduced ACQ-5 score range by 1.51-2.03 by Week 48). For patients who first received dupilumab upon TRAVERSE enrolment, AER decreased, and lung function and asthma control improved rapidly, as was observed upon initiation of dupilumab in QUEST. Dupilumab was efficacious regardless of exacerbation history. For patients with uncontrolled, moderate-to-severe asthma with elevation of at least one type 2 biomarker, dupilumab treatment provides sustained, long-term reduction of exacerbation rates and improvements in lung function and asthma control irrespective of exacerbation history.

Efficacy and safety profile of dupilumab for the treatment of atopic dermatitis in children and adolescents: A systematic review and meta-analysis.

Dupilumab is the first biologic approved for the treatment of moderate-to-severe atopic dermatitis (AD) in children and adolescents. Previous systematic reviews explored the effectiveness and safety of dupilumab in adults with AD. However, the underlying mechanisms of AD can vary among different age groups, emphasizing the need for separate investigation into the use of dupilumab in children and adolescents with AD. To evaluate the efficacy and safety of dupilumab in children and adolescents with AD based on evidence from clinical trials and observational studies. The process of meta-analysis was conducted according to preferred reporting items for systematic reviews and meta-analyses guidelines. Seven clinical trials and 11 observational studies involving 1275 children and adolescents with AD were eligible for quantitative analysis. Overall, the pooled percentages of eczema area and severity index (EASI) 50, EASI 75, EASI 90, EASI 100, and investigator's global assessment (IGA) 0/1 were 72.9% (95% CI: 61.6%-81.9%), 57.4% (48.1%-66.2%), 31.3% (24.0%-39.7%), 29.7% (23.3%-37.0%), and 35.2% (29.3%-41.5%). With prolonged treatment time, an increase was seen in the pooled rate of EASI response, indicating that dupilumab may provide sustained benefits for children and adolescents over the long term. The reported adverse events were primarily mild and manageable, with an overall incidence rate of 7.2% across clinical trials and 7.6% across observational studies. Dupilumab was an effective and safe treatment option for children and adolescents with AD, with positive results observed from long-term use and an acceptable safety profile. More long-term, high-quality, controlled studies in different regions are needed for further verification.

Evaluation of Dupilumab in Patients With Bullous Pemphigoid

Dupilumab is a theoretically novel therapy for bullous pemphigoid (BP). However, its effectiveness and safety have yet to be confirmed in a large-scale study. To assess the efficacy and safety of dupilumab in patients with BP and evaluate factors that potentially affect short-term and long-term outcomes. A retrospective cohort study was conducted from January 1, 2021, to July 31, 2022. The median (IQR) follow-up period was 24.6 (11.5-38.4) weeks. This multicenter study was performed in 6 dermatology departments of the National Autoimmune Bullous Diseases Cooperative Group of China. Adult patients with BP that received 300 mg of dupilumab every 2 weeks following an initial dose of 600 mg were included. Patients were eligible if they had a clinical presentation of BP combined with immunological or pathological evidence. Patients with drug-induced BP, with less than 4 weeks of follow-up, and who received dupilumab or any other biologics within 6 months were excluded. The primary outcome was the proportion of patients who achieved disease control within 4 weeks. Disease control was defined as the absence of new lesions and pruritus, combined with the healing of existing lesions. Complete remission rates, relapse rates, changes in Bullous Pemphigoid Disease Area Index (BPDAI) scores, itching numerical rating scale (NRS) scores, laboratory results within 64 weeks, and adverse events (AEs) were also assessed. Among 146 patients (median [IQR] age, 73 [64-85] years; 86 [58.9%] male patients) included in the study, 127 (87.0%) patients achieved disease control within 4 weeks, with a median (IQR) time of 14 (7-14) days. A total of 52 (35.6%) patients achieved complete remission, and 13 (8.9%) patients relapsed during the observation period. The complete remission rate and cumulative relapse rate at week 64 were 62.5% (5 of 8) and 30.9%, respectively. There was rapid and sustained improvement in clinical indicators and laboratory examination results after dupilumab treatment, including BPDAI scores, itching NRS scores, serum anti-BP180 and anti-BP230 antibodies, total IgE levels, and eosinophil count. Of these 146 patients, 107 (73.3%) did not report any AEs. The most common AEs were infections and eosinophilia. Serum anti-BP180 antibody levels of greater than 50 relative units (RU)/mL (OR, 3.63; 95% CI, 0.97-12.61; P = .045) were associated with 4-week disease control, and male patients were more likely to relapse (HR, 10.97; 95% CI, 1.42-84.92; P = .02). In this retrospective cohort study, dupilumab treatment was associated with improved clinical symptoms in patients with BP. The safety profile was favorable, although concurrent infection and eosinophilia might pose potential concerns. This study suggests that patients with anti-BP180 antibody levels of at least 50 RU/mL and female sex may respond better.

Severe chronic rhinosinusitis treated with dupilumab, a real-life analysis of early effectiveness.

The present study evaluated the safety and efficacy of dupilumab in severe uncontrolled type 2 chronic rhinosinusitis with nasal polyps (CRSwNP). A retrospective analysis was conducted on a cohort of adult patients affected by severe CRSwNP treated with dupilumab. Maxillofacial computed tomography, evaluation of blood eosinophils and serum IgE levels, measurement of nasal polyp score (NPS), smell identification test (SSIT-16), sinonasal outcome test-22 (SNOT-22) and asthma control test (ACT) were performed. Follow-up was conducted at 2 weeks, and at 1, 3, and 6 months. Adverse events and the efficacy of treatment were monitored. 23 patients were enrolled. After 15 days, scores of the SNOT-22, NPS and SSIT-16 significantly improved. These outcomes were also maintained after 1, 3, and 6 months (p < 0.001). At this latter follow-up time, SNOT-22 showed a change of -33.10 (p < 0.001), NPS -3.36 (p < 0.001) and SSIT-16 +5.60 (p < 0.001). In all, 26.1% of patients experienced early minor complications. In the present study, dupilumab was effective in the treatment of severe uncontrolled CRSwNP, demonstrating a quick significant improvement in both questionnaires and endoscopic evaluation. Only minor complications were observed.

Dupilumab for cancer-associated refractory pruritus.

Pruritus can be an intolerable symptom in patients with cancer. Type 2 inflammation, and specifically, the cytokines IL-4, IL-13, and IL-31, play major roles in the itching process. Dupilumab is an antibody against IL-4Rα, which is a common IL-4 and IL-13 receptor subunit. Blocking IL-4 and IL-13 activity reduces the synthesis of IL-31, the "itch cytokine," and receptors for these 3 cytokines are expressed on itch nerves. Dupilumab is approved for treating moderate-to-severe atopic dermatitis, of which itching is a significant symptom. The objective of this case study was to present the initial evidence of the safety and efficacy of dupilumab as a treatment for intractable malignancy-associated pruritus in 3 patients, thereby providing a basis for further investigation in a larger cohort. As a proof of concept, we used dupilumab in our center to treat 3 patients with intractable malignancy-associated pruritus. The first patient was a 73-year-old male with a history of prostate cancer, the second patient was a 75-year-old female with cutaneous T-cell lymphoma, and the third patient was a 32-year-old male with metastatic melanoma. All 3 patients experienced debilitating itching, which started at some stage after the malignancy had been diagnosed. Moreover, none of the 3 patients showed clinical evidence of atopic dermatitis or other causes of itching (eg, uremia or liver failure), and none of the 3 patients responded to conventional treatments for pruritus. Biweekly treatment with dupilumab led to an immediate improvement in itching, which subsided entirely after a few doses without any significant adverse effects. We propose that dupilumab is a safe and effective treatment for intractable malignancy-associated pruritus, and we are currently testing it in a large cohort.

Dupilumab sustains efficacy in patients with moderate-to-severe type 2 asthma regardless of ICS dose.

Dupilumab, a human monoclonal antibody, blocks the shared receptor component for interleukins-4/13, key and central drivers of type 2 inflammation. The TRAVERSE (NCT02134028) open-label extension study demonstrated the long-term safety and efficacy of dupilumab in patients ≥12 years who completed a previous dupilumab asthma study. The safety profile was consistent with that observed in the parent studies. Here, we assess whether dupilumab sustains long-term efficacy in patients regardless of inhaled corticosteroid (ICS) dose at parent study baseline (PSBL). Patients from phase 2b (NCT01854047) or phase 3 (QUEST; NCT02414854) studies receiving high- or medium-dose ICS at PSBL and enrolled in TRAVERSE were included. We analyzed unadjusted annualized severe exacerbation rates, change from PSBL in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1 ), 5-item asthma control questionnaire, and type 2 biomarkers in patients with type 2 asthma at baseline (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide [FeNO] ≥25 ppb), and subgroups defined by baseline blood eosinophils or FeNO. Of patients with type 2 asthma (n = 1666), 891 (53.5%) were receiving high-dose ICS at PSBL. In this subgroup, unadjusted exacerbation rates for dupilumab versus placebo were 0.517 versus 1.883 (phase 2b) and 0.571 versus 1.300 (QUEST) over the parent study (52 weeks) and remained low throughout TRAVERSE (0.313-0.494). Improvements in pre-BD FEV1 were sustained throughout TRAVERSE. Similar clinical efficacy was observed among patients receiving medium-dose ICS at PSBL and biomarker subgroups. Dupilumab showed sustained efficacy for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 asthma on high- or medium-dose ICS.

The relationship of sinus opacification, olfaction and dupilumab efficacy in patients with CRSwNP.

Loss of sense of smell is one of the most burdensome symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP) but its relationship to sinus disease on imaging is unclear. Dupilumab improves sense of smell and radiographic severity of sinus disease in patients with CRSwNP. We investigated the relationship of sinus opacification severity and loci to olfactory impairment and dupilumab efficacy in patients with CRSwNP from the SINUS-24/SINUS-52 (NCT02912468/NCT02898454) studies. Sinus opacification was evaluated using the Lund-Mackay computed tomography (LMK-CT) score and sense of smell using patient-reported loss of smell (LoS) score, University of Pennsylvania Smell Identification Test (UPSIT) score and the 22-item Sino-Nasal Outcome Test (SNOT-22) smell/taste item. At baseline, 95% of patients (688/724) had impaired sense of smell and opacification was extensive across all sinuses. Greater olfactory impairment was associated with greater opacification, especially in the ethmoid, sphenoid and frontal sinuses. At Week 24, reductions in LMK-CT total score and ethmoid and sphenoid sinus scores with dupilumab were weakly correlated with improvements in sense of smell assessed by LoS, UPSIT and SNOT-22 smell/taste item. More dupilumab than placebo patients achieved clinically meaningful improvement in LMK-CT total score at Week 24 and Week 52. Radiographic disease severity on imaging was associated with smell outcomes in this cohort. Opacification of the ethmoid, sphenoid and frontal sinuses was associated with severe smell loss. These data suggest that dupilumab effects on smell may be partly mediated through reduced sinus inflammation.

PD06 Efficacy of dupilumab in chronic actinic dermatitis

Abstract Chronic actinic dermatitis (CAD) is characterized by a photoexposed site dermatitis in association with objective evidence of photosensitivity, often arising on a background of atopic dermatitis (AD). Dupilumab is a monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13 and is licensed for the management of moderate-to-severe AD. To date, nine case reports have suggested that dupilumab can be clinically effective for CAD, yet only five cases had diagnostic baseline phototesting and only two cases could demonstrate objective improvement in photosensitivity on repeat testing. We report a retrospective case series from two UK photobiology units of 11 patients with concomitant AD and CAD treated with dupilumab. Inclusion criteria included baseline phototesting with an irradiation monochromator device confirming a diagnosis of CAD &amp;lt; 3 years prior to starting dupilumab, phototesting repeated after at least 16 weeks on dupilumab and all patients included were refractory or intolerant to at least one other systemic therapy prior to dupilumab. Eleven patients [82% male, median age 40 years (range 21–59) at diagnosis] of skin phototypes I–V were included. All patients had a pre-existing diagnosis of AD before the onset of CAD, and two patients also had a pre-existing diagnosis of allergic contact dermatitis. The average duration of dupilumab therapy prior to repeat phototesting was 15 months (range 4–44). Ten of 11 (91%) patients reported improvement in their AD in terms of both rash and pruritus. Five of 11 patients (45%) reported partial improvement in their subjective photosensitivity of whom two showed ultraviolet B monochromator improvement (3- to 6-fold). Six of 11 (55%) patients reported no clinical change in photosensitivity of whom two showed no improvement or worsening on phototesting; while four showed improvements, they remained in the severely photosensitive range on phototesting. While dupilumab is an effective therapy for moderate-to-severe AD, its potential benefit in managing CAD is more difficult to measure. In 91% of patients with CAD, dupilumab was associated with improvement in AD, while clinical or objective improvement in photosensitivity occurred in 82%, albeit sometimes only to a slight degree. However, these data suggest that, for patients with CAD and concomitant AD, reducing the eczematous response is beneficial and that dupilumab is a treatment worth exploring for this patient cohort for whom other treatment options are limited. Prospective studies of dupilumab in CAD are required to further evaluate its utility in this therapeutically challenging condition.