Dupilumab Group Research Articles

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.

Ocular Surface Disease in Patients With Atopic Dermatitis Treated With Dupilumab: A Prospective Case-Control Study.

The aim of this study was to evaluate the variation of dry eye disease (DED) prevalence in patients with atopic dermatitis (AD) treated with dupilumab. This prospective case-control study included consecutive patients with moderate-to-severe AD scheduled for dupilumab between May and December 2021 and healthy subjects. DED prevalence, the Ocular Surface Disease Index, tear film breakup time test, osmolarity, Oxford staining score, and Schirmer test results were collected at baseline, 1 month, and 6 months after dupilumab therapy. The Eczema Area and Severity Index was assessed at baseline. Ocular side effects and discontinuation of dupilumab were also recorded. Seventy-two eyes from 36 patients with AD treated with dupilumab and 36 healthy controls were included. Prevalence of DED increased from 16.7% at baseline to 33.3% at 6 months in the dupilumab group ( P = 0.001), whereas it remained unchanged in the control group ( P = 0.110). At 6 months, the Ocular Surface Disease Index and Oxford score increased (from 8.5 ± 9.8 to 11.0 ± 13.0, P = 0.068, and from 0.1 ± 0.5 to 0.3 ± 0.6, P = 0.050, respectively), the tear film breakup time test and Schirmer test results decreased (from 7.8 ± 2.6 s to 7.1 ± 2.7 s, P < 0.001, and from 15.4 ± 9.6 mm to 13.2 ± 7.9 mm, P = 0.036, respectively) in the dupilumab group, whereas they remained stable in the control group ( P > 0.05). Osmolarity was unchanged (dupilumab P = 0.987 and controls P = 0.073). At 6 months after dupilumab therapy, 42% of patients had conjunctivitis, 36% blepharitis, and 2.8% keratitis. No severe side effects were reported, and none of the patients discontinued dupilumab. No association between Eczema Area and Severity Index and DED prevalence was shown. DED prevalence increased in patients with AD treated with dupilumab at 6 months. However, no severe ocular side effects were found and no patient discontinued therapy.

P73 Laboratory safety from a 16-week phase III study of dupilumab in patients aged 6 months–5 years with moderate-to-severe atopic dermatitis

Abstract Previous studies of dupilumab treatment in adults, adolescents and children aged 6–11 years with moderate-to-severe atopic dermatitis (AD) showed no clinically meaningful changes in laboratory parameters. Here, we evaluate laboratory safety data for dupilumab-treated children aged 6 months–5 years with moderate-to-severe AD. In LIBERTY AD PRESCHOOL (NCT03346434 part B), a placebo-controlled phase III trial, 162 children aged 6 months–5 years with moderate-to-severe AD were randomized to receive dupilumab 200 mg or 300 mg every 4 weeks (n = 83) based on baseline weight (200 mg: ≥ 5 to &amp;lt; 15 kg; 300 mg: ≥ 15 to &amp;lt; 30 kg), or placebo (n = 79) for 16 weeks. Low-potency topical corticosteroids were initiated from day −14. At baseline, mean (SD) haematology parameters were similar in both treatment groups: eosinophils [dupilumab: 1.1 × 109 cells L−1 (0.7); placebo: 1.1 × 109 cells L−1 (0.7)], platelets [dupilumab: 397.7 × 109 cells L−1 (103.2), placebo: 385.6 × 109 cells L−1 (112.9)] and neutrophils [dupilumab: 3.54 × 109 cells L−1 (1.56); placebo: 3.85 × 109 cells L−1 (1.73)]. Mean (SD) counts of neutrophils [dupilumab: 3.18 × 109 cells L−1 (1.94); placebo: 3.79 × 109 cells L−1 (1.91)] remained within the normal reference interval (RI) at week 16. Mean (SD) change in platelet count at week 16 was −16.3 × 109 cells L−1 (78.5) in the dupilumab group and 17.4 × 109 cells L−1 (106.6) in the placebo group. In the dupilumab group, the mean (SD) change in eosinophil count increased at week 4 [0.48 × 109 cells L−1 (1.8)] and trended downward by week 16 [0.31 × 109 cells L−1 (1.4)], while minimal changes were noted in the placebo group at week 4 [0.1 × 109 cells L−1 (0.7)] and week 16 [−0.2 × 109 cells L−1 (0.7)]. The mean (SD) values for creatine kinase [dupilumab: 144.2 U L−1 (84.8); placebo: 130.7 U L−1 (46.39)], alkaline phosphatase [dupilumab: 273.4 U L−1 (80.01); placebo: 233.2 U L−1 (65.98)] and lactate dehydrogenase [dupilumab: 283.8 U L−1 (44.74); placebo: 317.4 U L−1 (67.58)] at week 16 remained within the normal RI in all treatment groups. Two patients treated with dupilumab reported cases of severe and moderate eosinophilia. Neither event was associated with clinical symptoms nor led to the discontinuation of study treatment. No clinically meaningful changes in haematology or chemistry laboratory safety parameters in children aged 6 months–5 years with moderate-to-severe AD were seen with 16 weeks of dupilumab treatment. These data demonstrate that, as with adults, adolescents and older children, routine laboratory monitoring is unnecessary in this population. Funding sources: research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.

Effect of abrocitinib and dupilumab on eosinophil levels in patients with moderate‐to‐severe atopic dermatitis

AbstractBackgroundEosinophilia is common in patients with atopic dermatitis (AD). Abrocitinib, an oral Janus kinase‐1 inhibitor and dupilumab, an anti–interleukin‐4 receptor‐α antibody, are approved for moderate‐to‐severe AD. Dupilumab has been associated with transient eosinophilia.ObjectivesTo assess the effect of abrocitinib and dupilumab on eosinophils in patients from the phase 3 JADE COMPARE (NCT03720470) and JADE EXTEND (NCT03422822) trials.MethodsIn JADE COMPARE, patients received once‐daily oral abrocitinib (200/100 mg), placebo or subcutaneous dupilumab (300 mg, biweekly) with background topical therapy. In the ongoing long‐term JADE EXTEND study (Data cutoff: April 22, 2020), dupilumab‐treated patients from JADE COMPARE received once‐daily abrocitinib (200/100 mg) with background topical therapy. The proportion of patients with eosinophilia and hypereosinophilia, and association of eosinophilia with clinical efficacy was assessed. Adverse events (AEs) were also assessed.ResultsOf the 837 patients in JADE COMPARE, 58 (25.7%), 47 (19.7%) and 51 (21.1%) had eosinophilia at baseline in the abrocitinib 200 mg, abrocitinib 100 mg and dupilumab groups, respectively. At Week 16, eosinophilia decreased with abrocitinib 200 mg (9.3%) and abrocitinib 100 mg (19.0%) but not dupilumab (21.5%); no cases of hypereosinophilia were observed with abrocitinib 200 mg compared with abrocitinib 100 mg (1.9%) and dupilumab (2.3%). Decreases in median eosinophil counts were greater with abrocitinib 200 mg (difference, −100/mm3) and abrocitinib 100 mg (−70/mm3) than dupilumab (+25/mm3) or placebo (+30/mm3) at Week 16. Similar trends were observed in patients with comorbid asthma and allergic rhinitis. Eosinophilia decreased from baseline to Week 12 in dupilumab‐treated patients who switched to abrocitinib in JADE EXTEND. Decreased eosinophil counts with abrocitinib correlated positively with improvements in AD severity, itch and sleep loss. No eosinophilia‐associated AEs occurred.ConclusionsAbrocitinib decreased eosinophilia in patients with moderate‐to‐severe AD who had baseline eosinophilia. Resolution of eosinophilia was associated with abrocitinib clinical efficacy.

WITHDRAWN: Prospective direct comparison of biological treatments on severe eosinophilic asthma: Findings from the PRISM study

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Comparison of Efficacy of Baricitinib and Dupilumab in the Treatment of Chinese Moderate-To-Severe Atopic Dermatitis: A Retrospective Study

Introduction: The treatment of atopic dermatitis (AD) patients with insufficient response or intolerance to topical medication remains clinical challenges, and there is a paucity of head-to-head trials comparing the efficacy of novel biological agents such as JAK inhibitor and antibody. Methods: To compare the efficacy of selective JAK1/JAK2 inhibitor baricitinib and interleukin-4 monoclonal antibody dupilumab in the treatment of patients with moderate-to-severe AD, a retrospective cohort study method was adopted. Clinical data from June 2020 to April 2022 were systematically reviewed. Eligible patients who received baricitinib or dupilumab were screened according to the following inclusion criteria: (1) age ≥ 18 years; (2) moderate-to-severe AD: baseline investigator global assessment (IGA) score ≥ 3, baseline eczema area and severity index (EASI) score ≥ 16; (3) poor response or intolerance to at least one topical drug in the past 6 months; (4) no topical glucocorticoids were used in the past 2 weeks and no systematic treatment was given in the past 4 weeks. Patients of the baricitinib group were treated with oral baricitinib in doses of 2 mg per day for 16 weeks, and patients of the dupilumab group were treated with standardized use of dupilumab for 16 weeks, with the initial 600 mg subcutaneous injection and the following 300 mg subcutaneous injection every 2 weeks. The clinical efficacy score indexes including the IGA score, EASI score, and Itch Numeric Rating Scale (NRS) score. These scores at 0, 2, 4, 8, 12, and 16 weeks after the start of treatment were collected. Results: A total of 54/45 patients treated with baricitinib/dupilumab were included. There was no significant difference in the decrease of all scores between the two groups at the 4th week (p > 0.05). There was no difference in the EASI score and Itch NRS score (p > 0.05), but the IGA score of the baricitinib group was lower at the 16th week (Z = 4.284, p < 0.001). Within the first 4 weeks, the Itch NRS score of the baricitinib group decreased rapidly, but with the prolongation of treatment time, there was no significant difference between the two groups at the 16th week (Z = 1.721, p = 0.085). Conclusions: The efficacy of baricitinib at a dose of 2 mg daily was similar to dupilumab, and the improvement in pruritus was significantly faster in the early stage of treatment (the first 4 weeks) than that of dupilumab.

Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts

BackgroundIn some patients with chronic obstructive pulmonary disease (COPD), type 2 inflammation may increase exacerbation risk and may be indicated by elevated blood eosinophil counts. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation.MethodsIn a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of at least 300 per microliter and an elevated exacerbation risk despite the use of standard triple therapy to receive dupilumab (300 mg) or placebo subcutaneously once every 2 weeks. The primary end point was the annualized rate of moderate or severe exacerbations of COPD. Key secondary and other end points that were corrected for multiplicity were the change in the prebronchodilator forced expiratory volume in 1 second (FEV1) and in the scores on the St. George’s Respiratory Questionnaire (SGRQ; range, 0 to 100, with lower scores indicating a better quality of life) and the Evaluating Respiratory Symptoms in COPD (E-RS–COPD; range, 0 to 40, with lower scores indicating less severe symptoms).ResultsA total of 939 patients underwent randomization: 468 to the dupilumab group and 471 to the placebo group. The annualized rate of moderate or severe exacerbations was 0.78 (95% confidence interval [CI], 0.64 to 0.93) with dupilumab and 1.10 (95% CI, 0.93 to 1.30) with placebo (rate ratio, 0.70; 95% CI, 0.58 to 0.86; P<0.001). The prebronchodilator FEV1 increased from baseline to week 12 by a least-squares (LS) mean of 160 ml (95% CI, 126 to 195) with dupilumab and 77 ml (95% CI, 42 to 112) with placebo (LS mean difference, 83 ml; 95% CI, 42 to 125; P<0.001), a difference that was sustained through week 52. At week 52, the SGRQ score had improved by an LS mean of −9.7 (95% CI, −11.3 to −8.1) with dupilumab and −6.4 (95% CI, −8.0 to −4.8) with placebo (LS mean difference, −3.4; 95% CI, −5.5 to −1.3; P=0.002). The E-RS–COPD score at week 52 had improved by an LS mean of −2.7 (95% CI, −3.2 to −2.2) with dupilumab and −1.6 (95% CI, −2.1 to −1.1) with placebo (LS mean difference, −1.1; 95% CI, −1.8 to −0.4; P=0.001). The numbers of patients with adverse events that led to discontinuation of dupilumab or placebo, serious adverse events, and adverse events that led to death were balanced in the two groups.ConclusionsAmong patients with COPD who had type 2 inflammation as indicated by elevated blood eosinophil counts, those who received dupilumab had fewer exacerbations, better lung function and quality of life, and less severe respiratory symptoms than those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; BOREAS ClinicalTrials.gov number, NCT03930732.)

The efficacy and safety of dupilumab combined with methylprednisolone in the treatment of bullous pemphigoid in China.

We access the safety and efficacy of methylprednisolone combined with dupilumab in treating the bullous pemphigoid. 27 patients were enrolled, of which 9 received dupilumab in addition to methylprednisolone (dupilumab group, D group), while the other 18 patients were administered methylprednisolone alone (traditional group, T group). The median time to stop the formation of the new blister was 5.5days (3.5-11.75days) and 10days (9-15days) in the D group and the T group, respectively (p=0.032). Additionally, the median time of complete healing reached was 21days (16.25-31days) and 29days (25-50days) in the D group and the T group, separately (p=0.042). The median amount of cumulative methylprednisolone at the time of disease control was 240mg (140-580mg) and 460mg (400-840mg) in the D group and the T group, respectively (p=0.031). The total amount of the methylprednisolone used at the time of complete healing reached was 792mg (597-1,488.5mg) in the D group while that was 1,370mg (1,000-2,570mg) in the T group (p=0.028). No adverse event associated with dupilumab was recorded. Methylprednisolone in combination with dupilumab appeared superior to methylprednisolone alone in control of disease progression and the methylprednisolone-sparing effect.

Dupilumab improves eosinophilic otitis media associated with eosinophilic chronic rhinosinusitis

BackgroundEosinophilic otitis media (EOM) is a refractory condition associated with eosinophilic chronic rhinosinusitis and bronchial asthma. EOM is characterized by type-2 inflammation and is refractory to various treatments. We investigated the efficacy of dupilumab, interleukin-4 receptor alpha antagonist, for patients with EOM complicated by eosinophilic chronic rhinosinusitis (ECRS). MethodsBetween April 2017 and April 2022, we treated 124 patients with dupilumab for refractory CRS or bronchial asthma. Of these, 14 had EOM concurrently, and 10 of them who had been treated for >6 months were included in our study. We retrospectively evaluated the efficacy of dupilumab by the amount of systemic corticosteroid used, the frequency of exacerbations, severity score of EOM, computed tomography (CT) score of temporal bones, and pure tone audiometry. We also enrolled 8 EOM patients without dupilumab treatment as a control group. ResultsDupilumab significantly improved the amount of systemic corticosteroid used and the frequency of exacerbation and compared with before dupilumab was used (p = 0.01 and <0.01, respectively). All patients could be weaned from systemic-corticosteroid therapy by 54 weeks of dupilumab use. The severity score of EOM and CT score for temporal bones were significantly lower than before the treatment (p = 0.01 and 0.01, respectively). Compared to the control group, the systemic corticosteroid used and severity scores were improved in the dupilumab group (p = 0.02 and < 0.01, respectively). ConclusionsDupilumab could be used to wean patients from systemic corticosteroids with the improvement of severity score in EOM associated with ECRS and bronchial asthma.

Association between Dupilumab and Conjunctivitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Conjunctivitis is commonly reported in dupilumab users with atopic dermatitis (AD), and few studies have compared the risk of conjunctivitis among patients with different indications. This study aimed to investigate the association between dupilumab and conjunctivitis in various diseases. The protocol of this study was registered on PROSPERO (ID CRD42023396204). The electronic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov was conducted for the period from their inception to January 2023. Only placebo-controlled, randomized controlled trials (RCTs) were included. The main outcome was the incidence of conjunctivitis during the study period. The subgroup analysis was performed for patients with AD and non-AD indications, which include asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis. In total, 23 RCTs involving 9153 patients were included for meta-analysis. Dupilumab users exhibited significantly higher risk of conjunctivitis (risk ratio [RR], 1.89; 95% confidence interval [CI], 1.34-2.67) than placebo users. Notably, significantly increased incidence of conjunctivitis was observed in the dupilumab group relative to the placebo group among patients with AD (RR, 2.43; 95% CI, 1.84-3.12) but not among patients with non-AD indications (RR, 0.71; 95% CI, 0.43-1.13). In conclusion, only dupilumab users with AD but not those with non-AD indications reported an elevated incidence of conjunctivitis.

Comparative effectiveness of omalizumab, mepolizumab, and dupilumab in asthma: A target trial emulation

Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness. Our aim was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab in individuals with moderate-to-severe asthma. We emulated a hypothetical randomized trial using electronic health records from a large US-based academic health care system. Participants aged 18 years or older with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/μL were eligible for study inclusion. The study period extended from March 2016 to August 2021. Outcomes included the incidence of asthma-related exacerbations and change in baseline FEV1 value over 12 months of follow-up. In all, 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab met the inclusion criteria. Over 12 months of follow-up, 31 exacerbations occurred over 68 person years (0.46 exacerbations per person year) in the dupilumab group, 63 over 68 person years (0.93 per person year) in the omalizumab group, and 86 over 65 person years (1.32 per person year) in the mepolizumab group (adjusted incidence rate ratios: dupilumab vs mepolizumab, 0.28 [95% CI= 0.09-0.84]; dupilumab vs omalizumab, 0.36 [95% CI= 0.12-1.09]; and omalizumab vs mepolizumab, 0.78 [95% CI = 0.32-1.91]). The differences in the change in FEV1 comparing patients who received the different biologics were as follows: 0.11 L (95% CI= -0.003 to 0.222 L) for dupilumab versus mepolizumab, 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab, and 0.026 L (95% CI -0.083 to 0.140 L) for omalizumab versus mepolizumab. Among patients with asthma and eosinophil counts of at least 150 cells/μL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV1 value than omalizumab and mepolizumab.

335 Improvement in sleep quality, anxiety and depression in adults with moderate-to-severe atopic dermatitis with dupilumab treatment

Abstract Sleep disturbance is considered one of the most prevalent symptoms of atopic dermatitis (AD), and is associated with daytime sleepiness, anxiety and depression. In previous phase 3 trials, dupilumab treatment demonstrated significant improvement in objective AD signs and severity of symptoms, including sleep disturbance and mental health symptoms. To investigate the effect of dupilumab for up to 24 weeks on sleep quality, daytime sleepiness, anxiety and depression, using data from the DUPISTAD (NCT04033367) study. The randomized, phase 4 DUPISTAD study, was divided into two 12-week periods: an initial double-blind placebo-controlled period, and a subsequent 12-week open-label extension (OLE) period. The 24-week study enrolled adult patients with moderate-to-severe AD (Eczema Area and Severity Index score ≥12, Peak Pruritus Numeric Rating Scale [NRS] score ≥3, Sleep Disturbance NRS average score ≥5) who showed an inadequate response to topical treatments. These patients were randomized 2 : 1 to dupilumab 300 mg every 2 weeks (q2w) for both the double-blind and OLE periods or placebo for the initial double-blind period, followed by dupilumab 300 mg q2w for the OLE period. The use of concomitant topical corticosteroids was permitted as needed by both groups throughout the study. Endpoints included mean change from baseline to week 24 for Patient-Reported Outcome Measures Information System (PROMIS) Sleep T-score (standardized score ranging from 30 [best] to 80 [worst], with a mean of 50), Epworth Sleepiness Scale (ESS; scored 0–24; higher values indicate increased daytime sleepiness), and Hospital Anxiety and Depression Scale (HADS; scored 0–21; higher values indicate a worse outcome). Throughout the study, patients also completed a Sleep Diary, recording the NRS of restfulness upon waking up (scored 0–10; lower values indicate a worse outcome). Statistical comparisons were not performed on the data collected during the OLE observation period. A total of 188 patients were enrolled in the study: 127 received continuous dupilumab (dupilumab–dupilumab group) and 61 received placebo to week 12 and then dupilumab to week 24 (placebo–dupilumab group). Baseline demographics and disease characteristics were well balanced. Improvement from baseline in sleep quality, daytime sleepiness, anxiety and depression was observed at week 24 in both groups, as illustrated by the mean change from baseline in PROMIS Sleep T-scores (−12.5 in the dupilumab–dupilumab group and −11.7 in the placebo–dupilumab group), ESS scores (−4.6 in the dupilumab–dupilumab group and −3.7 in the placebo–dupilumab group), HADS anxiety scores (−3.8 in the dupilumab–dupilumab group and −4.4 in the placebo–dupilumab group), HADS depression scores (−4.4 in the dupilumab–dupilumab group and −3.4 in the placebo–dupilumab group), and the NRS of restfulness upon a waking-up item of the Sleep Diary (+3.3 in the dupilumab–dupilumab group and +3.4 in the placebo–dupilumab group). The improvement achieved by the placebo–dupilumab group converged with that of the dupilumab–dupilumab group during the OLE period, as shown by the mean change from week 12 to week 24 in PROMIS Sleep T-score (−3.8), ESS score (−1.9), HADS anxiety score (−1.6), HADS depression score (−0.9) and NRS of restfulness upon a waking-up item of the Sleep Diary (+1.5). The safety profile of dupilumab was consistent with the known safety profile. Dupilumab provided sustained improvement through 24 weeks in patient-reported measures of sleep, daytime sleepiness, anxiety, and depression in adult patients with moderate-to-severe AD. Patients who were switched from placebo to dupilumab at week 12 showed rapid improvement in these parameters after the switch, eventually matching the improvement achieved by patients who received dupilumab from baseline through week 24.

332 Improvement in symptoms of atopic dermatitis (AD) and AD-related quality of life with dupilumab treatment in adults: 24-week results of the DUPISTAD study

Abstract Atopic dermatitis (AD) is a chronic disease characterized by sleep disturbance, associated with night-time itching and scratching, along with skin pain, resulting in daytime drowsiness, diminished daytime productivity and overall reduced quality of life (QoL) in patients with AD. To report the effect of up to 24 weeks of dupilumab treatment on the QoL of adult patients with moderate-to-severe AD, using data from the DUPISTAD (NCT04033367) study. Phase 4, a randomized DUPISTAD study, comprised two 12-week periods: an initial placebo-controlled double-blind period, and a subsequent 12-week open-label extension (OLE) period. Adult patients with moderate-to-severe AD (Eczema Area and Severity Index score ≥12, Peak Pruritus Numeric Rating Scale [NRS] score ≥3, Sleep Disturbance NRS average score ≥5), showing an inadequate response to topical treatments, were randomized 2 : 1 to dupilumab 300 mg every 2 weeks (q2w) for both the double-blind and OLE periods or placebo for the initial double-blind period, followed by dupilumab 300 mg q2w for the OLE period. The use of concomitant topical corticosteroids was permitted during the entire course of the study. Endpoints, including Patient-Oriented Eczema Measure (POEM; scored 0–28, with higher values indicating a worse outcome), Dermatology Life Quality Index (DLQI; scored 0–30, with higher values indicating a poorer QoL), Skin Pain and Sensitivity NRS (scored 0–10, where 0 = no pain/normal sensitivity and 10 = worst possible pain/extremely sensitive) were assessed from baseline to week 24. The enrolled patients also completed a Work Productivity and Activity Impairment Questionnaire (WPAI-AD), including an NRS rating of the AD-Affected Ability to do Regular Daily Activities other than a Job (scored 0–10, where 0=‘no effect’ and 10=‘prevented me from doing my daily activities’). Formal statistical comparisons were not performed on the data resulting from the OLE period. The DUPISTAD study enrolled a total of 188 patients: 127 patients received dupilumab throughout (dupilumab–dupilumab group), and 61 patients received a placebo and then switched to dupilumab (placebo–dupilumab group). Baseline demographics and disease characteristics were well balanced. Improvement from baseline in AD-related patient-reported QoL indicators and AD symptoms was observed at week 24 in both groups, as illustrated by the mean change from baseline in POEM total scores (−14.6 in the dupilumab–dupilumab group and −15.9 in the placebo–dupilumab group), DLQI scores (−12.6 in the dupilumab–dupilumab group and −13.4 in the placebo–dupilumab group), Skin Pain NRS scores (−4.7 in the dupilumab–dupilumab group and −5.0 in the placebo–dupilumab group), Skin Sensitivity NRS scores (−4.6 in the dupilumab–dupilumab group and −5.0 in the placebo–dupilumab group), and the WPAI-AD NRS of Ability to do Regular Daily Activities scores (−4.2 in the dupilumab–dupilumab group and −3.8 in the placebo–dupilumab group). The placebo–dupilumab group experienced most of this improvement during the OLE period, as illustrated by the mean change from week 12 to week 24 in POEM total score (−11.5), DLQI score (−5.5), Skin Pain NRS score (−3.0), Skin Sensitivity NRS score (−3.0) and the WPAI-AD NRS of Ability to do Regular Daily Activities score (−2.0). The safety profile of dupilumab was consistent with the known safety profile. Dupilumab provided sustained improvements through 24 weeks in AD-related patient-reported measures of QoL and AD symptoms in adults with moderate-to-severe AD. Patients who were switched from placebo to dupilumab at week 12 showed rapid improvement in these parameters after the switch, eventually matching the improvement achieved by patients who received dupilumab from baseline through week 24.

329 Efficacy and safety of dupilumab treatment with concomitant topical corticosteroids in children aged 6 months to 5 years with severe atopic dermatitis

Abstract There are limited approved systemic treatment options for children with atopic dermatitis (AD). Dupilumab is now approved in the United States for patients 6 months and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies. European Medicines Agency is evaluating the use of dupilumab in children aged 6 months through 5 years with severe AD only. To report the efficacy and safety of dupilumab in the subgroup of children aged 6 months to 5 years with severe AD (IGA score = 4) at baseline in the LIBERTY AD PRESCHOOL trial (NCT03346434 part B). Patients aged 6 months to 5 years with inadequately controlled moderate-to-severe AD were enrolled in LIBERTY AD PRESCHOOL (part B), a randomized, double-blind placebo-controlled phase 3 study. Patients were randomized to either dupilumab 200/300 mg every 4 weeks (200 mg if baseline weight 5 to &amp;lt;15 kg, 300 mg if 15 to &amp;lt;30 kg) or placebo for 16 weeks. All patients initiated standardized treatment with low-potency topical corticosteroids (TCS) from day –14. This analysis reports efficacy and quality-of-life endpoints including a 75% reduction from baseline in the Eczema Area and Severity Index (EASI-75), Peak-Pruritus Numerical Rating Scale (PP-NRS), Children’s Dermatology Life Quality Index (CDLQI, for children aged 4 to &amp;lt;6 years), and Infant’s Dermatitis Quality Of Life (IDQOL, for children &amp;lt;4 years) in children with severe AD. Of the total trial population of 162 patients with moderate-to-severe AD, 125 patients with severe AD at baseline were randomized: 63 to the dupilumab + TCS treatment group and 62 to the placebo + TCS treatment group. Baseline demographics were similar. Mean (SD) baseline disease characteristics were also similar between the dupilumab and placebo groups: EASI (38.8 [13.7] vs. 35.4 [12]), body surface area (63.1% [21] vs. 58.9% [21.4]), weekly average PP-NRS (7.6 [1.4] vs. 7.6 [1.6]), CDLQI (17.5 [5.5] vs. 17.8 [6.4]) and IDQOL (18.4 [5.1] vs. 17.4 [5.4]). Dupilumab treatment resulted in a rapid and significant increase in the proportion of patients achieving EASI-75 compared with placebo treatment by week 4 (27% vs. 4.8%; P = 0.0009). By week 16, this improvement was further increased compared with the placebo group (46% vs. 7%; P &amp;lt; 0.0001). At week 16, dupilumab-treated patients had a significantly greater percent reduction from baseline in PP-NRS compared with the placebo group (LS mean (SE)–41.8 [5.4] vs. 0.5 [5.4]; P &amp;lt; 0.0001). Dupilumab also resulted in significant improvement in quality-of-life outcomes compared with placebo (LS mean [SE]) change from baseline to week 16 in CDLQI (−9.1 [1.1] vs. −2.6 [1.2]; P &amp;lt; 0.0001); IDQOL (−9.1 [1.3] vs. −0.6 [1.1]; P &amp;lt; 0.0001). Treatment-emergent adverse events (TEAEs) were reported in 42 (66.7%) patients in the dupilumab group and 45 (73.8%) patients in the placebo group. Most TEAEs were mild to moderate and deemed unrelated to the study drug by the investigator. The most common TEAE was atopic dermatitis in both the dupilumab group (10 [15.9%]) and placebo group (16 [26.2%]). Additionally, TEAEs in the conjunctivitis cluster were reported by 4 (6.4%) patients in the dupilumab group and none in the placebo group. In the placebo group, 3 (4.9%) serious adverse events were reported. No dupilumab-related adverse events were serious or led to treatment discontinuation. Dupilumab significantly improved AD signs, symptoms, and quality of life in children aged 6 months to 5 years with severe AD. The safety profile was consistent with that previously seen in adults, adolescents, and children aged &amp;gt; 6 years of age.

344 Dupilumab significantly improves itch and skin lesions in patients with prurigo nodularis: pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Abstract Prurigo nodularis (PN), a chronic inflammatory and pruritic skin condition with severely itchy skin nodules, substantially affects the quality of life and is often inadequately controlled with topical medications. Recently, the US Food and Drug Administration approved dupilumab as the first systemic therapy for PN. Two randomized clinical trials with similar designs, LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679), demonstrated the efficacy and safety of dupilumab in adults with PN inadequately controlled with topical medications or for whom those who were inadvisable. To report the efficacy of dupilumab on pruritus and skin lesions in PN, as well as its safety, by analysing pooled data from PRIME and PRIME2 trials, given their similar trial design. PRIME and PRIME2 were multicentre, randomized, placebo-controlled, double-blinded, phase 3 trials, which comprised a 2–4-week screening, 24-week treatment and 12-week follow-up period. Itch severity was measured by Worst Itch Numerical Rating Scale (WI-NRS), ranging from 0 (no itch) to 10 (worst itch imaginable). The severity of skin lesions was assessed using Investigator’s Global Assessment for PN-Stage (IGA PN-S), as score 0 (no nodules), 1 (1–5 nodules), 2 (6–19 nodules), 3 (20–99 nodules) or 4 (over 100 nodules). To be eligible for enrolment patients had WI-NRS ≥7, and IGA PN-S score of 3 or 4. Patients received subcutaneous dupilumab 300 mg (loading dose, 600 mg) or matched placebo every 2 weeks for 24 weeks. Efficacy endpoints were the proportion of patients with a WI-NRS score reduction of ≥4 points, the proportion of patients who achieved an IGA PN-S score of 0 or 1, and the proportion of patients who achieved concomitantly WI-NRS reduction of ≥4 points and IGA PN-S score of 0 or 1, at week 12 and at week 24. At baseline, demographic and disease characteristics were balanced between the PRIME and PRIME2 pooled dupilumab (n = 153), and pooled placebo groups (n = 158). All but 1 patient had used prior topical medications for PN, and 66.2% had used off-label systemic medications. Despite prior therapies, at baseline, the overall mean (standard deviation) WI-NRS score was 8.5 (1.0); 66.3% of patients had 20–99 nodules, and 33.7% had over 100 nodules. At week 12, the ≥4-point reduction in WI-NRS in the dupilumab group was achieved by 62 patients (40.5%), and at week 24, by 90 (58.8%), compared with 30 patients (19.0%) in the placebo group at each time point (P &amp;lt; 0.0001 for both). An IGA PN-S score of 0 or 1 was achieved by 44 (28.8%) patients in the dupilumab group vs. 19 (12.0%) in the placebo group at week 12 (P = 0.0002), and, respectively, by 71 (46.4%) vs. 27 (17.1%) patients at week 24 (P &amp;lt; 0.0001). The concomitant reduction in WI-NRS by ≥4 points and IGA PN-S score of 0 or 1 was achieved by 28 (18.3%) patients in the dupilumab group vs. 11 (7.0%) in the placebo group at week 12 (P = 0.0021), and, respectively, by 54 (35.3%) vs. 14 (8.9%) patients at week 24 (P &amp;lt; 0.0001). The rate of treatment-emergent adverse events was 59.9% with dupilumab and 51.0% with placebo. The most common adverse events were headache (5.3% vs. 5.7%), neurodermatitis (2.0% vs. 5.7%), skin infections (3.9% vs. 7.6%) and injection-site reactions (3.9% vs. 5.7%) in dupilumab vs. placebo groups. Dupilumab demonstrated clinically meaningful and statistically significant improvements in itch and skin lesions vs. placebo in patients with PN, confirming the findings from individual PRIME and PRIME2 studies. The safety profile of dupilumab was consistent with the known safety profile in its approved indications.

337 Dupilumab treatment is not associated with an increased overall risk of infections in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis

Abstract Patients with atopic dermatitis (AD) have an increased risk of infection, including skin infections. Previous studies in children aged 6–11 years and adolescents showed that dupilumab is not associated with an increased risk of overall infections and is associated with a lower incidence of skin infections compared with a placebo. This post-hoc analysis reports the impact of dupilumab treatment on infections, including skin infections, in children aged 6 months to 5 years with moderate-to-severe AD. In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled trial (NCT03346434, part B), children aged 6 months to 5 years with moderate-to-severe AD (Investigator’s Global Assessment score ≥3) were randomized 1 : 1 to subcutaneous dupilumab every 4 weeks (200 mg if baseline weight was ≥5 to &amp;lt;15 kg, 300 mg if weight was ≥15 to &amp;lt;30 kg) or placebo with concomitant low-potency topical corticosteroids for 16 weeks. Exposure-adjusted rates (patients with ≥1 event per 100 patient-years [nP/100 PY]) and systemic anti-infective medication use (nP/100PY) were used to compare treatment groups. 162 patients were randomized to dupilumab (n = 83) or placebo (n = 79). During the 16-week treatment period, total infections rates were numerically lower in the dupilumab-treated group (nP/100PY: 185.2) compared with the placebo-treated group (nP/100PY: 245.7). Fewer infections of skin-structure and soft tissues were reported in the dupilumab group (nP/100PY: 24.7) compared with the placebo group (nP/100PY: 40.2). Dupilumab-treated patients had significantly lower rates of non-herpetic skin infections (nP/100PY: 42.7) than placebo-treated patients (nP/100PY: 92.7; P &amp;lt; 0.05 vs. placebo). There was no significant difference in rates of herpetic skin infections between the dupilumab (nP/100PY: 20.0) and placebo groups (nP/100PY: 17.1; P = 0.817 vs. placebo). No helminthic infections were reported in either group. Systemic anti-infective medication use was significantly less frequent in the dupilumab group (nP/100PY: 104.7) compared with placebo (nP/100PY: 203.0; P &amp;lt; 0.05 vs. placebo). The overall safety of dupilumab was consistent with the known safety profile. Dupilumab treatment is associated with lower overall infections and significantly lower non-herpetic skin infections than placebo in children aged 6 months to 5 years with moderate-to-severe AD.

336 Efficacy of dupilumab in infants and preschoolers with atopic dermatitis up to 1 year

Abstract Continuous use of several traditional systemic atopic dermatitis (AD) treatments in pediatric patients is not recommended due to safety concerns and lack of long-term efficacy data. Children aged 6 months to 5 years with moderate-to-severe AD who had participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434, part B; parent study) were enrolled in an open-label extension (OLE) study (NCT02612454). Patients received subcutaneous dupilumab every 4 weeks (200 mg for children weighing 5 to &amp;lt;15 kg; 300 mg for 15 to &amp;lt;30 kg). Topical AD treatments were allowed. Relative to the parent study baseline, mean percentage changes (± standard error) in Eczema Area and Severity Index score were −41.6 (±4.6) and −54.0 (±3.2) at OLE baseline, −74.5 (±3.7) and −81.7 (±1.8) at week 16, and −85.6 (±3.5) and −86.4 (±2.2) at week 52 in the 200 and 300 mg dupilumab groups, respectively. The number of patients (%) achieving an Investigator’s Global Assessment score of 0/1 increased from OLE baseline (6/61 [9.8%] and 15/116 [12.9%]) to week 16 (22/58 [37.9%] and 35/115 [30.4%]), and at week 52 (16/34 [47.1%] and 18/54 [33.3%]) in the 200 and 300 mg dupilumab groups, respectively. The overall safety of dupilumab treatment administered for up to 1 year was consistent with the known dupilumab safety profile. Dupilumab treatment for 1 year provides sustained improvement in signs of AD in patients aged 6 months to 5 years with moderate-to-severe AD.

343 Dupilumab efficacy on itch and skin lesions in adult patients with prurigo nodularis may be observed concurrently or independently over 24 weeks: results from two phase 3 trials

Abstract Prurigo nodularis (PN) is a chronic inflammatory and pruritic skin disease. Clinically it is characterized by intense pruritus accompanied by hyperkeratotic nodules often associated with a very low quality of life including sleep disruption. The FDA has recently approved dupilumab as the only treatment for PN, but it is unknown to what extent within-patient categorical improvements in itch and skin lesions occurred concurrently or independently. Two phase 3 clinical trials, LIBERTY-PN PRIME and PRIME2, demonstrated dupilumab efficacy and safety in patients with PN. To report the efficacy of dupilumab on signs and symptoms in adult patients with PN who did and did not achieve the multicomponent endpoint. LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679) were randomized, double-blind, placebo-controlled, multicentre, parallel-group, phase 3 trials in adult patients with PN with ≥20 PN lesions and severe itch, inadequately controlled with topical prescription therapies or for whom these are inadvisable. Here, data were pooled from the two studies. Patients received 300 mg dupilumab subcutaneously (600 mg loading dose; n = 153) or matched placebo (n = 158) every 2 weeks for 24 weeks. This abstract assesses efficacy in patients who did and those who did not achieve the stringent multicomponent endpoint of ≥4-point improvement from baseline in Worst Itch Numerical Rating Scale (WI-NRS, range: 0–10) and Investigator’s Global Assessment PN Stage (IGA PN-S, score range: 0–4) score 0 or 1 (clear or almost clear; defined as 5 or fewer nodules) at week 24. Endpoints include a proportion of patients with concomitant ≥4-point reduction in WI-NRS from baseline and IGA PN-S score 0 or 1 at week 24; the proportion of patients with ≥4-point reduction in WI-NRS from baseline or IGA PN-S score 0 or 1 at week 24; and proportion of patients not achieving ≥4-point reduction in WI-NRS from baseline and IGA PN-S score 0 or 1 at week 24. Safety was also assessed. Baseline demographic and clinical characteristics were generally balanced between subgroups. The proportion of patients treated with dupilumab and placebo who achieved the multicomponent endpoints was 35.3% and 8.9%, respectively; and who achieved WI-NRS reduction of ≥4 points from baseline or IGA PN-S score 0 or 1 at week 24 was 69.9% and 27.2%, respectively. Among multicomponent nonresponders in the dupilumab group (n = 99), 36.4% achieved WI-NRS reduction of ≥4 points and 17.2% achieved IGA PN-S score 0 or 1; in the placebo group (n = 144), corresponding values were 11.1% and 9.0%, respectively. In the dupilumab group, 23.5% achieved only WI-NRS ≥4-point reduction from baseline at week 24, and 11.1% achieved only IGA PN-S score 0 or 1 at week 24. In the placebo group, corresponding data were 10.1%, and 8.2%, respectively. Safety findings were consistent with the known dupilumab safety profile. More than one-third of dupilumab-treated patients achieved the multicomponent endpoint at week 24, constituting concurrent responses on both itch and skin lesions. However, more than two-thirds had clinically meaningful improvement by week 24, defined as either ≥4-point reduction in WI-NRS from baseline, IGA PN-S score 0/1, or both. Almost one-quarter of dupilumab-treated patients met only WI-NRS ≥4-point improvement at week 24, suggesting that skin lesion improvement may lag behind the improvement of itch. Conversely, one-ninth met only IGA PN-S score of 0 or 1 at week 24 suggesting that, in addition to the overlapping mechanisms by which dupilumab ameliorates pruritus and skin lesions, there are independent treatment effects on itch and skin remodelling. Safety was consistent with the known safety profile of dupilumab across approved indications.

338 Laboratory safety from a 16-week phase 3 study of dupilumab in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis

Abstract Many systemic therapies used for moderate-to-severe atopic dermatitis (AD) have immunosuppressive properties and necessitate laboratory screening and monitoring, adding to the treatment burden. Previous dupilumab studies in adults, adolescents and children aged 6–11 years with moderate-to-severe AD showed no clinically meaningful adverse changes in laboratory parameters. Here we evaluate hematology and chemistry laboratory safety data for dupilumab-treated children aged 6 months to 5 years with moderate-to-severe atopic dermatitis. Patients aged 6 months to 5 years with inadequately controlled moderate-to-severe AD were enrolled in LIBERTY AD PRESCHOOL (NCT03346434 part B), a randomized, double-blind placebo-controlled phase 3 study. 162 patients were randomized to either dupilumab 200/300 mg every 4 weeks (q4w; N = 83; baseline weight ≥5 &amp;lt;15 kg: 200 mg; ≥15 to &amp;lt;30 kg: 300 mg) or placebo (N = 79) for 16 weeks. From Day –14, all patients initiated standardized treatment with low-potency topical corticosteroids. Laboratory data was collected at baseline, weeks 4 and 16. At baseline, mean (SD) counts of hematology parameters were similar in both treatment groups: haemoglobin (dupilumab: 129.4 gL−1 [12]; placebo: 127.2 gL−1 [11.4]), lymphocyte (dupilumab: 4.6 × 109 L−1 [1.8]; placebo: 4.5 × 109 L−1 [1.7]), basophil (dupilumab: 0.07 × 109 L−1 [0.03]; placebo: 0.07 × 109 L−1 [0.04]), platelet (dupilumab: 397.7 × 109 L−1 [103.2]; placebo: 385.6 × 109 L−1 [112.9]) and eosinophils (dupilumab: 1.1 × 109 L−1 [0.7]; placebo: 1.1 × 109 L−1 [0.7]). Mean (SD) haemoglobin count in the dupilumab (128.4 × gL−1 [11]) and placebo groups (128.2 × gL−1 [11.2]), lymphocyte count in the dupilumab (4.20 × 109 L−1 [2.06]) and placebo groups (4.29 × 109 L−1 [1.52]) and basophil count in the dupilumab (0.07 × 109 L−1 [0.04]) and placebo groups (0.06 × 109 L−1 [0.03]) remained with the normal reference range for this population at week 16. The mean change (SD) in platelet count at week 16 was −16.3 × 109 L−1 (78.5) in the dupilumab group and +17.4 × 109 L−1 (106.6) in the placebo group. In the dupilumab treatment group, the mean eosinophil count increased at week 4 (mean change from baseline [SD]; + 0.48 × 109 L−1 [1.8]) and trended downward by week 16 (+0.31 × 109 L−1 [1.4]) while minimal changes were noted in the placebo group at week 4 (0.1 × 109 L−1 [0.7]) and week 16 (−0.2 × 109 L−1 [0.7]). The values for creatine kinase, alkaline phosphatase, lactate dehydrogenase, blood urea nitrogen, albumin and protein at week 16 remained within the normal reference range in all treatment groups. Two patients in the dupilumab 200/300 mg q4w arm of this study reported treatment-emergent adverse events of severe and moderate eosinophilia. Neither event was associated with clinical symptoms nor led to the discontinuation of the study treatment. No clinically meaningful changes in hematology and chemistry parameters in children aged 6 months to 5 years with moderate-to-severe AD were seen with 16 weeks of dupilumab treatment. These data demonstrate that, as with adults, adolescents and older children, routine laboratory monitoring is unnecessary in this younger population. Dupilumab was generally well tolerated with an acceptable safety profile.

341 Dupilumab improves itch and skin lesions in adults with prurigo nodularis regardless of prior use of immunosuppressants or phototherapy: post-hoc results from PRIME and PRIME2 clinical trials

Abstract Dupilumab is the only FDA-approved systemic therapy for prurigo nodularis (PN), however, immunosuppressants (IS) and phototherapy have been used off-label for the treatment of this condition. Patients with prior IS/phototherapy treatment may represent a more severe and/or treatment-refractory population of patients with PN. Report post-hoc efficacy of dupilumab in patients with PN, with or without prior use of IS or phototherapy for PN. LIBERTY-PN PRIME and PRIME2 (NCT04183335 and NCT04202679) are randomized, 24-week, phase 3 studies in adults with PN that is inadequately controlled by topical prescription therapies or for whom those therapies are not advisable. Primary outcomes included a ≥4-point improvement in the weekly average of Worst Itch Numerical Rating Scale (WI-NRS) from baseline to week 24, and an Investigator’s Global Assessment for PN stage (IGA PN-S) score of 0/1 (clear/almost clear) at week 24. Safety outcomes included the incidence of treatment-emergent adverse events (TEAEs). Among patients with PN, 8.0% reported prior use of phototherapy, and 36.7% reported prior use of IS; overall, 126 (dupilumab group, n = 62; placebo group, n = 64) patients with and 185 (dupilumab, n = 91; placebo, n = 94) patients without prior IS/phototherapy use were included. A larger proportion of patients with prior treatment vs. patients without prior treatment had severe disease, as measured by IGA PN-S (40.5% vs. 29.0%). The baseline WI-NRS score (SD) for overall patients with prior treatment was 8.6 (1.0) and for patients without prior treatment was 8.4 (1.0). At week 24, 67.7% vs. 15.6% of patients in the dupilumab vs. placebo groups with prior treatment (odds ratio [95% confidence interval]: 13.6 [3.7–49.7]; P &amp;lt; 0.0001), and 52.7% vs. 21.3% of patients without prior treatment (5.8 [2.4–14.0]; P &amp;lt; 0.0001) achieved improvement in WI-NRS. Similarly, 35.5% vs. 10.9% (3.1 [1.2–8.4]; P = 0.0162) of patients with and 53.8% vs. 21.3% (5.0 [2.3–10.8]; P &amp;lt; 0.0001) of those without prior treatment achieved IGA PN-S score of 0/1, respectively. TEAEs were reported by 43 (69.4%) vs. 34 (53.1%) patients (dupilumab vs. placebo groups) with and 54 (60.0%) vs. 55 (59.1%) without prior treatment, respectively. Patients treated with dupilumab experienced a greater and clinically meaningful improvement in itch and achieved skin that was clear/almost clear of nodules at week 24, regardless of prior use of IS/phototherapy for the treatment of PN. The incidence of TEAEs was generally consistent among patients with and without prior IS/phototherapy.