Safety Of Dupilumab Research Articles

Efficacy and safety of dupilumab in the treatment of Kimura's disease.

Kimura's disease (KD) is a rare chronic inflammatory condition characterized by nodules and lymphadenopathy in the head and neck region, exhibiting type II inflammation. Dupilumab is commonly used against type II inflammation. To evaluate the efficacy and safety of dupilumab in KD patients. The real-world study was conducted in a hospital in China. Six male patients with a mean age of 24.50 ± 15.47 years were treated with dupilumab following the same protocol as that for atopic dermatitis (AD). Clinical and laboratory indicators, such as maximum nodule diameter, blood eosinophil count, eosinophil percentage, and total serum IgE levels were assessed at baseline, Week 12 and Week 24. Adverse events were documented. Paired t-tests and one-way ANOVA were used for statistical analysis. The results showed significant reductions in the longest nodule diameter at Week 12 (P = 0.006) and Week 24 (P = 0.017) compared to baseline. Blood eosinophil count decreased by 57.95% (P = 0.024) at Week 12 and 90.59% (P = 0.030) at Week 24. Eosinophil percentage decreased by 58.44% (P = 0.026) at Week 12 and 89.37% (P = 0.013) at Week 24. Total serum IgE levels decreased by 78.02% (P = 0.040) at Week 12 and 89.55% (P = 0.031) at Week 24. The presence of AD did not affect the results. One patient experienced temporary facial erythema after 32 weeks of treatment, which resolved with topical treatment. No other adverse events were reported. Dupilumab demonstrated effectiveness in treating KD without severe adverse events.

Dupilumab in the treatment of severe adopic dermatitis and respiratory allergy: a case report

The use of biological targeted therapy for allergic diseases has significantly increased the effectiveness of the treatment of patients with atopic dermatitis, bronchial asthma, and combined allergopathology. Dupilumab, a monoclonal antibody drug that blocks signaling from IL-4 and IL-13, is one of the options for biological therapy aimed at modifying the Th2 immune response. The article discusses current ideas about the pathogenesis of allergic Th2-dependent inflammation, about the key mechanisms of the formation of atopic dermatosis and its role in inducing the progressive course of atopy. A clinical example of successful treatment of an 8-year-old child with severe atopic dermatitis, moderate partially controlled bronchial asthma, allergic rhinitis, and multisensitization to food and pollen allergens is given. The use of biological targeted therapy with dupilumab made it possible to achieve sustainable remission in the course of atopic dermatitis and bronchial asthma. The SCORAD index, which was 66.8 points before dupilumab treatment, decreased to 8.9 points. Immunobiological therapy with an IL-4Rα inhibitor, dupilumab, is indicated for patients with moderate to severe allergic diseases when it is not possible to achieve adequate control with standard treatment methods. The presented clinical case of the use of the drug contributes to the study of the clinical efficacy and safety of dupilumab during its long-term use.

509 - Dupilumab improves disease severity in children less than 12 years of age with moderate-severe AD: interim results from PEDISTAD real-world registry

Abstract Introduction In phase 3 studies, dupilumab significantly improved disease severity in children with moderate-to-severe atopic dermatitis (AD). However, the impact of this systemic treatment on children in real-world treatment settings is yet to be investigated. Objectives To report the real-world effectiveness and safety of dupilumab in children the PEDISTAD registry. Methods PEDISTAD (NCT03687359) is an ongoing, international, longitudinal, observational 10-year registry study in patients aged from 6 months to 11 years at enrollment with moderate-to-severe AD, whose disease is not adequately controlled by topical prescription therapies or for whom those therapies are medically inadvisable. This interim analysis measures the effect of dupilumab on Eczema Area and Severity Index (EASI) total score and %-affected body surface area (BSA) from therapy start to up to 3 years’ follow up. Safety was also evaluated. Results A total of 214 patients received dupilumab (median treatment observation period: 16.1 months; accumulated 3-year discontinuation rate: 13.3%). The proportion of patients with clear/mild AD (EASI score <7 [range 0–28]) increased from 20.8% at therapy start to 76.7% at last observation. The mean (±SE) EASI score decreased with dupilumab use, from 19.7±1.0 at therapy start to 6.1±0.8 at last observation. The proportion of patients with <10% BSA affected by AD increased from 12.6% at therapy start to 46.5% at last observation. The mean (± SE) BSA affected decreased from 38.3%±1.7 at therapy start to 17.1%±2.0 at last observation. 24.2% of patients had adverse events, including 2.4% serious adverse events. Conclusions Dupilumab treatment significantly improved disease severity in patients aged from 6 months to 11 years in real-world practice.

506 - Dupilumab is efficacious in patients with prurigo nodularis regardless of history of atopic comorbidities: pooled results from two phase 3 trials (LIBERTY-PN PRIME and PRIME2)

Abstract Introduction Prurigo nodularis (PN) is a chronic inflammatory skin condition characterized by severely itchy skin nodules. Nearly half of affected adult patients have a history of (or current) atopic comorbidity, such as atopic dermatitis (AD). Objective To report the efficacy and safety of dupilumab in patients with PN with or without history of atopic comorbidities, in a pre-specified analysis of pooled data from two phase 3 trials. Method In the randomized, double-blind, placebo-controlled, 24-week studies, LIBERTY-PN PRIME (NCT04183335) and PRIME2 (NCT04202679), adults with PN inadequately controlled by topical prescription therapies, were randomized 1:1 to dupilumab 300 mg every 2 weeks or matched placebo. Atopic patients were defined as patients with a physician-documented history, or current diagnosis, of at least one of the following atopic comorbidities: AD, allergic rhinitis/rhinoconjunctivitis, asthma, or food allergy. Efficacy was assessed from baseline to Week 24 through the Worst Itch Numerical Rating Scale (WI-NRS; 0–10), and the Investigator’s Global Assessment for PN-Stage score (IGA PN-S; 0–4). Results 311 patients were randomized (dupilumab n=153, atopic/non-atopic N=67/86; placebo n=158, atopic/non-atopic N=68/90). At Week 24, significantly more atopic and non-atopic dupilumab-treated patients achieved a ≥4-point improvement in WI-NRS (58.2%/59.3%), and an IGA PN-S score of 0 or 1 (52.2%/41.9%) vs placebo (20.6%/17.8% [nominal P<0.0001/P<0.0001] and 16.2%/17.8% [nominal P<0.0001/P=0.0005], respectively). The proportion of patients achieving concomitant ≥4-point improvement in WI-NRS and IGA PN-S score of 0 or 1 was higher for both dupilumab-treated atopic and non-atopic patients (37.3%/33.7%) vs placebo (7.4%/10.0% [nominal P=0.0057/P<0.007]). Overall safety was consistent with the known dupilumab safety profile, with no remarkable differences between atopic and non-atopic patients. Conclusion Dupilumab treatment improves itch and skin lesions in PN patients with and without a history of atopic comorbidities, indicating that underlying type 2 inflammation is present in patients with PN regardless of their history of atopic comorbidities.

539 - Baseline patient characteristics, physician-assessed effectiveness, patient-reported outcomes, and safety in adult atopic dermatitis patients in Japan treated with dupilumab: Real-world insights one year into the GLOBOSTAD multinational prospective observational study

Abstract Introduction Real-world studies complement randomized controlled trials (RCT), providing treatment-pattern and effectiveness data within a heterogenous population. In several RCTs, dupilumab has demonstrated a robust efficacy profile in patients with moderate-to-severe atopic dermatitis (AD). The main objectives of the ongoing GLOBOSTAD (NCT03992417) study are characterizing the patient population treated with dupilumab, their usage patterns, long-term effectiveness, and safety of dupilumab in real-world AD treatment. However, clinical practice details can differ among countries and/or regions. Objectives To give a comprehensive overview of patients in Japan enrolled in the GLOBOSTAD study –demographics, history of comorbidities, prior AD treatments, and reasons for initiating dupilumab treatment at baseline; to report on dupilumab effectiveness through physician-assessed AD clinical tools and patient-reported outcomes; and to provide a summary of adverse events one year after initiating dupilumab treatment. Methods The GLOBOSTAD five-year, multinational, prospective, observational study enrolled patients aged ≥12 years with moderate-to-severe AD. Patients received dupilumab based on country-specific prescribing information. In Japan, dupilumab is indicated for patients with moderate-to-severe AD who have not responded adequately to topical anti-­inflammatory treatments.1 Assessments were performed at baseline, 3 months (M; ±1M), 6M (±2M), and 12M (±2M). Data are reported as observed for enrollment/safety (N=118; data cutoff: March 2023) and follow-up (N=114) populations. Results Of the 118 patients enrolled in Japan in the GLOBOSTAD study, 69 (58.5%) were aged 18 to 39 years and 43 (36.4%) aged 40 to 64, with mean (standard deviation, SD) age of 37.2 (14.2) years. The population comprised 84 (71.2%) male and 34 (28.8%) female patients. Prior to enrollment, one or more comorbidities were reported in 66 (55.9%) patients, of which type 2 inflammatory comorbidities, such as allergic rhinitis (45; 38.1%), asthma (27; 22.9%), and food allergies (20; 16.9%), were the most frequently reported. Thirty-three (28.0%) patients reported using systemic AD treatments prior to enrollment, primarily systemic immunosuppressants (17; 14.4%) and systemic corticosteroids (13; 11.0%). Eighty (67.8%) patients reported using non-systemic treatments for AD, including topical corticosteroids (70; 59.3%) and topical calcineurin inhibitors (25; 21.2%). The predominant reason for initiating dupilumab treatment was previous treatment failure (95; 80.5%). Dupilumab treatment was initiated in 117 patients with a loading dose of 600 mg dupilumab, and in 1 patient with 300 mg dupilumab. During the study, mean (SD) Eczema Area and Severity Index (EASI; >21=severe; ≤7=mild/no disease) score rapidly improved from 30.2 (12.3) at baseline to 9.3 (10.3) at 3M, and further to 6.5 (8.2) at 6M and 4.6 (7.5) at the end of observation period (12M). Similarly, mean (SD) patient-reported pruritus Numerical Rating Scale (NRS) score improved from 5.6 (2.4) at baseline to 1.9 (2.1) at 3M, and further to 1.5 (1.9) at 6M and 1.2 (1.6) at 12M. Dupilumab-related adverse events were reported in 30 (25.4%) patients; no events led to dupilumab discontinuation. Conclusion Most adults with moderate-to-severe AD enrolled in the GLOBOSTAD study in Japan reported previously using systemic and/or non-systemic AD treatments; previous treatment failure was cited as the main reason for dupilumab initiation. In line with the local indication, in the 12 months prior to dupilumab initiation, reported systemic immunosuppressant use was less, whereas reported TCS/TCI use was greater, compared to the total GLOBOSTAD population.2 Real-world effectiveness of dupilumab was evaluated using clinical AD tools and patient-reported outcomes; EASI and pruritus NRS scores rapidly improved when patients initiated dupilumab treatment. Improved scores were sustained through the end of the one-year observation period, and safety data were consistent with previous studies. Similar to the overall population enrolled in the GLOBOSTAD study, patients in Japan achieved clinically meaningful improvements in AD signs/symptoms on initiating dupilumab ­treatment.

Dupilumab treatment improves signs, symptoms, quality of life, and work productivity in patients with atopic hand and foot dermatitis: Results from a phase 3, randomized, double-blind, placebo-controlled trial

Despite high disease burden, systemic treatment options for patients with atopic hand and/or foot dermatitis (H/F AD) are limited. To evaluate efficacy and safety of dupilumab in H/F AD using specific instruments for assessing disease severity on hands and feet. In this multicenter phase 3 trial, adults and adolescents with moderate-to-severe H/F AD were randomized to dupilumab monotherapy (regimen approved for generalized AD), or matched placebo. The primary endpoint was proportion of patients achieving Hand and Foot Investigator's Global Assessment score 0 or 1 at week 16. Secondary prespecified endpoints assessed the severity and extent of signs, symptom intensity (itch, pain), quality of life, and sleep. A total of 133 patients (adults=106, adolescents=27) were randomized to dupilumab (n=67) or placebo (n=66). At week 16, significantly more patients receiving dupilumab (n=27) than placebo (n=11) achieved Hand and Foot Investigator's Global Assessment score 0 or 1 (40.3% vs 16.7%; P=.003). All other prespecified endpoints were met. Safety was consistent with the known AD dupilumab profile. Short-term, 16-week treatment period. Dupilumab monotherapy resulted in significant improvements across different domains of H/F AD with acceptable safety, supporting dupilumab as a systemic treatment approach for this often difficult to treat condition.

Effectiveness of dupilumab in pediatric patients with a nummular phenotype of atopic dermatitis.

The nummular phenotype of atopic dermatitis is clinically characterized by pruritic, coin-shaped plaques that are frequently recalcitrant to treatment. In this study, a retrospective chart review was conducted to evaluate the effectiveness and safety of dupilumab in children with nummular lesions of dermatitis. Twelve out of 14 patients demonstrated significant clinical improvement at a median time of 2.5 months (interquartile range, 1-4) after dupilumab initiation. A single case of paradoxical psoriasiform eruption was the only side effect reported in our cohort.

Real-world outcomes of children treated with dupilumab for moderate-to-severe atopic dermatitis: a single-centre retrospective observational UK study.

Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis (AD) in patients aged ≥ 6 months. The aim of this study was to examine real-world outcomes and safety of dupilumab in British children with moderate-to-severe AD attending a tertiary referral paediatric centre. Skin and quality of life scores, adverse events and discontinuation rates were assessed. Patients aged ≤ 18 years with moderate-to-severe AD were included if they had skin scores recorded at baseline and at least one follow-up visit. Efficacy and safety were assessed using descriptive statistics. In this retrospective observational survey, 72 children/teenagers, with a median age of 14 years (range 7-18) were included. Oral systemic immunosuppressants had failed to control AD in 88% of children recruited. All patients commenced on dupilumab had pretreatment eczema skin scores consistent with moderate-to-severe disease, with a median Eczema Area and Severity Index (EASI) score of 25 [interquartile range (IQR) 20-31]. EASI scores decreased by a median of 94% (IQR 82-100) and remained consistently low over 10-52 months of the study, with a median EASI score at final follow-up of 2 (IQR 0-6). Of the 72 children, 8 (11%) were able to discontinue dupilumab as they were in remission. Nineteen (26%) experienced adverse events, most commonly conjunctivitis (12 patients; 17%). Eight (11%) discontinued dupilumab (six with ongoing inflammatory skin flares, one with severe allergic conjunctivitis, one with intercurrent Wilson disease). Dupilumab was highly effective in treating most children with moderate-to-severe AD with good safety outcomes in the real world. However, 10% of children may need alternative therapy because of drug ineffectiveness or side-effects.

An Observational Study of Early Treatment Response and Predictors of Dupilumab in the Treatment of Moderate‐to‐Severe Atopic Dermatitis

Background. Dupilumab has shown good effectiveness and safety in patients with moderate‐to‐severe atopic dermatitis. However, there is a lack of clinical data that focuses solely on the treatment response for the endpoint to observe the short‐term goal (12 weeks) in the treatment‐to‐target (T2T) concept. Study on predictors of early treatment response is also limited. Objective. To evaluate the early effectiveness and safety of dupilumab in the treatment of moderate‐to‐severe atopic dermatitis and to identify possible predictors of response. Methods. Using a retrospective study method, patients with moderate‐to‐severe atopic dermatitis who received dupilumab for ≥12 weeks at the Southwest Hospital between September 2019 and April 2022 were included. Results. Totally 16.25% of patients achieved EASI75 after 4 weeks and 53.75% achieved EASI75 after 12 weeks. SCORAD, EASI, and NRS were 50.17 ± 17.35, 13.51 ± 12.33 and 7.10 ± 1.82 in turn at baseline, and decreased to 29.94 ± 15.01, 6.97 ± 7.92, 3.64 ± 1.39 and 14.96 ± 10.31, 3.05 ± 4.16, 2.19 ± 1.09 after 4 and 12 weeks, respectively, with statistically significant differences (p < 0.01). After 12 weeks, the changes in peripheral blood eosinophil count (decreased from (0.60 ± 0.43) ∗ 10^9/L to (0.30 ± 0.21) ∗ 10^9/L), total IgE level (decreased from 547.00 (179.00, 2167.50) IU/ml to 216.50 (106.00, 825.00) IU/ml), and LDH (decreased from (166.11 ± 171.59) IU/L to (67.54 ± 70.68) IU/L) from baseline were significant (p < 0.01). Elevated peripheral blood eosinophil counts might be associated with an inadequate response to dupilumab (SCORAD12w: p = 0.007; EASI12w: p = 0.003; NRS12w: p = 0.030). The most common adverse events were reactions at the injection site (6/80) and conjunctivitis (4/80). Conclusion. Dupilumab showed good early effectiveness and safety in real‐world practice in Chinese patients with moderate‐to‐severe atopic dermatitis.

Two cases of dupilumab-responsive Kimura disease.

Kimura disease (KD) is a rare, chronic angiolymphoproliferative inflammatory disease appearing to be mostly restricted to the skin and soft tissue. Cutaneous involvement of KD includes head and/or neck nodules showing suggestive histological features, frequently associated with an atopic dermatitis-like or prurigo-like presentation. KD is challenging to treat, with high rate of recurrence using current therapeutic strategies. Evidence for involvement of a T-helper type 2 (Th2) immune response in KD pathogenesis has been found in previous studies. Consequently, this study aimed to determine the efficacy and safety of dupilumab, a human monoclonal antibody that inhibits signalling of key Th2 cytokines, interleukin (IL)-4 and IL-13, within a single-centre cohort of patients with cutaneous KD. Two adults with a diagnosis of refractory (failure of at least one treatment line) cutaneous-restricted KD based on clinical, biological, histological, molecular and imaging findings received dupilumab for KD, and showed dramatic response with a good safety profile.

Dupilumab in chronic rhinosinusitis with nasal polyps: Real life data in a multicentric Sicilian experience

ObjectiveThis study aimed to evaluate the effectiveness and safety of dupilumab during the first year of treatment in a real-life setting, focusing on improvement in nasal polyp score (NPS) as well as specific symptoms, quality of life and olfactory function. Methodology/principalA multicentric observational cohort study was carried out. A total of 170 patients were enrolled in the Otorhinolaryngology Unit of the three University Hospitals and considered for dupilumab therapy. All recorder characteristics were age (at the first dupilumab application visit), sex, smoke habits, previous local and systemic corticosteroid therapy, history of endoscopic sinus surgery, number of previous endoscopic sinus surgery, concomitant asthma, history of an allergic condition, immunoglobulin E (IgE), allergy to nonsteroidal anti-inflammatory drugs (NSAIDs), Aspirin Exacerbated Respiratory Disease (AERD), other comorbidities associated, blood eosinophils, nasal polyp score, sinonasal outcome test 22 (SNOT 22), sniffin' stick test, the start date of dupilumab therapy and number of doses of dupilumab and eventually, Dupilumab's adverse events related to administration. The Wilcoxon test for dependent samples was performed to compare variables. Statistical significance was assumed for p values < 0.05. ResultsA statistically significant reduction in SNOT-22 and NPS was shown at the 6th and 12th month compared to baseline values (p < 0.001 for both comparisons). A statistically significant increase value at the Sniffin' sticks test was shown in the 6th and 12th month compared to baseline values (p < 0.001 for both comparisons).At the 12-month follow-up, according to EUFOREA indications, all patients were considered to remain in treatment with dupilumab and continued the treatment because of a reduced NPS, improved quality of life and a reduced need for system corticosteroids.Dupilumab seemed to be well tolerated by all patients. Any adverse effect of the drug led to the quit of biological treatment. ConclusionsThis multi-centric real-life study supported the effectiveness of dupilumab as an add-on therapy to intranasal corticosteroids in patients with severe uncontrolled CRSwNP in improvement of quality of life, severity of symptoms, polyp size reduction and smell function. Furthermore, our data support the safety profile of monoclonal therapy with dupilumab.

Dupilumab and subcutaneous immunotherapy for the treatment of refractory moderate to severe atopic dermatitis: A preliminary report

Subcutaneous immunotherapy (SCIT) and dupilumab are important treatments for patients with moderate to severe atopic dermatitis (AD). However, in clinical practice, poor response to allergen immunotherapy (AIT) or dupilumab has been observed in some patients. It is unknown whether combining dupilumab and SCIT can improve treatment responses in patients with moderate to severe AD that is resistant to dupilumab or SCIT monotherapy. This single-centre, retrospective, observational, real-world study evaluated the efficacy and safety of dupilumab and SCIT for refractory moderate to severe AD. The data of ten patients with moderate to severe atopic dermatitis who were treated with dupilumab and SCIT were retrospectively analysed. The scoring atopic dermatitis (SCORAD) score, numerical rating scale (NRS), and atopic dermatitis control test (ADCT) scores and eosinophil and total IgE levels before and after add-on therapy were compared and analysed. The SCORAD, NRS, and ADCT scores decreased significantly at four and 12 weeks after the initiation of add-on therapy and plateaued during maintenance treatment. The eosinophil and total IgE levels were not significantly different before and after add-on therapy. No serious adverse reactions were reported in any patient during add-on therapy. This study indicates that the combination of dupilumab and SCIT safely improves the treatment response of patients with moderate to severe AD who are resistant to dupilumab or SCIT monotherapy.

Real-World Clinical Experience of Dupilumab in the Treatment of Chronic Palmo-Plantar Eczema in Patients with Moderate-Severe Atopic Dermatitis: 52-Week Follow-Up.

Background: Hand-foot eczema (HFE) are special locations of dermatitis, which are often associated with atopic dermatitis (AD) and have a significant negative impact on the quality of life, demanding a clinically relevant improvement. Objectives: To evaluate the effectiveness and safety of dupilumab in the treatment of eczema localized in hands and/or feet in patients with moderate-to-severe AD. Methods: Retrospective multicenter study of adult patients with HFE treated with dupilumab for their AD. Patients with other concomitantly systemic immunosuppressive treatments did not undergo a washout period. The severity of palmar and/or plantar involvement was assessed using the Physician Global Assessment (PGA) scale on a scale of 0 ( = clear) to 5 ( = very severe). Eczema Area and Severity Index (EASI) and NRS-pruritus scales were also evaluated. One hundred percent of patients reached week 16, while 67/84 reached week 52 of follow-up. Results: A total of 84 patients were included 86.69% of patients showed a reduction in PGA-Hand, and 80.34% in PGA-Foot at week 52, EASI improvement was reached by 83.55% of patients at week 16 and 87.35% at week 52. Reduction of pruritus (≥4 points in NRS-pruritus scale) was 73.01% at week 16 and 80.67% at week 52. No differences in response to dupilumab were observed in the different subtypes of palmo-plantar dermatitis. Conclusions: The results obtained in our study suggest that dupilumab may be an effective and safe therapeutic option for the treatment of dermatitis localized in hands and/or feet.

Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis

To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.

Effectiveness and safety of dupilumab in patients with severe hand eczema.

Effectiveness and safety of dupilumab in patients with severe hand eczema.

A clinical observational study on the preliminary effect of dupilumab in the treatment of severe asthma

Objective: To investigate the effect and safety of dupilumab in the treatment of patients with severe asthma in a preliminary clinical observational study. Methods: This study retrospectively analyzed the clinical data of 20 patients with severe asthma who received dupilumab for 4-12 months between 2019 and 2022 at the First Hospital of Guangzhou Medical University, comparing pre-and post-treatment laboratory data, oral glucocorticoid dose (OCS), asthma control test (ACT) and adverse effects. The median age of the 20 patients was 48.5 (41.0-52.8) years, including 14 males and 6 females. The clinical data of 10 patients treated with other biologic agents were further analyzed to determine the reasons for switching to biologic drug treatment and the efficacy of dupilumab in these patients. Paired t-tests or Wilcoxon signed-rank tests were used for comparisons. Mann-Whitney analysis was used for inter-group comparison, and chi-square test or Fisher test was used for inter-group comparisons of count data. Results: A total of 20 patients were included in this study. All 20 severe asthma phenotypes were type 2 (T2)-high and completed at least the first 4 months of treatment, including 17 patients who completed 12 months of treatment. Among patients who completed 4 months of treatment, the asthma exacerbation score decreased from 1.0(0.3-1.0) episodes/4 months to 0.0(0.0-1.0) episodes/4 months, P<0.001, and FEV1/FVC increased from 58.4% (50.5%-69.0%) to 66.9% (59.6%-77.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 15 (75%) to 9 (45%), P<0.05. Among patients who completed 12 months of treatment, the asthma exacerbation score decreased from 1.0(0.5-1.0) episodes/4 months to 0.0 (0.0-0.0) episodes/4 months, P<0.01, and FEV1/FVC increased from 57.9% (49.6%-67.8%) to 72.7% (64.6%-78.7%), P<0.01. The number of patients requiring OCS maintenance therapy decreased from 13 (76%) to 6 (35%), P<0.01. In 10 patients with a history of previous biologic therapy, the most common reasons for switching to a biologic were a poor response to previous monoclonal antibodies (40%) and loss of control of asthma symptom control after discontinuation of monoclonal antibodies (30%). The remaining reasons were patients' uncontrolled symptoms of chronic rhinosinusitis (20%) and irregular or underdosed use of previous biologics (10%). After 4 months of switching to dupilumab, 10 patients experienced varying degrees of improvement in asthma control. Conclusions: The application of dupilumab for the treatment of T2-high severe asthma showed good efficacy and few adverse effects. Biologically targeted therapy is an important treatment approach to achieving better control of severe asthma.

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.

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.