Peak Pruritus Numerical Rating Scale Research Articles

The assessment of dupilumab in children with moderate-to-severe asthma and comorbid type 2 inflammatory diseases

BackgroundDupilumab inhibiting the signaling of interleukin(IL)-4 and IL-13 was recommended for the treatment of severe asthma in children ≥ 6 years old according to the Global Initiative for Asthma (GINA,2024).This study aimed to analyse the efficacy and safety of dupilumab in paediatric patients with moderate-to-severe asthma and comorbid type 2 inflammatory disease in a real-world population.MethodsWe evaluated the medical records of paediatric patients with moderate-to-severe asthma and comorbid type 2 inflammatory diseases, such as atopic dermatitis (AD) and allergic rhinitis (AR), receiving dupilumab treatment.ResultsTwenty-five children (16 boys; mean age, 9.32 ± 2.58 years) were included. All the patients were diagnosed with moderate-to-severe asthma, 92% (23/25) with AR, and 64.0% (16/25) with AD. Among the 25 patients, no severe adverse reactions occurred, the times of severe asthma exacerbation were significantly lower, and the Asthma Control Test (ACT) / Child-Asthma Control Test (C-ACT) scores were significantly higher than those before the 24-week dupilumab treatment (all P = 0.00). The Patient-Oriented Eczema Measure(POEM) and Peak Pruritus Numerical Rating Scale(NRS), Rhinitis Four-point, and Rhinitis Visual Analogue Scale(VAS) scores were significantly lower than those at baseline (all P < 0.05). After receiving 24-week dupilumab treatment, the serum total immunoglobulin E (tIgE) and fractional exhaled nitric oxide (FeNO) level were reduced by 56.54% and 70.47% respectively at the 24th week (P = 0.00); the lung function parameters including large airways such as percent predicted forced expiratory volume in one second (FEV1% pred) and small airways like percent predicted forced expiratory flow at 25–75%, were significantly higher than those before dupilumab (all P < 0.05).ConclusionsDupilumab reduced asthma exacerbations and improved symptom control without severe adverse reactions in paediatric patients with moderate-to-severe asthma and comorbid type 2 inflammatory diseases. It also decreased biomarkers of type 2 inflammation and improved lung function parameters, including both large and small airways. Considering the racial diversity, a large real-world study in China is required to confirm the role of dupilumab in paediatric patients with moderate-to-severe asthma and comorbid type 2 inflammatory diseases.

Efficacy and Safety of Nemolizumab in Patients With Moderate to Severe Prurigo Nodularis

Prurigo nodularis (PN) is a chronic and debilitating skin condition, characterized by intense itch with multiple nodular lesions. Nemolizumab demonstrated significant improvements in itch and skin nodules in adults with moderate to severe PN in a previous 16-week phase 3 study (OLYMPIA 2). To assess the efficacy and occurrence of adverse events in adults with moderate to severe PN treated with nemolizumab vs those receiving placebo. OLYMPIA 1 was a multicenter, placebo-controlled, phase 3 randomized clinical trial, conducted from August 2020 to March 2023 at 77 centers across 10 countries in adults with moderate to severe PN (at least 20 nodules and an Investigator's Global Assessment [IGA] score ≥3) and Peak Pruritus Numerical Rating Scale (PP-NRS) score of at least 7.0; consisted of screening (up to 4 weeks), 24-week treatment, and 8-week follow-up periods. Patients were randomized (2:1) to nemolizumab monotherapy, 30 mg or 60 mg (depending on baseline weight of less than 90 kg vs 90 kg or greater, respectively), or matching placebo administered every 4 weeks for 24 weeks. The primary end points were the proportion of patients with itch response (≥4-point improvement from baseline in weekly average PP-NRS) and IGA success (score of 0/1 [clear/almost clear] and 2-grade or more improvement from baseline) at week 16. Of 286 patients (mean [SD] age, 57.5 [13.0] years; mean [SD] body weight, 85.0 [20.7] kg; 166 [58.0%] female), 190 were randomized to receive nemolizumab, and 96 were randomized to placebo. A significantly greater proportion of patients assigned to nemolizumab vs placebo achieved itch response (111/190 [58.4%] vs 16/96 [16.7%]; Δ, 40.1% [95% CI, 29.4%-50.8%]; P < .001) and IGA success (50/190 [26.3%] vs 7/96 [7.3%]; Δ, 14.6% [95% CI, 6.7%-22.6%]; P = .003) at week 16. At week 24, the proportion of patients with itch response was 58.3% vs 20.4% (Δ, 38.7% [95% CI, 27.5%-49.9%]) in the ad hoc analysis, and IGA success was 58/190 (30.5%) vs 9/96 (9.4%) (Δ, 19.2% [95% CI, 10.3%-28.1%]) in the nemolizumab-treated vs placebo group. During the treatment period, 134 patients (71.7%) receiving nemolizumab vs 62 patients (65.3%) receiving placebo had at least 1 adverse event; most events were of mild to moderate severity. In this randomized clinical trial, nemolizumab monotherapy led to clinically meaningful and statistically significant improvements in core signs and symptoms of PN. ClinicalTrials.gov Identifier: NCT04501666.

Achievement of No-to-minimal Itch and Sleep Improvement with Tapinarof Cream 1% Once Daily in Two Pivotal Phase 3 Trials in Adults and Children Down to 2 Years of Age with Atopic Dermatitis

Introduction: Itch frequently causes sleep disturbance in patients with atopic dermatitis (AD). The gold-standard Peak Pruritus Numerical Rating Scale (PP-NRS) improvement from baseline is 4 points; however, more stringent outcomes include achieving no-to-minimal itch (PP-NRS ≤1). Tapinarof cream 1% once daily (QD) demonstrated superior efficacy, including itch reduction, versus vehicle and was well tolerated in adults and children down to 2 years of age with AD in the ADORING 1 and 2 pivotal phase 3 trials. Here we present highly stringent itch outcomes and sleep improvement with tapinarof from these trials. Methods: In ADORING 1 and 2, patients with a Validated Investigator Global Assessment for Atopic Dermatitis™ score ≥3 (moderate or severe), Eczema Area and Severity Index score ≥6, and body surface area involvement of 5–35% were randomized to tapinarof cream or vehicle QD for 8 weeks. Stringent PP-NRS assessments were analyzed post hoc and included achieving no‑to‑minimal itch (PP-NRS ≤1) or PP-NRS score &lt;2. Mean weekly PP-NRS scores were assessed on an 11-point scale (0 indicates “no itch” and 10 is “worst imaginable itch”). The Patient Oriented Eczema Measure (POEM) question 2 evaluated sleep disturbance on a 5-point scale (0 indicates “no days” and 4 is “every day”); outcomes were pooled and stratified by age. Results: 407 and 406 patients were randomized in ADORING 1 and 2. Mean baseline scores were similar across ADORING 1 and 2 treatment groups: PP-NRS, 6.7 and 6.8; pooled POEM sleep disturbance scores, 2.0 (aged ≥12 years) and 2.4 (&lt;12 years), respectively. Statistically significant achievement of no-to-minimal itch (PP-NRS ≤1), PP-NRS &lt;2, and improvement in sleep were achieved with tapinarof versus vehicle as early as Week 1, the first assessment, and continued through Week 8. Stringent itch outcomes were achieved with tapinarof versus vehicle at Week 8: no-to-minimal itch, 31.4% versus 17.4% (P=0.0072) and 33.0% versus 14.0% (P=0.0003); and PP-NRS &lt;2, 48.1% versus 28.4% (P=0.0006) and 46.8% versus 19.6% (P&lt;0.0001) in ADORING 1 and 2, respectively. Sleep scores improved with tapinarof versus vehicle at Week 8: –1.4 versus –0.8 (≥12 years); –1.7 versus –1.0 (&lt;12 years; both P&lt;0.0001). Conclusion: Tapinarof cream 1% QD demonstrated early, significant, and meaningful achievement of no-to-minimal itch and improvement of sleep in adults and children down to 2 years of age with AD.

Dupilumab Demonstrates a Higher Likelihood of Achieving Improvements in Signs, Symptoms, and Quality of Life vs. Tralokinumab at Week 16: Results from a Bucher Indirect Treatment Comparison

Background: Dupilumab and tralokinumab are biologics approved by the US Food and Drug Administration (FDA) for the treatment of patients with moderate-to-severe atopic dermatitis (AD), aged ≥6 months and ≥12 years, respectively. Dupilumab and tralokinumab have demonstrated efficacy and safety in clinical trials. However, no direct head-to-head trials have been performed to compare the efficacy of dupilumab vs tralokinumab. The Bucher indirect treatment comparison (ITC) is a robust, placebo-adjusted, and accepted method to evaluate the relative efficacy of drugs in the absence of direct comparisons. The objective of this analysis was to report results from a Bucher ITC comparing the efficacy of dupilumab+topical corticosteroid (TCS) vs tralokinumab+TCS at Week 16. Methods: The placebo-adjusted Bucher ITC included published data from the two similarly designed phase 3 trials, LIBERTY AD CHRONOS (NCT02260986) and ECZTRA 3 (NCT03363854). For both studies, data from the 16-week period were used, employing non-responder imputation, with the following doses: 300mg dupilumab every 2 weeks (q2w)+TCS or placebo+TCS, and 300mg tralokinumab q2w+TCS or placebo+TCS. The evaluated endpoints included the proportions of patients achieving an Investigator’s Global Assessment score 0/1 (IGA 0/1; clear/almost clear), 75% and 90% improvements from baseline in Eczema Area and Severity Index (EASI-75 and EASI-90), ≥4-point improvement from baseline in the Peak Pruritus Numerical Rating Scale score (PP-NRS &gt;4), and ≥4-point improvement from baseline in the Dermatology Life Quality Index (DLQI &gt;4). The Bucher ITC with the frequentist approach was performed using R software (v 4.20; netmeta package) with a fixed-effect model. Results were reported as odds ratio (OR) with 95% confidence interval (CI). Results: A total of 801 patients (LIBERTY AD CHRONOS: placebo+TCS: 315; dupilumab+TCS: 106; ECZTRA 3: placebo+TCS: 127; tralokinumab+TCS: 253) were included in the Bucher ITC. Baseline disease characteristics indicated comparable severity between the two trial populations based on IGA and PP-NRS. However, CHRONOS showed slightly higher baseline EASI scores (median [Q1, Q3] score 30.9 [22.3, 41.6] vs. ECZTRA 3: 24.7 [18.4, 35.9]), while ECZTRA 3 showed slightly higher DLQI scores (median [Q1, Q3] score 18.0 [12.0, 23.0] vs. CHRONOS: 13.5 [8.0, 20.0]). Patients treated with dupilumab+TCS had a significantly higher likelihood of achieving IGA 0/1 (OR=2.49, 95%CI 1.24–5.00), EASI-75 (OR=3.21, 95%CI 1.66–6.19), EASI-90 (OR=2.92, 95%CI 1.41–6.02), PP-NRS ≥4 (OR=3.62, 95%CI 1.87–7.00), and DLQI ≥4 (OR=2.16, 95%CI 1.03–4.54) at Week 16 vs those treated with tralokinumab+TCS. Conclusions: A placebo-adjusted Bucher ITC showed that the likelihood of achieving improvements in signs, symptom, and quality of life is significantly higher for patients treated with dupilumab+TCS vs tralokinumab+TCS at Week 16.

Long-term efficacy and safety of stapokibart for moderate-to-severe atopic dermatitis: 52-week results from a phase 3 trial.

Management of moderate-to-severe atopic dermatitis (AD) needs long-term therapy. Stapokibart is a humanized monoclonal antibody targeting interleukin-4 receptor α subunit (IL-4Rα), a shared receptor for IL-4 and IL-13 which are key pathogenic drivers of AD. In a pivotal phase 3 trial (NCT05265923), significant higher proportions of adult AD patients receiving stapokibart than placebo achieved ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75; 66.9% vs. 25.8%) and Investigator's Global Assessment (IGA) score of 0/1 with ≥2-point reduction (44.2% vs. 16.1%) at Week 16. Herein, we report long-term (52 weeks) efficacy and safety of stapokibart from this trial. After 16-week double-blind treatment completed, patients in both stapokibart and placebo groups entered a 36-week maintenance treatment period and received stapokibart 300 mg every 2 weeks. Concomitant use of topical medications for AD was permitted throughout the maintenance period. Of 476 patients entering maintenance period, 430 completed the treatment. At Week 52, EASI-75 was achieved in 92.5% of patients continuing stapokibart and 88.7% of those switching from placebo to stapokibart, respectively; an IGA score of 0 or 1 with a ≥2-point reduction was achieved in 67.3% and 64.2% of patients, respectively; a ≥4-point reduction in weekly average of daily Peak Pruritus Numerical Rating Scale (PP-NRS) was achieved in 67.3% and 60.5% of patients, respectively. Over the 52-week treatment period, 88.1% of patients reported treatment-emergent adverse events, most were mild or moderate. Long-term treatment with stapokibart demonstrated a sustained efficacy and favorable safety profile in adults with moderate-to-severe AD.

Unveiling the Impact of Moderate and Severe Atopic Dermatitis: Insights on Burden, Clinical Characteristics, and Healthcare Resource Utilization in Adult Greek Patients from the APOLO Cross-Sectional Study.

Background: Moderate to severe (M2S) atopic dermatitis (AD) is a chronic condition impacting individuals, society, and healthcare systems. Considering the changing M2S-AD treatment landscape, this study assesses the M2S-AD burden in patients reaching referral centers in Greece. Methods: This was a multicenter, cross-sectional study. Patients aged 12 years or older with clinically diagnosed M2S-AD were enrolled. Data collected included clinical practice assessments and the following validated patient-reported instruments: Dermatology Life Quality Index (DLQI); EuroQol-5 Dimensions-3 Level scale (EQ-5D-3L); Patient Oriented Eczema Measure (POEM); Peak Pruritus Numerical Rating Scale (PP-NRS); and Work Productivity and Activity Impairment: General Health (WPAI:GH). A pain frequency/intensity/cause questionnaire and a sleep disturbance scale were also used. Results: Outcomes of 184 adults (51.1% female) with M2S-AD based on the Eczema Area and Severity Index (EASI) are presented (n = 117 moderate; n = 67 severe). Among the patients, 14.8% were obese, 59.2% had allergic comorbidities, and 88.0% were receiving AD-specific therapy (systemic: 38.6%). The median age, disease duration, body surface area, and total EASI scores were 38.8 years, 11.8 years, 30.0%, and 16.9, respectively. The median DLQI score was 12.0, with 'symptoms/feelings' being the most affected domain. EQ-5D dimensions 'anxiety/depression' and 'pain/discomfort' were also affected (65.2% and 64.1% reporting problems, respectively). The median POEM score was 17.0. Pain, severe pruritus (PP-NRS ≥ 7), and sleep disturbance were reported by 80.4%, 62.0%, and 88.5%, respectively. The median WPAI:GH 'work productivity loss' and 'activity impairment' scores were 23.8% and 30.0%, respectively. Conclusions: Both moderate and severe AD patients reaching Greek specialized centers experience significant symptom burden and impairments in quality of life, sleep, work, and daily activities.

Real-World Evaluation of the Effectiveness and Safety of Dupilumab in Bullous Pemphigoid: An Ambispective Multicenter Case Series.

Bullous pemphigoid affects elderly individuals with multiple comorbidities, making conventional treatments unsuitable. Evaluate the effectiveness and safety of dupilumab in the treatment of bullous pemphigoid. A multicenter ambispective cohort study was conducted in 34 hospitals. Patients with bullous pemphigoid treated with Dupilumab were included. Most of patients (97.1%) received an initial 600 mg dose followed by 300 mg every two weeks. The primary outcome was the proportion of patients achieving complete remission within 4 weeks, defined as Investigator Global Assessment score of 0 or 1. Complete remission at weeks 16, 24, and 52, adverse events, reductions in peak pruritus numerical rating scale, and systemic glucocorticoid use were also assessed. The study included 103 patients with a median age of 77.3 years, 58.0% male. Complete remission was achieved by 53.4% within 4 weeks and 95.7% by week 52. Peak pruritus scale reduced by 70.0% by week 4 and was completely controlled by week 24. Thirteen patients presented adverse events, most of which were mild. Systemic glucocorticoid use reduced by 82.1% by week 52. Shorter disease duration and exclusive cutaneous involvement predicted better response at 16 weeks. No differences in response rates to dupilumab were observed between drug-associated bullous pemphigoid and idiopathic cases. No significant difference in response rates was observed between patients treated with dupilumab in monotherapy and those receiving dupilumab with concomitant treatments. Dupilumab is effective, rapid, and safe in managing bullous pemphigoid, reducing the need for corticosteroids and other treatments. Early initiation and exclusive skin involvement predict better outcomes.

Effectiveness and safety of upadacitinib retreatment after withdrawal in moderate-to-severe atopic dermatitis: a retrospective study.

Upadacitinib, a janus kinase 1 (JAK1) inhibitor, is effective for moderate-to-severe atopic dermatitis (AD). Upadacitinib treatment may be discontinued in some patients, however, the effectiveness and safety of retreatment after its withdrawal have not been precisely examined in real-world practice. To evaluate the effectiveness and safety of upadacitinib retreatment after withdrawal in real-world clinical practice for Japanese AD patients. This retrospective study included 62 Japanese patients with moderate-to-severe AD treated with upadacitinib 15 mg (n = 38) or 30 mg (n = 24). Effectiveness was assessed using eczema area severity index (EASI) and peak pruritus numerical rating scale (PP-NRS) before treatment (baseline), at time-periods of discontinuation, retreatment, and week 12 after retreatment of upadacitinib. Safety was evaluated through the incidence of treatment-emergent adverse events (TEAE). EASI and PP-NRS scores significantly decreased at week 12 after retreatment of upadacitinib compared to baseline in both 15 mg and 30 mg groups. Achievement rates of EASI 75, EASI 90, and EASI 100 at week 12 after retreatment were 83.8%, 56.8%, and 18.9% in 15 mg group, and 87.0%, 56.5%, and 17.4% in 30 mg group, respectively. TEAEs were mild or moderate, and no serious adverse events or deaths were reported. Retreatment of upadacitinib after withdrawal effectively improved clinical signs and pruritus in patients with AD, with a manageable safety profile, supporting its use for long-term management of AD.

Effects of Tralokinumab on Clinical and Laboratory Indexes in Atopic Dermatitis: A 24-Week Real-World Study.

Background: Tralokinumab, a monoclonal anti-IL-13 antibody, is approved for treating atopic dermatitis (AD). Real-world data on its effectiveness and safety are limited. Objective: To evaluate the real-world effectiveness and safety of tralokinumab and the transition of laboratory indexes during 24-week treatment for AD patients. Methods: This retrospective study included 104 patients with moderate-to-severe AD treated with tralokinumab 300 mg every 2 weeks after primary 600 mg. Clinical and laboratory indexes were assessed until week 24. Results: At week 24, achievement rates of Eczema Area and Severity Index 75 (EASI 75), EASI 90, and investigator's global assessment 0 out of 1 in systemic therapy-naïve patients, 83.3%, 72.2%, and 44.4%, respectively, were higher than those in systemic therapy-experienced patients, 46.7%, 20.0%, and 6.7%, respectively. Serum levels of immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and lactate dehydrogenase (LDH) significantly decreased at week 24, whereas neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation response index (SIRI) significantly decreased at week 12 from baseline. Twenty-nine patients (27.9%) experienced mild treatment-emergent adverse events. Conclusions: Tralokinumab treatment showed prosperous therapeutic effects and good tolerability in real-world practice for AD, with higher effectiveness in patients without prior systemic therapy compared with those with prior systemic therapy. Tralokinumab treatment significantly decreased clinical and laboratory indexes, EASI, Peak Pruritus-Numerical Rating Scale, IgE, TARC, LDH, NLR, and SIRI.

Cost per responder analysis of abrocitinib versus dupilumab in moderate to severe atopic dermatitis.

The JADE COMPARE was a multicenter, phase 3 randomized, double-blind, placebo-controlled trial with the objective of comparing the 16-week efficacy and safety of oral abrocitinib 100 or 200 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo in adults with moderate-to-severe atopic dermatitis (AD). Pharmacoeconomic evaluation of these new drugs for AD is lacking. The objective of our study was to compare the cost per responder of abrocitinib versus dupilumab in patients with AD using the data from the JADE COMPARE trial. The cost per responder was calculated by multiplying the cost of treatment by the number needed to treat for each therapy, as obtained from the JADE COMPARE trial. The 12-week primary endpoint was the Investigator global assessment (IGA) 0/1 and eczema area and severity index improvement of at least 75% (EASI75) response rate. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [PP-NRS; scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16. The cost per responder model was based on the perspective of the Italian National Health System. Regarding the costs of drugs, ex-factory wholesale purchase prices were used, including the mandatory discounts according to the national legislation (5% discount, plus a further 5% reduction on the discount result). Abrocitinib 100 mg and 200 mg have flat price in Italy. The 12-week IGA 0/1 cost per responder was € 3955.77 and € 2984.94 for abrocitinib 100 mg and 200 mg, respectively, versus € 7467.96 for dupilumab; as for 12-week EASI75 the cost were € 2463.30 and € 2057.58 vs. € 4705.09, respectively. As far as the secondary end points, the costs per responder were always lower for abrocitinib 100 and 200 mg compared to dupilumab, including the PP-NRS (€ 3791.55 and € 2451.22, vs. € 6462.65), the IGA 0/1 at week 16 (€ 6931.05 and € 4854.15 vs. € 8787.85) and the EASI75 at week 16 (€ 3984.75 and € 3381.00 vs. € 5197.45). According to JADE COMPARE trial data, the costs per responder of abrocitinib were considerably lower than dupilumab. The results of the study are limited to the short time frame of JADE COMPARE trial.

Validation of the Peak Pruritus-Numerical Rating Scale in patients with chronic plaque psoriasis: results from a phase 2 study.

Pruritus is a common, bothersome symptom for patients with mild-to-moderate plaque psoriasis (PsO), yet no validated scale assesses it in this patient population. We aimed to validate the Peak Pruritus-Numerical Rating Scale (PP-NRS) using data from a Phase 2b study investigating the efficacy of brepocitinib in patients with mild-to-moderate chronic PsO. Patients completed the PP-NRS daily from baseline for the first 2 weeks after the dose administration and subsequently only on visit days. Test-retest reliability (intraclass correlation coefficient [ICC]), construct validity (known group validity and convergent validity), ability to detect change, and meaningful within-patient change (MWPC) were evaluated using correlation and regression analyses. The PP-NRS demonstrated acceptable test-retest reliability (ICC: 0.86-0.89). Known-group evidence demonstrated that PP-NRS scores could discriminate between different degrees of disease severity. Convergent validity was supported by significant correlation coefficients between the PP-NRS and Patient Global Assessment (PtGA), Dermatology Life Quality Index, and Psoriasis Symptom Inventory, which generally exceeded 0.50. The ability to detect change was evidenced by an approximately linear relationship between changes in PP-NRS and Physician Global Assessment or PtGA of psoriasis scores. The value of 2.8 was determined as the MWPC for the PP-NRS. PP-NRS is a reliable, practical test for assessing pruritus in mild-to-moderate PsO clinical trials. NCT03850483.

Long-Term Efficacy and Safety of Stapokibart in Adults with Moderate-to-Severe Atopic Dermatitis: An Open-Label Extension, Nonrandomized Clinical Trial.

Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300mg every 2weeks up to 52weeks. Efficacy outcomes included the proportions of patients with ≥50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥2-point reduction was achieved in 39.3% of patients at week16, increasing to 58.9% at week52. The proportions of patients with ≥3-point and ≥4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. Long-term treatment with stapokibart for 52weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).

Attentiveness and mental health in adolescents with moderate-to-severe atopic dermatitis without ADHD

Patients with moderate-to-severe atopic dermatitis (AD) experience intense chronic itch and impaired sleep. Reports from parents and teachers suggest that AD patients may also have attention problems. However, attention has not yet been directly assessed in AD patients. We utilized an objective, computer-based continuous performance test (CPT) validated for use in attention-deficit/hyperactivity disorder (ADHD) diagnosis to formally evaluate attention in adolescent AD subjects. This was a single-visit, cross-sectional, non-interventional study of moderate-to-severe (Investigator’s Global Assessment [IGA] ≥ 3) AD subjects aged 12–17 years without clinician-diagnosed ADHD. Attention was evaluated using two performance-based measures: Conners, CPT-3 and the Stroop Color and Word Test. The primary parameter was CPT-3 detectability (d’) measure. Lesional severity measures included Eczema Area and Severity Index (EASI) and body surface area (BSA) involvement. Subjects completed self-report rating scales assessing sensory responsiveness patterns (Adult/Adolescent Sensory Profile [AASP]), itch (Peak Pruritus Numerical Rating Scale [PP-NRS]), skin pain, quality of life, sleep, anxiety, and depressive symptoms. A total of 44 subjects were included in the study (61.4% female; mean age 15.0 [SD 1.78] years; mean EASI 20.4 [SD 7.8]; mean PP-NRS 7.0 [SD 1.8]). Results indicated substantial disease impact on sleep, quality of life, and comorbid anxiety and depressive symptoms. The mean (SD) Conners, CPT-3 dʹ T-score was 48.7 (SD 10.7), similar to the expected mean from a randomly selected age/gender-matched sample of the general population (50 [SD 10], by definition). Overall, 13.6% of subjects exhibited a dʹ T-score ≥ 60 (clinically significant poor performance), which was not greater than the expected general population value (15.9%). Subject-level data review by two psychologists determined that only 2 subjects demonstrated an overall response pattern that clearly indicated attention deficit. Many subjects had atypical sensory responsiveness profiles: sensory hypersensitivity (38.6%), sensory avoidance (50%), and low registration (hypo-sensitivity, 36.4%). Adolescents with moderate-to-severe AD without existing ADHD diagnosis did not demonstrate greater attention problems on performance-based measures than would be expected in age/gender-matched peers.Trial registration NCT05203380.

A prospective observational cohort study comparing the treatment effectiveness and safety of ciclosporin, dupilumab and methotrexate in adult and paediatric patients with atopic dermatitis: results from the UK-Irish A-STAR register.

The main conventional systemic atopic dermatitis (AD) treatments are methotrexate (MTX) and ciclosporin (CyA). Dupilumab was the first novel systemic agent to enter routine clinical practice. There are no head-to-head randomised controlled trials or real-world studies comparing these agents directly. Network meta-analyses provide indirect comparative efficacy and safety data and have shown strong evidence for dupilumab and CyA. The aim of this study was to compare the real-world clinical effectiveness and safety of CyA, dupilumab and MTX in AD. We compared the effectiveness and safety of these systemic agents in a prospective observational cohort study of adult and paediatric patients recruited into the UK-Irish Atopic eczema Systemic TherApy Register (A-STAR). Treatment effectiveness measures included Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), Peak Pruritus Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI) and children's DLQI (cDLQI). Minimum duration of treatment was 28 days and follow-up was 12 months. Adjusted Cox-regression was used to compare the hazards of achieving EASI-50, EASI-75 and EASI-90 over time, and linear mixed-effects models were used to estimate changes in efficacy scores. Treatment safety was assessed by examining adverse events (AEs) at follow-up visits. 488 patients (n=311 adults and n=177 children/adolescents) on dupilumab (n=282), methotrexate (n=149), or CyA (n=57) were included. CyA and MTX were primarily used first line, while dupilumab was mainly a second line systemic as per UK National Institute of Clinical and Care Excellence (NICE) recommendations. EASI-50, EASI-75 and EASI-90 were achieved more rapidly in the dupilumab and CyA groups compared to MTX. After adjustment for previous severity, the reduction in EASI, POEM, PP-NRS and DLQI was greater for patients treated with dupilumab compared to MTX. In severe patients the reduction in EASI, POEM, and PP-NRS was even greater with CyA. The incidence of AEs was similar across groups (734, 654 and 594 per 10,000 person-month on CyA, dupilumab and MTX respectively). This real-world comparison of CyA, dupilumab and MTX in AD suggests that dupilumab is consistently more effective than MTX and that CyA is most effective in very severe disease within one follow-up year.

Nemolizumab with concomitant topical therapy in adolescents and adults with moderate-to-severe atopic dermatitis (ARCADIA 1 and ARCADIA 2): results from two replicate, double-blind, randomised controlled phase 3 trials

Nemolizumab, an interleukin (IL)-31 receptor subunit α antagonist, inhibits the IL-31 pathway of itch and skin inflammation in atopic dermatitis. Two international phase 3 studies were done to assess the efficacy and safety of nemolizumab in atopic dermatitis. In this Article we report results for the 16-week initial treatment period of both trials. ARCADIA 1 and ARCADIA 2 were identical 48-week randomised, double-blind, placebo-controlled phase 3 trials in adult and adolescent participants (aged ≥12 years) with moderate-to-severe atopic dermatitis, associated pruritus, and inadequate response to topical steroids. Participants were enrolled from 281 clinics, hospitals, and academic centres in 22 countries across both trials, and were randomly assigned (2:1) to receive nemolizumab 30 mg subcutaneously (baseline loading dose 60 mg) or matching placebo once every 4 weeks with background topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI; ie, TCS-TCI background treatment). Randomisation was done via interactive response technology and stratified by baseline disease and pruritus severity. Study staff and participants were masked throughout the study, with outcome assessors masked until database lock. Coprimary endpoints at week 16 post-baseline were Investigator's Global Assessment (IGA) success (score of 0 [clear skin] or 1 [almost clear skin] with a ≥2-point improvement from baseline) and at least 75% improvement in Eczema Area and Severity Index score from baseline (EASI-75 response). Outcome rates were compared between groups with the Cochran-Mantel-Haenszel test adjusting for randomisation strata. The key secondary endpoints were the proportion of participants with Peak Pruritus Numerical Rating Scale (PP-NRS) score improvement of at least 4 points at weeks 1, 2, 4, and 16; PP-NRS score below 2 at weeks 4 and 16; Sleep Disturbance Numerical Rating Scale score improvement of at least 4 points at week 16; EASI-75 response plus PP-NRS score improvement of at least 4 points at week 16; and IGA success plus PP-NRS score improvement of at least 4 points at week 16. Efficacy analyses were done on an intention-to-treat basis; safety analyses included all participants who received one dose of nemolizumab or placebo. Both studies are completed (ClinicalTrials.gov: ARCADIA 1, NCT03985943 and ARCADIA 2, NCT03989349). Between Aug 9, 2019, and Nov 2, 2022, 1728 participants were enrolled across both trials: 1142 were allocated to nemolizumab plus TCS-TCI (620 in ARCADIA 1 and 522 in ARCADIA 2) and 586 to placebo plus TCS-TCI (321 in ARCADIA 1 and 265 in ARCADIA 2). ARCADIA 1 included 500 (53%) male participants and 441 (47%) female participants, and ARCADIA 2 included 381 (48%) male participants and 406 (52%) female participants. Mean age ranged from 33·3 (SD 15·6) years to 35·2 (17·0) years across the treatment groups. Both trials met the coprimary endpoints; at week 16, a greater proportion of participants receiving nemolizumab plus TCS-TCI versus placebo plus TCS-TCI had IGA success (ARCADIA 1: 221 [36%] of 620 vs 79 [25%] of 321, adjusted percentage difference 11·5% [97·5% CI 4·7-18·3], p=0·0003; ARCADIA 2: 197 [38%] of 522 vs 69 [26%] of 265, adjusted difference 12·2% [4·6-19·8], p=0·0006) and an EASI-75 response (ARCADIA 1: 270 [44%] vs 93 [29%], adjusted difference 14·9% [7·8-22·0], p<0·0001; ARCADIA 2: 220 [42%] vs 80 [30%], adjusted difference 12·5% [4·6-20·3], p=0·0006). Significant benefits were observed with nemolizumab for all key secondary endpoints including improvement in itch, as early as week 1, and sleep improvement by week 16. The safety profile was similar between nemolizumab plus TCS-TCI and placebo plus TCS-TCI. In the safety sets, 306 (50%) of 616 participants (ARCADIA 1) and 215 (41%) of 519 participants (ARCADIA 2) who received nemolizumab plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in six [1%] and 13 [3%], respectively); and 146 (45%) of 321 (ARCADIA 1) and 117 (44%) of 263 (ARCADIA 2) who received placebo plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in four [1%] and three [1%], respectively). Ten serious treatment-emergent adverse events possibly related to nemolizumab were reported in five (1%) participants in ARCADIA 2. No deaths occurred. Nemolizumab plus TCS-TCI was efficacious and showed statistically and clinically significant improvements in inflammation and itch in adults and adolescents with moderate-to-severe atopic dermatitis. Nemolizumab might offer a valuable extension of current therapies if approved. Galderma.

Predicting Abrocitinib Efficacy at Week 12 Based on Clinical Response at Week 4: A Post Hoc Analysis of Four Randomized Studies in Moderate-to-Severe Atopic Dermatitis.

Early prediction of abrocitinib efficacy in atopic dermatitis (AD) could help identify candidates for an early dose increase. A predictive model determined week 12 efficacy based on week 4 responses in patients receiving abrocitinib 100mg/day and assessed the effect of an abrocitinib dose increase on platelet counts. Analysis included the phase 3 trials JADE MONO-1 (NCT03349060), MONO-2 (NCT03575871), COMPARE (NCT03720470), and TEEN (NCT03796676). For platelet counts and simulations, a phase 2 psoriasis trial (NCT02201524) and phase 2b (NCT02780167) and phase 3 (MONO-1, MONO-2, and REGIMEN (NCT03627767)) abrocitinib trials were pooled. A training-and-validation framework assessed potential predictors of response at week 4: score and score change from baseline in the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), and Peak Pruritus Numerical Rating Scale (PP-NRS), and percentage change from baseline in EASI. The dependent variables at week 12 were ≥ 75% improvement in EASI (EASI-75) and IGA score of 0 (clear) or 1 (almost clear) and ≥ 2-point improvement from baseline. The probability of each variable to predict week 12 EASI-75 and IGA responses was calculated. In the training cohort (n = 453), 72% of the ≥ 50% improvement in EASI (EASI-50) at week 4 responders and 16% of the nonresponders with abrocitinib 100mg achieved EASI-75 at week 12; 48% and 6% of the week 4 EASI-50 responders and nonresponders, respectively, achieved week 12 IGA response. Similar results occurred with week 4 IGA = 2, ≥ 4-point improvement from baseline in PP-NRS, or EASI = 8 responders/nonresponders. Platelet counts after an abrocitinib dose increase from 100 to 200mg were similar to those seen with continuous dosing with abrocitinib 100mg or 200mg. Achieving week 4 clinical responses with abrocitinib 100mg may be useful in predicting week 12 responses. Week 4 nonresponders may benefit from a dose increase to abrocitinib 200mg, and those that receive this dose increase are likely to achieve treatment success at week 12, with no significant impact on platelet count recovery. Video abstract available for this article. NCT03349060, NCT03575871, NCT03720470, NCT03796676, NCT02201524, NCT02780167 and NCT03627767.

Efficacy and Safety of Abrocitinib in Prurigo Nodularis and Chronic Pruritus of Unknown Origin

Prurigo nodularis (PN) and chronic pruritus of unknown origin (CPUO) are chronic pruritic diseases that dramatically impair quality of life, but therapeutic options are limited. Abrocitinib, a Janus kinase 1 inhibitor, represents a promising therapy for both conditions. To assess the efficacy and safety of 200-mg oral abrocitinib administered once daily in adults with moderate to severe PN or CPUO. This phase 2, open-label, nonrandomized controlled trial conducted between September 2021 and July 2022 took place at a single center in the US. A total of 25 adult patients with moderate to severe PN or CPUO were screened. Ten patients with PN and 10 patients with CPUO were enrolled. All 20 patients completed the 12-week treatment period, 18 of whom completed the 4-week follow-up period. Abrocitinib, 200 mg, by mouth once daily for 12 weeks. The primary efficacy end point was the percent change in weekly Peak Pruritus Numerical Rating Scale (PP-NRS) scores from baseline to week 12. Key secondary end points included the percentage of patients achieving at least a 4-point reduction in weekly PP-NRS score from baseline to week 12 and the percent change in Dermatology Life Quality Index (DLQI) scores. A total of 10 patients with PN (mean [SD] age, 58.6 [13.1] years; all were female) and 10 patients with CPUO (mean [SD] age, 70.7 [5.6] years; 2 were female) enrolled in the study. The mean (SD) baseline PP-NRS score was 9.2 (1.0) for PN and 8.2 (1.2) for CPUO. PP-NRS scores decreased by 78.3% in PN (95% CI, -118.5 to -38.1; P < .001) and 53.7% in CPUO (95% CI, -98.8 to -8.6; P = .01) by week 12. From baseline to week 12, 8 of 10 patients with PN and 6 of 10 patients with CPUO achieved at least a 4-point improvement on the PP-NRS. Both groups experienced significant improvement in quality of life as demonstrated by percent change in DLQI scores (PN: -53.2% [95% CI, -75.3% to -31.1%]; P = .002; CPUO: -49.0% [95% CI, -89.6% to -8.0%]; P = .02). The most common adverse event among patients was acneiform eruption in 2 of 20 patients (10%). No serious adverse events occurred. The results of this nonrandomized controlled trial suggest that abrocitinib monotherapy may be effective and tolerated well in adults with PN or CPUO. Randomized, double-blind, placebo-controlled trials are warranted to validate these findings. ClinicalTrials.gov Identifier: NCT05038982.

Efficacy and Safety of Dupilumab in Chinese Elderly Patients with Atopic Dermatitis: A Real-World Study

Introduction: With the aging of the population in China, the prevalence of atopic dermatitis (AD) is high in elderly patients. These patients usually have more comorbidities and they need more effective and safer treatments. Dupilumab is an anti-interleukin-4 (IL-4) receptor monoclonal antibody which was approved for the treatment of moderate-to-severe AD. Methods: Elderly patients (60 years or older) with moderate-to-severe AD who treated with dupilumab were included. Eczema Area and Severity Index (EASI) score, Peak Pruritus Numerical Rating Scale (PP-NRS), EASI-50, EASI-75, and EASI-50 were evaluated. The efficacy in subgroups was also investigated. Results: Fifty-eight patients were enrolled. The EASI score and PP-NRS score were significantly reduced at weeks 4, 16, 28, and 52. 91.2% and 79.4% of the patients achieved EASI-50 and EASI-75 at week 16, respectively. 95.8% and 87.5% patients achieved EASI-50 and EASI-75 at week 52, respectively. Adverse events were reported in 10 (17.2%) patients, and no severe adverse event was reported. Male, older age, and moderate AD (EASI <21) were related to better efficacy. Conclusions: This study demonstrated that dupilumab is effective and safe in elderly patients with AD.

Abrocitinib may improve itch and quality of life in patients with itch-dominant atopic dermatitis.

Patients with atopic dermatitis (AD) exhibit heterogeneous clinical phenotypes, reflecting different combinations of itch and lesional severity. AD with severe itch but clear-moderate lesions, also known as itch-dominant AD, is a common clinical phenotype. To evaluate abrocitinib efficacy in patients with moderate-to-severe AD who have itch-dominant AD. This post hoc analysis includes pooled data from clinical trials of patients with moderate-to-severe AD receiving abrocitinib (100 or 200mg) as monotherapy (phase 2b; phase 3 JADE MONO-1 and JADE MONO-2) or in combination with topical therapy (phase 3 JADE COMPARE). Data from the ongoing long-term JADE EXTEND trial (data cutoff April 2020) were also evaluated. Itch-dominant AD was defined as baseline Peak Pruritus Numerical Rating Scale (PP-NRS) score of 7-10 and Investigator's Global Assessment of 0-3 or Eczema Area and Severity Index of 0‒21. Assessments included a ≥4-point improvement in PP-NRS (PP-NRS4), PP-NRS score of 0 (no itch) or 1 (little itch) in patients with PP-NRS score ≥2 at baseline, ≥4-point improvement from baseline in Patient-Oriented Eczema Measure (POEM-4), Patient Global Assessment (PtGA) of clear or almost clear, and Dermatology Life Quality Index (DLQI) score of 0 or 1 (no impact or little impact of AD on quality of life [QoL]). In the pooled monotherapy trials, 37% of patients had itch-dominant AD at baseline. As early as Week 2, more patients with itch-dominant AD achieved PP-NRS4 with abrocitinib 100mg (35%) and abrocitinib 200mg (57%) versus placebo (7%); 6% and 22% versus 0%, respectively, achieved PP-NRS 0/1. More patients achieved a PtGA of clear/almost clear at Week 12 with abrocitinib 100mg (28%) and abrocitinib 200mg (45%) than placebo (9%). Additionally, abrocitinib led to clinically meaningful improvements in POEM and DLQI. Most patients with itch-dominant AD experienced itch improvement over time with abrocitinib monotherapy or with concomitant topical therapy; 86%-87% and 62%-67% of patients had no itch-moderate itch and clear-moderate lesions by weeks 24 and 48, respectively. Abrocitinib is highly efficacious in patients with itch-dominant AD, demonstrating rapid, deep, and sustained improvements in itch and clinically meaningful improvements in patients' QoL. NCT02780167; NCT03349060; NCT03575871; NCT03720470; NCT03422822.

Efficacy and Safety of Crisaborole Ointment 2% in Chinese Patients Aged ≥ 2 Years with Mild to Moderate Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic immuno-inflammatory skin disease. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild to moderate AD. This post hoc analysis assesses the efficacy and safety of crisaborole in Chinese patients aged ≥ 2years with mild to moderate AD. We evaluated the efficacy and safety of crisaborole in Chinese patients from the vehicle-controlled, phase 3 CrisADe CLEAR study. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily, respectively, for 28days. The primary endpoint was percent change from baseline in Eczema Area and Severity Index (EASI) total score at day 29. Key secondary endpoints were improvement in Investigator's Static Global Assessment (ISGA), ISGA success, and change from baseline in weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score. Adverse events were documented. Of 391 patients in the overall study, 237 were from China, 157 assigned to crisaborole and 80 assigned to vehicle. A greater reduction in percent change from baseline in EASI total score at day 29 was shown in the crisaborole vs. vehicle group (least squares mean [LSM]: -66.34 [95% (confidence interval) CI -71.55 to -61.12] vs. -50.18 [95% CI -58.02 to -42.34]). Response rates for achievement of ISGA improvement (43.2% [95% CI 35.4-51.1] vs. 33.4% [95% CI 22.5-44.2]) and ISGA success (31.7% [95% CI 24.3-39.0] vs. 21.5% [95% CI 12.1-30.9]) at day 29 were higher in the crisaborole vs. vehicle group. A greater reduction in change from baseline in weekly average PP-NRS score at week 4 was observed in the crisaborole vs. vehicle group (LSM: -1.98 [95% CI -2.34 to -1.62] vs. -1.08 [95% CI -1.63 to -0.53]). No new safety signals were observed. Crisaborole was effective and well tolerated in Chinese patients aged ≥ 2years with mild to moderate AD. ClinicalTrials.gov, NCT04360187.