Pruritus Numerical Rating Scale Research Articles

Improvement Across Dimensions of Disease with Lebrikizumab Use in Atopic Dermatitis: Two Phase 3, Randomized, Double-Blind, Placebo-Controlled Monotherapy Trials (ADvocate1 and ADvocate2).

Atopic dermatitis is a complex, chronic, inflammatory skin disease thatrequires long-term control of symptoms like itch and sleep loss and improvement in quality of life, in addition to reduction of clinical signs. Lebrikizumab is a selective interleukin-13 inhibitor approved in the European Union, United Kingdom, United Arab Emirates, Canada, and Japan for treatment of moderate-to-severe atopic dermatitis in adults and adolescents. Here, we assess the magnitude of changes across signs and symptoms of atopic dermatitis with lebrikizumab monotherapy over the 16-week induction period in two phase 3 studies, ADvocate1 and ADvocate2. Eligible adults (aged≥18years) and adolescents (aged 12 to<18years and weighing≥40kg) with moderate-to-severe atopic dermatitis were randomized to receive either 250mg of lebrikizumab or placebo subcutaneously every two weeks. Least squares mean percentage change from baseline through week 16 was compared between lebrikizumab and placebo using mixed model repeated measure analysis for the following endpoints: Eczema Area and Severity Index (EASI), Pruritus Numeric Rating Scale (NRS), Sleep-Loss Scale, Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). In both trials, significant (P<0.05) improvements were observed for lebrikizumab treatment compared with placebo at each 2-week timepoint for EASI, Pruritus NRS, Sleep-Loss Scale, and POEM, and at each 4-week timepoint for DLQI, through week 16. Statistically significant (P<0.001) improvements were observed at 16weeks for lebrikizumab treatment versus placebo in ADvocate1/ADvocate2 for EASI (71.9%/75.0% vs. 35.6%/43.3%), Pruritus NRS (53.3%/46.3% vs. 21.4%/18.0%), Sleep-Loss Scale (57.7%/55.6% vs. 23.9%/25.5%), POEM (54.4%/45.8% vs. 18.8%/16.9%), and DLQI (64.2%/60.5% vs. 28.5%/32.2%). Patient photos show improvements in skin appearance when disease measures improve. Lebrikizumab monotherapy resulted in significant and fast improvements in multiple dimensions of disease (clinical signs, symptoms, and quality of life) over 16weeks in patients with moderate-to-severe atopic dermatitis. ClinicalTrials.gov identifiers, NCT04146363; NCT04178967.

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.

More Time Spent with Clear Skin and No Itch with Upadacitinib versus Dupilumab for Atopic Dermatitis.

Atopic dermatitis (AD), with its hallmark symptoms of pruritus and skin lesions, often impairs patients' quality of life. We assessed time spent with clear/almost clear skin and no/minimal itch during upadacitinib treatment versus placebo or dupilumab among patients with moderate-to-severe AD. This analysis consisted of a post hoc analysis of Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 were replicate, randomized, double-blind, placebo-controlled phase 3 studies with patients randomized (1:1:1) to once-daily oral upadacitinib 15mg, upadacitinib 30mg, or placebo for 16weeks. Heads Up was a head-to-head, randomized, double-blind, double-dummy, phase 3b study with patients randomized (1:1) to upadacitinib 30mg or subcutaneous dupilumab 300mg for 24weeks. Skin clearance was assessed with the Eczema Area and Severity Index (EASI) at baseline, weeks 1, 2, and 4, and every 4weeks thereafter. Itch was assessed using the Worst Pruritus Numerical Rating Scale (WP-NRS) daily over 16weeks and every 2weeks thereafter to week 24 in Heads Up. This analysis included 1683 patients in Measure Up 1 and 2 and 673 patients in Heads Up. Through 16weeks in Measure Up 1 and 2, patients receiving upadacitinib spent 9.8-13.4 times as many days with an EASI 90 response and 7.0-10.3 times as many days with a WP-NRS 0/1 response versus placebo. In Heads Up, patients receiving upadacitinib spent 2.0 and 1.7 times as many days through 16 and 24weeks, respectively, with an EASI 90 response versus dupilumab. Through 16 and 24weeks, patients receiving upadacitinib spent 3.0 and 2.6 times as many days, respectively, with a WP-NRS 0/1 response versus dupilumab. Patients with moderate-to-severe AD spent more time with clear/almost clear skin and no/minimal itch with upadacitinib versus placebo or dupilumab. ClinicalTrials.gov identifier, Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), Heads Up (NCT03738397).

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.

Efficacy of Upadacitinib and Dupilumab on Achieving Stringent and Composite Skin and Itch Outcomes: an Indirect Comparison of Adults with Moderate-to-Severe Atopic Dermatitis.

Efficacy of upadacitinib has been assessed in trials including Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and Heads Up (NCT03738397). Measure Up 1 and 2 assessed efficacy of upadacitinib 30mg and upadacitinib 15mg against placebo, while Heads Up assessed efficacy of upadacitinib 30mg in a head-to-head trial against dupilumab 300mg. A head-to-head trial of upadacitinib 15mg against dupilumab 300mg has not been conducted. Network meta-analysis has shown that upadacitinib 30mg and upadacitinib 15mg are among the most efficacious targeted systemic therapies, but prior indirect comparisons have not evaluated more stringent outcomes. A population-adjusted indirect comparison was conducted using post hoc individual patient data from Measure Up 1 and 2 and Heads Up to estimate how upadacitinib 15mg would have performed if included in Heads Up by adjusting for patient-level covariates. Absolute response rates at weeks 4, 16, and 24 were estimated for the following outcomes: no/minimal itch [Worst Pruritus Numerical Rating Scale (WP-NRS) score of 0/1], Eczema Area and Severity Index (EASI) score of ≤ 3 (EASI ≤ 3), 100% improvement in EASI (EASI 100), both ≥ 90% improvement in EASI (EASI 90) and WP-NRS 0/1, both EASI ≤ 3 and WP-NRS 0/1, and both EASI 100 and WP-NRS 0/1. The analysis was conducted on adult patients, aligned with the intention-to treat population for the clinical trials, and used non-responder imputation. Across all outcomes assessed, the estimated absolute response rates were greatest for upadacitinib 30mg, followed by upadacitinib 15mg and then dupilumab. This pattern was observed at week 4, week 16, and week 24. For adults with moderate-to-severe AD, upadacitinib 30mg appears to be the most efficacious treatment in attaining more stringent and composite outcomes across multiple timepoints, followed by upadacitinib 15mg and then dupilumab 300mg.

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.

Dupilumab in Patients with Atopic Dermatitis: A Multicentric, Long-Term, Real-World Portuguese Study.

Several clinical trials have established the efficacy and safety of dupilumab for treating atopic dermatitis (AD). However, literature remains scarce in reporting the long-term effectiveness, safety, and drug survival of dupilumab in real-world settings. This study aimed to describe the latter outcomes of dupilumab in patients with AD. This Portuguese, multicentric, observational, retrospective study included consecutive adult patients with AD who initiated dupilumab between January 2019 and September 2023, with a follow-up period up to 30months. Drug discontinuation and adverse effects data were used to estimate drug survival. Clinical assessments included the Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), and Dermatology Life Quality Index (DLQI). A total of 312 patients were included in the study, with 56.4% being male (median age of 30years, range 18-83). The 30-month drug survival rate was 82.0%. During the study period, 12.5% of the sample (n = 39 patients) discontinued treatment: 7.3% due to treatment failure, 2.9% due to safety concerns, 1.3% due to complete disease control, 0.6% due to pregnancy, and 0.3% due to lack of compliance. Adverse events not leading to drug discontinuation were noted in 25.6% of the sample (n = 80). Conjunctivitis was the most frequently reported adverse event (17%), followed by facial erythema (9%). At 30months, the mean EASI decreased significantly from 27.30 ± 11.89 at baseline to 2.92 ± 3.96 (p < 0.001), reflecting an overall improvement of 89.3%. Similarly, pruritus NRS decreased from 7.36 ± 1.90 at baseline to 1.74 ± 2.16 at month 30 (p < 0.001), improving by 76.4%, and mean DLQI changed from 18.0 ± 7.09 at baseline to 2.67 ± 3.95 at month 30 (p < 0.001), decreasing by 85.2%. This study increases our current understanding of dupilumab in real-world settings, demonstrating its long-term effectiveness and safety in treating AD.

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.

Cross-sectional burden-of-illness study in atopic dermatitis (MEASURE-AD) in Australia and New Zealand reveals impacts on well-being.

To describe disease burden in individuals with moderate-to-severe atopic dermatitis (AD) in Australia and New Zealand (ANZ) and compare it with other geographic regions. This multicentre, cross-sectional, observational study (MEASURE-AD) recruited consecutive adolescent and adult patients attending dermatology clinics in 28 countries. Data collected included scores of pruritus, disease severity, sleep, pain, disease control, work and quality of life. This study included 112 ANZ participants (Australia n = 72; New Zealand n = 40) from December 2019 to December 2020. Treatments included topicals (85.7% of patients), non-biologic systemic therapy (28.6%), phototherapy (9.8%) and dupilumab (4.5%). Mean Eczema Area and Severity Index (EASI) score was 22.3 (95% CI 19.6-25.0) and Patient-Oriented Eczema Measurement (POEM) score was 18.4 (95% CI 16.8-20.0). Pruritus Numerical Rating Scale (NRS) was 6.0 (95% CI 5.5-6.6) (50% had severe pruritus) and Dermatology Life Quality Index (DLQI) 14.3 (95% CI 12.8-15.8). ADerm-Impact sleep domain score was 15.1 (95% CI 13.2-16.9). ADerm-Symptom Scale worst skin pain domain score was 5.0 (95% CI 4.3-5.6). Work Productivity and Activity Impairment (WPAI) percentages indicated work and productivity impairment. Inadequately controlled AD was self-reported by 41%, with 9.7 flares in the past 6 months. Scores of pruritus, disease severity, sleep, pain, disease control and quality of life in ANZ were often the highest of all the geographic regions studied. ANZ patients with AD have a high disease burden, which extends across multiple facets of daily life. Many are inadequately controlled with existing therapies.

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 of Janus kinase inhibitors in the treatment of psoriasiform atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disease with multiple clinical manifestations. Among AD phenotypes, psoriasiform AD shows the coexistence of eczematous itching lesions in flexural areas with psoriasiform plaques. The use of anti-interleukin (IL)-4 and anti-IL-13 in psoriasiform AD may lead to therapeutic failure or worsening of manifestations. A recent Delphi consensus proposed Janus kinase inhibitors (JAKi) as a viable alternative, even as a first-line treatment, in patients with different clinical phenotypes of AD, including psoriasiform AD. We performed a retrospective analysis of patients in our dermatology clinic with moderate-to-severe AD who were treated with JAKi. Among 192 patients overall, 21 had psoriasiform AD. We used the Eczema Area and Severity Index (EASI), Pruritus-Numerical Rating Scale and Dermatology Life Quality Index for considering severity scores, and reduction was observed in all 21 patients at week (W) 4, W16 and W24 of treatment. At W16, 81% and 67% achieved EASI-75 and EASI-90, respectively, while at W24 95% of patients achieved EASI-75 and 86% obtained EASI-90. No adverse event led to treatment interruption. This study confirmed the clinical effectiveness of JAKi treatment in adult patients with moderate-to-severe psoriasiform AD, with a good safety profile. These drugs are proposed as the first choice for treating this form of AD, although further studies with larger cohorts are required.

Rapid and sustained improvements in itch and quality of life with upadacitinib plus topical corticosteroids in adults and adolescents with atopic dermatitis: 52-week outcomes from the phase 3 AD Up study

Purpose: Atopic dermatitis (AD) adversely impacts quality of life (QoL). We evaluated the effect of upadacitinib, an oral selective Janus kinase inhibitor approved for moderate-to-severe AD, plus topical corticosteroids (+TCS) on patient-reported outcomes (PROs) over 52 weeks. Materials and methods: In the phase 3 AD Up study (NCT03568318), adults and adolescents with moderate-to-severe AD were randomized 1:1:1 to once-daily upadacitinib 15 mg, 30 mg, or placebo + TCS. Itch, skin pain/symptoms, sleep, QoL, daily activities, emotional state, mental health, and patient impressions of disease severity/improvement/treatment satisfaction were assessed. Results: This analysis included 901 patients. Within 1–2 weeks, PRO improvements were greater with both upadacitinib doses than with placebo (p <.05). Improvements increased through weeks 4–8; rates were generally maintained through week 52. At week 52, the proportion of patients with clinically meaningful improvements in itch (Worst Pruritus Numerical Rating Scale improvement ≥4), skin pain (AD Symptom Scale Skin Pain improvement ≥4), sleep (AD Impact Scale [ADerm-IS] Sleep improvement ≥12), daily activities (ADerm-IS Daily Activities improvement ≥14), and emotional state (ADerm-IS Emotional State improvement ≥11) ranged from 62.1%–77.7% with upadacitinib 15 mg + TCS and 71.3%–83.6% with upadacitinib 30 mg + TCS. Conclusions: Upadacitinib + TCS results in rapid, sustained improvements in burdensome AD symptoms and QoL.

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.

Total eosinophil count as a biomarker for therapeutic effects of upadacitinib in atopic dermatitis over 48 weeks.

Atopic dermatitis (AD) is a chronic skin disease characterized by type 2-skewed immune responses, and significantly influenced by cytokines dependent on Janus kinases (JAKs). Upadacitinib, a JAK1 inhibitor, is effective for moderate-to-severe AD. This study aims to identify biomarkers that reflect long-term therapeutic effects of upadacitinib 15 mg or 30 mg. A retrospective study from August 2021 to July 2023 included 213 AD patients treated with upadacitinib 15 mg and 70 AD patients with 30 mg. We analyzed eczema area and severity index (EASI), peak pruritus-numerical rating scale (PP-NRS), serum immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), and total eosinophil count (TEC) at weeks 0, 4, 12, 24, 36, and 48 of treatment. Both treatments with upadacitinib 15 mg and 30 mg significantly reduced EASI and PP-NRS scores over week 4 to 48 compared to baseline. Upadacitinib 15 mg or 30 mg treatment significantly decreased TEC compared to baseline through week 4 to 36 or week 4 to 48, respectively. The percent reduction of TEC correlated with those of EASI and PP-NRS through week 4 to 48 of treatment with upadacitinib 15 mg, or through week 12 to 48 with 30 mg, respectively. After adjusting for % reductions of other laboratory markers, the significance of correlations was preserved at weeks 36 and 48 of 15 mg treatment, while at weeks 4 and 36 of 30 mg treatment. The % reduction of TEC correlated with those of EASI and PP-NRS during upadacitinib treatment, indicating its potential as a biomarker reflecting treatment responses to upadacitinib in AD patients. However, the variability of significant correlation during treatment indicates that further inspection is needed for its usefulness in monitoring responses to upadacitinib treatment for AD.

Lebrikizumab monotherapy impacts on quality of life scores through improved itch and sleep interference in two Phase 3 trials

Background Lebrikizumab improved itch, interference of itch on sleep, and quality of life (QoL) in patients with moderate-to-severe atopic dermatitis (AD), in two Phase 3 trials at 16 weeks compared to placebo. Objectives We assess improvements in itch and sleep interference due to itch and their impact on QoL measurements after treatment. Methods Data were analyzed from ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) in patients with moderate-to-severe AD. QoL was evaluated using Dermatology Life Quality Index (DLQI) at Week 16 in patients (>16 years of age) who were itch responders/non-responders (defined as ≥4-point improvement in Pruritus Numeric Rating Scale) or Sleep-Loss Scale responders/non-responders (defined as ≥2-point improvement in itch interference on sleep). Results In ADvocate1 and ADvocate2, significantly greater proportions of itch responders had a clinically meaningful improvement in measures related to QoL (DLQI scores (0/1), ≤5 DLQI total score and ≥4-point DLQI improvement) compared to itch non-responders. In both studies, a significantly greater proportion of Sleep-Loss Scale responders, reported a DLQI score of (0/1), DLQI total score of ≤5 and DLQI improvement of ≥4 points compared to Sleep-Loss Scale non-responders. Conclusions Improvement in itch and sleep interference due to itch is associated with improvement in the QoL of patients after treatment with lebrikizumab for moderate-to-severe AD. ClinicalTrials.gov registration NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).

Long-term effectiveness and safety of upadacitinib for Japanese patients with moderate-to-severe atopic dermatitis: a real-world clinical study

Background Previous clinical trials presented efficacy and safety of Janus kinase 1 inhibitor upadacitinib through 52 weeks for moderate-to-severe atopic dermatitis (AD). Objectives To assess the effectiveness and safety of upadacitinib through 48 weeks in real-world clinical practice for Japanese AD patients (aged ≥12 years). Methods This retrospective study included 287 patients with moderate-to severe AD treated with 15 mg (n = 216) or 30 mg (n = 71) of upadacitinib daily. Effectiveness was assessed using eczema area severity index (EASI) scores, atopic dermatitis control tool (ADCT), peak pruritus-numerical rating scale (PP-NRS), and investigator’s global assessment (IGA). Safety was evaluated through the incidence of treatment-emergent adverse events. Results From baseline, EASI, ADCT, PP-NRS, and IGA rapidly reduced at week 4, and the reduction was maintained until week 48 of treatment with upadacitinib at both doses. Achievement rates of EASI 75, EASI 90, and EASI 100 at week 48 were 63.5, 30.2, and 7.9 in 15 mg group, and 77.4, 54.8, and 3.2% in 30 mg group, respectively. Acne and herpes zoster were frequent, but no serious adverse events occurred. Conclusions Upadacitinib was therapeutically effective and tolerable for moderate-to-severe AD through 48 weeks in real-world clinical practice.