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Background: 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., Methods: 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)., Findings: 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., Interpretation: 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., Funding: Galderma., Competing Interests: Declaration of interests JIS has received honoraria as a consultant or advisory board member for AbbVie, Aldena, Amgen, AOBiome, Arcutis, Arena, Asana, Aslan, Attovia, BiomX, Biosion, Bodewell, Boehringer-Ingelheim, Bristol Myers Squibb, Cara, Castle Biosciences, Celgene, Connect Biopharma, Corevitas, Dermavant, Eli Lilly, Galderma, GSK, Incyte, Kiniksa, LEO Pharma, MyOr Diagnostics, Nektar, Novartis, Optum, Pfizer, RAPT Therapeutics, Recludix, Regeneron, Sanofi-Genzyme, Shaperon, Target RWE, and Union Therapeutics; and his institution has received grants from Galderma, Incyte, and Pfizer. AW has received grants or contracts from AbbVie, Aileens, Almirall, Amgen, Beiersdorf, Bioderma, BioProject, Bristol Myers Squibb, Chugai, Galapagos, Galderma, Glenmark, GSK, Hans Karrer, Janssen, Maruho, MedImmune, MSD, Mylan, Novartis, Pfizer, Pierre Fabre, Regeneron, Sandoz, Sanofi-Aventis, and UCB; payment or honoraria from AbbVie, Aileens, Almirall, Amgen, Beiersdorf, Bioderma, Galderma, Glenmark, LEO Pharma, L'Oreal, Maruho, Novartis, Pfizer, Pierre Fabre, Regeneron, Sanofi-Aventis, and UCB; and support for attending meetings or travel from AbbVie, LEO Pharma, and Pierre Fabre. He has also participated on a data safety monitoring board or advisory board for Alentis Therapeutics and BioProject; served as Secretary and Executive Board member of the International Society of Atopic Dermatitis and Vice Chair of the European Task Force on Atopic Dermatitis; and received medical writing support for clinical trial reports from AbbVie, Almirall, Galderma, LEO Pharma, Eli Lilly, L'Oreal, Merck, Novartis, Pfizer, Pierre Fabre, Regeneron, Sanofi-Aventis, and UCB. AR has served as an investigator or participated in advisory boards for AbbVie, Alvotech, Amgen, AnaptysBio, Biotherapy, Bristol Myers Squibb, Celgene, Celltrion, Dermira, Galderma, Inflarx, Janssen, Kiniksa, Kymab, LEO Pharma, Novartis, Pierre Fabre, Pfizer, Trevi Therapeutics, and UCB; and has received honoraria from Chema Rzeszow, Eli Lilly, LEO Pharma, Novartis, Sandoz, and Takeda. DT is a lecturer or consultant for AbbVie, Almirall, Amgen, Boehringer-Ingelheim, Bristol Myers Squibb, Celltrion, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Eli Lilly, Novartis, Regeneron, Sandoz, Target RWE, and UCB; and has received grants from AbbVie, LEO Pharma, and Novartis (paid to his institution). FJL has received honoraria as a consultant, advisory board member, or speaker for Almirall, Celgene, Eli Lilly, Galderma, Menlo Therapeutics, Novartis, Pelpharma, Pfizer, Sanofi, Trevi Therapeutics, and Vifor Pharma; has received support for participating in scientific meetings from Amgen, AbbVie, Celgene, Eli Lilly, Galderma, Janssen-Cilag, LEO Pharma, Novartis, Pelpharma, Pfizer, and Sanofi; and has served as the principal investigator in clinical studies for Amgen, Almirall, DS Biopharma, Eli Lilly, Galderma, Incyte, Kiniksa, Menlo Therapeutics, LEO Pharma, Pfizer, and Trevi Therapeutics. KAP has served as a consultant, scientific advisor, investigator, scientific officer, or speaker for Pfizer, AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite BioPharma, Celltrion, Concert Pharmaceuticals, CorEvitas, Dermavant, Dermira, Dice Pharmaceuticals, Dice Therapeutics, Eli Lilly, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte, Janssen, Kymab, Kyowa Hakka Kirin, LEO Pharma, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Reistone, Sandoz, Genzyme (subsidiary of Sanofi Aventis), Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB, and Zai Lab. LSG has received grants, contracts, consulting fees, payment, or honoraria for scientific or educational work from Galderma, AbbVie, Pfizer, Incyte, Arcutis, LEO Pharma, Dermavan, and Eli Lilly; and is an investigator for Allergan and Galderma. J-DB has received speaker fees from AbbVie, AstraZeneca, Galderma, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, and Sanofi, consulting fees from Eli Lilly and Neovacs, a research grant from Astra Zeneca, Sanofi, and Therakos, and travel grants from AbbVie, Janssen, and Sanofi; and has served on a data safety monitoring board or advisory board for AbbVie, AstraZeneca, Galderma, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, and Sanofi. AEP has received grants or contracts from Amgen, Medac Pharma, and Pfizer, acted as an investigator, speaker, and advisor for or received educational support or research funding from Sanofi, Eli Lilly, Pfizer, LEO Pharma, AbbVie, Galderma, Novartis, Janssen, Boehringer Ingelheim, Bristol Myers Squibb, UCB, Amgen, Almirall, Artax Biopharma, and Medac Pharma. JMC has received honoraria as a consultant, advisory board member, or speaker, or has served as the principal investigator in clinical studies, for Almirall, Celgene, Eli Lilly, Galderma, Novartis, Pfizer, Sanofi, Amgen, AbbVie, Janssen-Cilag, LEO Pharma, UCB, Boehringer Ingelheim, Bristol Myers Squibb, and Sandoz. BR has served as an investigator for Galderma. JCS has received consulting fees or honoraria from Galderma, AbbVie, Almirall, Eli Lilly, Janssen, LEO Pharma, Novartis, Pierre-Fabre, Pfizer, Sanofi-Genzyme, Trevi, and UCB; has served as President of the Polish Dermatological Society; and has served as an investigator for AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InflaRx, Janssen, Kliniksa, Kymab, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Trevi Therapeutics, and UCB Pharma. DK has served as an investigator for Galderma. BH is an investigator for Galderma. MK has served as an investigator for Galderma. NM is a consultant or speaker for AbbVie, Almirall, Apogee, Boehringer Ingelheim, Bristol Myers Squibb, Dr Wolff, Eli Lilly, La Roche-Posay, LEO Pharma, Novartis, Pfizer, Sanofi, and UCB; and has served as an investigator for Galderma. SP has served as an investigator for Galderma. NN has served as an investigator for Galderma. MBS has received honoraria as a consultant, advisory board member, or speaker from Amgen, AbbVie, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Galderma, Incyte Pharma, Janssen, L'Oréal Canada, LEO Pharma, Merck, Novartis, Pfizer, Sanofi, Sun Pharmaceuticals, and UCB Canada; support for attending meetings or travel from Galderma, Janssen, and Pfizer; has served as the principal investigator in clinical studies for Alumis, Amgen, AbbVie, Bristol Myers Squibb, Dermavant, Evelo, Galderma, Inycte, Janssen, LEO Pharma, Meiji Pharma, Moberg Pharma, Novartis, Pfizer, Reistone Biopharma, Sanofi, and Ventyx Biosciences; and is Treasurer for the Canadian Dermatology Association, Treasurer for the Ontario Medical Association section of Dermatology, and Secretary for the Dermatology Association of Ontario. VJ has consulted or advised for or received research funding for speakers bureaus from Pediapharm, Aralez, Sanofi, Regeneron, Bausch, Novartis, Medexus, ALK-Abelló, Celgene, LEO Pharma, Mylan, Amgen, AbbVie, Pfizer, AstraZeneca, GSK, Covis Pharma, and Incyte; and has received research grants from Eli Lilly, Pfizer, Galderma, AstraZeneca, Arcutis, Sanofi, LEO Pharma, Amgen, AbbVie, GSK, Allakos, Novartis, Janssen, and Kymab. KP has served as an investigator for Galderma. SYC, PFM, LU, and CP are employees of Galderma., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: In patients with moderate-to-severe atopic Dermatitis® (AD), greater skin clearance and itch reduction are associated with more pronounced improvements in quality of life (QoL). Objective : To characterize the aggregate response benefit with upadacitinib versus dupilumab or placebo in patients with moderate-to-severe AD. Methods : Degree of skin clearance and itch response in 3 phase 3 studies (Heads Up [NCT03738397] and Measure Up 1/2 [integrated; NCT03569293/NCT03607422]) were assessed by the Eczema Area and Severity Index (EASI) and Worst Pruritus Numerical Rating Scale (WP-NRS), respectively, using mutually exclusive categories. The aggregate response benefit with upadacitinib over dupilumab or placebo was determined by summing incremental differences for each EASI or WP-NRS category across the full distribution of patient responses. Results : Comparisons across EASI improvement threshold distributions, EASI severity levels, and WP-NRS categories demonstrated an aggregate response benefit favoring upadacitinib over dupilumab as early as week 4 and continuing at weeks 16 and 24. Similar trends were observed for upadacitinib 15 and 30 mg versus placebo. Conclusions : The aggregate response benefit in skin clearance and itch reduction favored upadacitinib 30 mg over dupilumab and upadacitinib 15 or 30 mg over placebo. These benefits may translate to overall greater improvements in patient QoL.

Background: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis., Objective: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis., Methods: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16., Results: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes., Conclusions: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52., Clinical Trial Registration: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018)., (© 2024. The Author(s).)

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, skin pain, and sleep impacts, which are only reportable by patients themselves. The goal of this research is to evaluate the reliability, validity, and interpretability of the scores from three patient-reported outcome measures within the context of a clinical trial for adolescents and adults with moderate to severe AD., Methods: Data from a Phase 3 randomized, double-blind, placebo-controlled, multinational clinical trial for individuals 12-75 years of age with moderate to severe AD (AD Up [ClinicalTrials.gov NCT03568318]) were used to assess the reliability, validity, and interpretability of scores on the Worst Pruritus Numerical Rating Scale (NRS) and the Atopic Dermatitis Symptom and Impact Scales (ADerm-SS and ADerm-IS). Analyses were conducted separately for the adult and adolescent subgroups., Results: Of the 882 participants included in the psychometric analyses, the majority were adults ( n  = 769, 87.2%), male ( n  = 536, 60.8%), and white ( n  = 630, 71.4%). Multi-item scores from the ADerm-SS and ADerm-IS had good internal consistency reliability, and most scores demonstrated acceptable test-retest reliability. Scores from the three questionnaires demonstrated adequate validity, exhibiting correlations with other conceptually related outcome assessments and score differences between clinically distinct subgroups. Finally, the score interpretation analyses provide estimates for meaningful within-person change and between-groups difference thresholds that may be useful for future research in adults and adolescents with moderate to severe AD., Conclusions: These results provide evidence that the scores produced by the Worst Pruritus NRS, ADerm-SS, and ADerm-IS are reliable and construct-valid when completed by adults and adolescents with moderate to severe AD in a clinical trial setting. The results presented here expand upon the previous qualitative evidence of these tools and provide further support for their use in future clinical studies. While results are specific to clinical trials, next steps would be to evaluate the use of these questionnaires in clinical practice. This can provide clinicians and dermatologists a window into the patient's disease experience outside of the clinic, aid in shared decision making, and support a patient-centric approach to management of moderate to severe AD.

Itch is a complex symptom that is both common and burdensome in atopic dermatitis (AD). Yet, little is known about the longitudinal course of itch in AD. A prospective, dermatology practice-based study was performed of adults with AD (n = 463). Patients were assessed at baseline and approximately 6, 12, 18 and 24 months. Itch was assessed using Numeric Rating Scale (NRS) average and worst-itch scores, and frequency of itch in the past week. Repeated-measures regression models were constructed to examine itch over time. Overall, 31.5% and 22.5% had moderate (4-6) or severe (7-10) NRS average-itch scores; 27.4% and 36.4% had moderate (4-6) or severe (7-10) NRS worst-itch scores; 12.7% and 62.0% had itch from eczema 3-4 and ≥ 5 days in the past week; 27.4% and 45.1% reported sometimes and often/almost always having itch, respectively. Among patients with baseline moderate (4-6) or severe (7-10) NRS average-itch scores, 21.2% and 16.3% continued to have moderate or severe scores at ≥ 1 follow-up visits. In repeated-measures regression models, persistent NRS average-itch scores were associated with baseline NRS average-itch [adjusted β (95% CI): 0.75 (0.68, 0.82)] and food allergy [- 0.45 (- 0.84, - 0.07)]. Persistent NRS worst-itch was associated with baseline worst-itch NRS [0.73 (0.66, 0.80)] and Medicaid insurance [1.06 (0.17, 1.94)]. AD patients had a heterogeneous longitudinal course with fluctuating and complex overlapping patterns of average- and worst-itch intensity, and frequency., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Itch is a complex and burdensome symptom in atopic dermatitis (AD). Severity of scratching/excoriation (SCORAD-scratch) has been found to be a valid measure of itch in AD. However, little is known about the longitudinal course of scratching/excoriations in AD., Methods: A prospective, dermatology practice-based study was performed of adults with AD (N = 399). The patients were assessed at baseline and approximately 6, 12, 18, and 24 months., Results: Severity of excoriations correlated best with the Numerical Rating Scale-worst itch (Spearman correlation, ρ = 0.50), followed by a Patient-Reported Outcome Measurement Information System Itch Questionnaire-scratching behavior T score (ρ = 0.48), Numerical Rating Scale-average itch (ρ = 0.41), relative frequency of itch (ρ = 0.36), and frequency of itch from eczema (ρ = 0.29, all P < 0.0001). Scratching severity showed good reliability (intraclass correlation coefficient range = 0.62-0.69). Overall, 30.6% and 5.5% had moderate (2) or severe (3) SCORAD-scratch scores. Among patients with baseline moderate (2) or severe (3) SCORAD-scratch scores, 18.9% and 13.6% continued to have moderate or severe scores at 1 or more follow-up visits. In repeated-measures regression models, persistent SCORAD-scratch scores were associated with baseline severity of excoriations (adjusted β [95% confidence interval] = 0.51 [0.37 to 0.65]), Medicaid insurance (-0.35 [-0.65 to -0.04]), and Eczema Area and Severity Index scores (0.03 [0.02 to 0.04])., Conclusions: Adult AD patients had a heterogeneous longitudinal course with fluctuating severity of excoriations., Competing Interests: The authors have no relevant conflicts of interest to declare., (Copyright © 2021 American Contact Dermatitis Society. All Rights Reserved.)

Prurigo nodularis (PN) is a chronic, pruritic, debilitating disease. Previous studies found that chronic pruritus in general negatively affects patients' quality of life (QoL). However, results about the impact of PN on QoL are conflicting. Our objective was to assess the QoL burden of PN. A systematic review was conducted of all published studies that assessed QoL measures in PN. OVID MEDLINE, EMBASE, SCOPUS, and Web of Science were searched. Pooled meta-analysis (means) was performed using random-effects weighting. Overall, 13 studies met inclusion criteria. All studies identified QoL reductions in patients suffering from PN compared to control groups. The most common QoL instrument used was the Dermatology Life Quality Index [n = 9 studies; pooled mean (95% confidence interval): 13.8 (10.6-16.9), denoting a very large effect]. In particular, PN was associated with substantial impact on multiple domains of QoL. No publication bias was detected. In conclusion, QoL is negatively impacted in PN. Future studies are necessary to determine the best instruments of measuring QoL in PN patients, better understand this association, and assess the impact in males and females separately. PROSPERO CRD42019136193., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Atopic dermatitis imparts a substantial patient burden, including itch, sleep disturbance, and decreased health-related quality of life., Objective: This analysis evaluated changes in patient-reported outcomes of disease-specific signs/symptoms and health-related quality of life in adult and adolescent patients with moderate-to-severe atopic dermatitis treated with once-daily oral abrocitinib 200-mg or 100-mg monotherapy., Methods: Pooled data from one phase IIb (NCT02780167) and two phase III (NCT03349060, JADE MONO-1; NCT03575871, JADE MONO-2) monotherapy trials in adult and adolescent patients with moderate-to-severe atopic dermatitis were analyzed. Patient-reported outcome assessments included: global severity, itch, and multi-item measures that assess other signs and symptoms of atopic dermatitis. Additional patient-reported outcome assessments measured depression, anxiety, fatigue, disease-specific and general health-related quality of life, and work and general productivity among employed patients., Results: Overall, 942 patients were included in this analysis. Improvements were observed from the first post-baseline assessment to week 12 across all patient-reported outcomes, including Patient Global Assessment (PtGA) score of 0/1 (35.5%, 19.8%, and 5.9% for 200 mg, 100 mg, and placebo, respectively), ≥ 4-point improvement in Night Time Itch Scale (NTIS; 57.0%, 42.7%, and 12.7%), change from baseline in Patient-Oriented Eczema Measure (POEM) score (- 11.4, - 8.2, and - 3.4), 1-point improvement in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD; 75.2%, 65.1%, and 33.5%), Hospital Anxiety and Depression Scales (HADS) anxiety (- 2.0, - 1.7, and - 1.0) and depression (- 1.7, - 1.3, and - 0.1)., Conclusions: Abrocitinib monotherapy improved disease-specific signs/symptoms and health-related quality of life across multiple domains as reported by adult and adolescent patients with moderate-to-severe atopic dermatitis, complementing clinician-reported efficacy and safety outcomes., Clinical Trial Registration: NCT02780167 (registered 23 May, 2016), NCT03349060 (registered 21 November, 2017), NCT03575871 (registered 3 July, 2018).

Background: Atopic dermatitis (AD) is associated with heterogeneous triggers of itch, which may affect AD course and severity., Objective: To characterize the triggers of itch in adult AD., Methods: This was a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 587). Thirteen itch triggers were assessed using the patient-reported outcomes measurement information system Itch-Triggers., Results: Overall, 381 (64.9%) patients reported greater than or equal to 1 itch trigger in the past week and 212 (36.1%) reported greater than or equal to 3 itch triggers. The most commonly reported triggers were stress (35.4%), sweat (30.5%), weather change (24.7%), dry air (24.4%), and heat (24.0%). In multivariable Poisson regression models, the number of itch triggers was associated with more severe patient-reported global AD severity, Numeric Rating Scale worst itch, Patient-Oriented Eczema Measure, Scoring Atopic Dermatitis sleep, Numeric Rating Scale skin pain, Eczema Area and Severity Index, and objective Scoring Atopic Dermatitis. The seasonality of AD was associated with distinct itch triggers. In multivariable logistic regression models, the number of itch triggers was associated with less than or equal to 3 months of AD remission during the year, greater than or equal to 2 AD flares, and AD being worse during some seasons. Four patterns of itch triggers were identified using latent class analysis, each associated with different clinical characteristics., Conclusion: Itch triggers are common and affect the course of AD. Itch triggers are an important end point to assess in patients with AD., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Skin pain is increasingly recognized as an impactful symptom in atopic dermatitis (AD) because of its association with patient discomfort, disease burden, and reduced quality of life. Although the nature of skin pain in AD has not been systematically studied and is therefore not well understood, patients report soreness, discomfort, and tenderness that may reflect peripheral and central pain sensitization. The high prevalence of skin pain suggests that it is not adequately addressed by current therapies for AD and may be undertreated compared with other symptoms. This review discusses the clinical relevance of skin pain with respect to its experience, pathophysiology, relationship with itch, and treatment implications. Recent studies suggest that skin pain presents as a neuropathic symptom independent from itch and the &ldquo;itch-scratch cycle&rdquo;, and poses a unique burden to patients. Recognition of the significant consequences of skin pain and discomfort should reinforce the need to assess and treat this symptom in patients with moderate-to-severe AD. J Drugs Dermatol. 2020;19(10)921-926. doi:10.36849/JDD.2020.5498.

Background: Pruritus (itch) is a cardinal symptom in atopic dermatitis (AD)., Objective: To evaluate the timing and effect of dupilumab on itch., Methods: Analysis of data from 1505 patients with moderate to severe AD included in 4 randomized controlled studies, treated for up to 52 weeks. Adults received dupilumab 300 mg every 2 weeks or placebo monotherapy (SOLO 1: NCT02277743; SOLO 2: NCT02277769), with concomitant topical corticosteroids (CHRONOS: NCT02260986); adolescents (≥12 to <18 y) were treated with dupilumab monotherapy every 2 weeks (200 mg for baseline weight of <60 kg; 300 mg for baseline weight of ≥60 kg) or placebo (AD ADOL: NCT03054428)., Results: Dupilumab showed significant rapid improvements from baseline in daily Peak Pruritus Numerical Rating Scale scores versus placebo, by day 2 in adults and day 5 in adolescents. At treatment end, dupilumab vs placebo/control had greater least-squares mean percent change from baseline in the weekly average of Peak Pruritus Numerical Rating Scale scores: SOLO -47.5% vs -20.5%; AD-ADOL -47.9% vs -19.0%; CHRONOS -57.3% vs -30.9% (P < .0001 for all)., Limitations: Short duration of monotherapy trials (16 weeks)., Conclusion: Across 4 randomized trials, dupilumab treatment showed rapid and sustained improvements in the magnitude of itch, starting with first dose; responses progressively increased and were sustained through to the end of treatment, up to 1 year., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Current patient-reported outcome measures for itch are limited and may not capture its full impact on health-related quality of life. We sought to develop, calibrate, and validate banks of questions assessing the health-related quality of life impact of itch as part of the Patient-Reported Outcomes Measurement Information System. A systematic process of literature review, content-expert review, qualitative research, testing in a sample of 600 adults, classical test theory methods, and item response theory analyses were applied. Exploratory and confirmatory factor analyses were followed by item response theory model and item fit analyses. Four itch-related item banks were developed: (i) general concerns, (ii) mood and sleep, (iii) clothing and physical activity, and (iv) scratching behavior. Item response theory and expert content review narrowed the item banks to 25, 18, 15, and 5 items, respectively. Validity of the item banks was supported by good convergent and discriminant validity with itch intensity, internal consistency, and no significant floor or ceiling effects. In conclusion, the Patient-Reported Outcomes Measurement Information System Itch Questionnaire banks have excellent measurement properties and efficiently and comprehensively assess the burden of itch., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The Patient-Reported Outcomes Measurement Information System (PROMIS) Itch Questionnaire (PIQ) was recently developed., Objective: To validate PIQ short forms in adults with AD., Methods: Self-administered questionnaires and skin examinations were performed in 239 adults with atopic dermatitis (AD) in a dermatology practice setting., Results: PIQ items had good content validity. PIQ item bank T-scores strongly correlated with each other, moderately correlated with numeric and verbal rating scales for worst or average itch and with itch frequency, moderately to strongly correlated with patient-oriented eczema measure, and weakly to moderately correlated with the Eczema Area and Severity Index and Objective-Scoring AD (Spearman correlations, P < .0001). There were significant and stepwise increases of T-scores for all item banks with increasing patient-reported global severity (Wilcoxon rank sum test, P < .0001). However, there was limited ability to discriminate between the lowest or highest 2 levels of AD or itch severity. Item banks showed good internal consistency (Cronbach α, 0.91-0.95). No differential item functioning was identified by age, sex, race/ethnicity, or educational level. There were floor effects for total scores, particularly in almost clear/mild AD or itch., Limitations: Single-center study., Conclusions: PIQ item bank short forms showed good content and construct validity and are feasible for potential use in clinical trials and practice., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Nemolizumab targets the IL-31 receptor α subunit involved in atopic dermatitis (AD) pathogenesis., Objective: We sought to evaluate a new dosing strategy of nemolizumab in patients with AD., Methods: We performed a 24-week, randomized, double-blind, multicenter study of nemolizumab (10, 30, and 90 mg) subcutaneous injections every 4 weeks versus placebo, with topical corticosteroids in adults with moderate-to-severe AD, severe pruritus, and inadequate control with topical treatment (n = 226). The Eczema Area and Severity Index (EASI), the peak pruritus (PP) numeric rating scale (NRS), and the Investigator's Global Assessment (IGA) were assessed. Standard safety assessments were performed., Results: Nemolizumab improved EASI, IGA, and/or NRS-itch scores, with the 30-mg dose being most effective. Nemolizumab (30 mg) reduced EASI scores versus placebo at week 24 (-68.8% vs -52.1%, P = .016); significant differences were observed by week 8 (P ≤ .01). With significant improvement (P = .028) as early as week 4, IGA 0/1 rates were higher for 30 mg of nemolizumab versus placebo at week 16 (33.3% vs 12.3%, P = .008) but not week 24 because of an increased placebo/topical corticosteroid effect (36.8% vs 21.1%, P = .06). PP-NRS scores were improved for 30 mg of nemolizumab versus placebo at week 16 (-68.6% vs -34.3%, P < .0001) and week 24 (-67.3% vs -35.8%, P < .0001), with a difference by week 1 (P < .001). NRS response rates (≥4-point decrease) were greater for 30 mg of nemolizumab versus placebo at week 16 (P ≤ .001) and week 24 (P ≤ .01). Nemolizumab was safe and well tolerated. The most common adverse events were nasopharyngitis and upper respiratory tract infection., Conclusions: Nemolizumab resulted in rapid and sustained improvements in cutaneous signs of inflammation and pruritus in patients with AD, with maximal efficacy observed at 30 mg. Nemolizumab had an acceptable safety profile., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease with substantial patient and population burdens. A number of comorbid health problems occur in patients with AD, aside from the cutaneous signs and symptoms. This review summarizes recent developments in the burden and comorbidities of AD., Data Sources: Literature review., Study Selections: Nonsystematic., Results: Different aspects of AD, such as chronic pruritus, psychosocial distress, and inflammation, can lead to anxiety, depression, or suicidality. Atopic dermatitis is associated with and may predispose to higher risk of other atopic disorders, including asthma, hay fever, food allergy, and eosinophilic esophagitis. Persons with AD appear to be at higher risk for infectious and cardiovascular risk., Conclusion: Atopic dermatitis is associated with substantial burden and comorbidities. Identifying AD comorbidities is essential for proper disease management and improving overall patient outcomes., (Copyright © 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Itch is common and often debilitating. Itch is best assessed by self-report, often using patient-reported outcome measures (PROMs). Current PROMs for itch are limited and may not capture its full impact on quality of life (QOL)., Objective: We sought to develop a comprehensive conceptual model of itch to improve the understanding of itch for clinicians and to serve as a framework for development of efficient and valid PROMs of itch., Methods: Using mixed methods, including systematic review (n = 491 articles), semi-structured interviews (n = 33 adults with chronic itch with multiple etiologies), and grounded theory using a constant comparative approach, we developed a conceptual model of itch., Results: We found the Wilson and Cleary model to be a reasonable framework for organizing our findings. It includes five primary components: biological and physiological variables, symptom status, functional status, general health perceptions, and QOL. We propose a causal relationship beginning with the biological and physiological driving factors, with direct and indirect impacts of itch and its sequelae, including pain and sleep disturbance. These can impair function, lead to task avoidance, stigma, social life and relationship problems, emotional disturbances, and treatment burden. Together, these sequelae alter one's perceptions of health, QOL, and treatment response., Conclusions: Our conceptual model demonstrates the profound patient-burden of itch and identifies unmet needs in the evaluation and management of itch.

Atopic dermatitis (AD) is a complex and heterogeneous disorder with a profound symptom burden and harmful impact on multiple domains of quality of life (QOL). Many different patient-reported outcome (PRO) measures exist to assess clinical manifestations and QOL impairment in AD, but none comprehensively assess all aspects of the disease. This review addresses the PRO and QOL measures currently used in AD and their properties, strengths, weaknesses, and feasibility for assessing AD in randomized controlled trials and clinical practice. Currently, the patient-oriented eczema measure (POEM) has emerged as a preferred PRO for AD clinical manifestations, though no single instrument has developed as a preferred QOL measure. Validated PRO and QOL measures should be incorporated in all clinical trials of AD and in clinical practice where feasible., (Copyright © 2018 Elsevier Inc. All rights reserved.)

There are currently no simple, standardized, objective assessments of itch for clinical trials and practice. We sought to validate and test the severity of scratching as an objective measure of itch (4-point ordinal scale ranging from 0 [not present] to 3 [very prominent] based on the observation of scratching lesions). We performed a prospective outpatient study using questionnaires and evaluations by a dermatologist in adults with atopic dermatitis (n = 261). Severity of scratching best correlated with patient-reported global atopic dermatitis severity (Kendall τ = 0.336, P < 0.0001), numeric rating scale of itch in the past 24 hours (τ = 0.266, P = 0.0010) and 3 days (τ = 0.296, P < 0.0001). Severity of scratching showed responsiveness over time. Patients experiencing improvement of scratching severity of 1 point or greater had significantly lower itch based on numeric rating scale in the past 3 days (Wilcoxon rank sum test, P = 0.0175), 5-D itch scale (P = 0.0146), and Patient-Oriented Eczema Measure scores (P = 0.0146). There was a significant decrease in scratching severity for patients experiencing itch improvement of 4 points or greater in the past 3 days on the numeric rating scale (Fisher exact test, P = 0.0026), Patient-Oriented Eczema Measure (P < 0.0001), and Dermatology Life Quality Index (P = 0.0285). Severity of scratching may be a useful endpoint in clinical trials and practice across the gamut of pruritic disorders. Future studies are needed to validate severity of scratching in other pruritic disease., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Pruritus occurs in all patients with atopic dermatitis and requires quick relief to reduce disease exacerbation and improve quality of life. Crisaborole ointment is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. This post hoc analysis explores crisaborole ointment for early relief of pruritus in patients with mild to moderate atopic dermatitis from 2 phase III studies. Patients received crisaborole or vehicle twice daily for 28 days. Pruritus was graded on a 4-point scale of none (0) to severe (3). Early improvement in pruritus required a score of none (0) or mild (1), with a ≥ 1-grade improvement from baseline on day 6. Significantly more patients experienced early improvement in pruritus with crisaborole than with vehicle (56.6% vs 39.5%; p< 0.001), including at earliest assessment (day 2, 34.3% vs 27.3%; p = 0.013). Crisaborole is a topical treatment option that can rapidly relieve atopic dermatitis-associated pruritus.

Background: Atopic dermatitis (AD) is associated with itch, skin inflammation and barrier disruption, and scratching, all of which may be associated with skin pain., Objective: To characterize the patient burden of skin pain in AD., Methods: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist., Results: Overall, 305 patients (age range, 13-97 years) were included in the study, with 564 encounters. The cohort included 195 females (63.9%) and 193 whites (63.7%). The mean (SD) age at enrollment was 42.3 (18.1) years, and the mean (SD) age of patient-reported AD onset was 29.6 (31.9) years. At baseline, 144 patients (42.7%) reported skin pain in the past week, with 42 (13.8%) reporting severe or very severe pain. Twenty-four (16.8%) thought the skin pain was part of their itch, 16 (11.2%) from scratching, and 77 (72.0%) from both. Patients with skin pain were more likely to describe their itch using terms that resembled neuropathic pain. Prevalence of skin pain was increased in patients with vs without excoriations (72.6% vs 57.6%; χ 2 test P = .02) but not other morphologic characteristics. Skin pain severity was most strongly correlated with the Patient-Oriented Eczema Measure (Spearman ρ = 0.54), followed by ItchyQOL (ρ = 0.52), 5-dimensions of itch scale (ρ = 0.47), Dermatology Life Quality Index (ρ = 0.45), numeric rating scale for itch (ρ = 0.43) and sleep (ρ = 0.36), Patient Health Questionnaire 9 (ρ = 0.36), patient-reported global AD severity (ρ = 0.34), Eczema Area and Severity Index (ρ = 0.23), and objective Scoring AD index (ρ = 0.20) (P < .001 for all). Patients with both severe itch and pain vs those with only one or neither symptom being severe had significant increases in all these measures., Conclusion: Skin pain is a common and burdensome symptom in AD. Skin pain severity should be assessed with itch severity in AD patients and may be an important end point for monitoring treatment response., (Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Itch is a well-established symptom in cutaneous disease. However, little is known about the burden of itch outside the dermatology setting., Purpose: To determine the prevalence and impact of itch on quality of life (QOL) in the general internal medicine setting., Methods: We performed a cross-sectional study of 2076 adults from an outpatient general internal medicine clinic, using an audio computer-assisted self-administered interview. A history of itch (acute or chronic) and other physical symptoms in the past week, Patient-Reported Outcomes Measurement Information System (PROMIS) 10-item Global Health Questionnaire scores, and Patient Health Questionnaire-2 scores were assessed., Results: The prevalence of itch was 39.9 % and increased with age from 33.1 % at age 19-39 years to 45.9 % at age ≥80 years. In multivariable models controlled for socio-demographics, even feeling "a little" or "some" distress from itch was significantly associated with lower PROMIS global physical and mental health T-scores and estimated health utility scores (P ≤ 0.01). Further, feeling "quite a lot" of distress or "very much" distress from itch was associated with higher adjusted odds ratios for depressed mood (4.91 [95 % confidence interval (CI) 3.36-7.18]) and anhedonia (4.46 [95 % CI 3.07-6.47]). The patient burden of itch was similar to those of pain, constipation, sexual dysfunction, cough, and weight loss., Conclusions: Itch occurs commonly in the primary care setting and is associated with poor QOL. Physicians should inquire about itch and its associations during review of systems. Future studies are needed to distinguish between the effects of acute and chronic itch.

Competing Interests: Conflicts of Interest: None declared.

There are several practice gaps in the evaluation and management of itch. These gaps include a dearth of objective measures of itch, infrequent use of validated patient-reported outcomes for itch, non-evidence-based treatment, and lack of consensus about the ideal workup for generalized itch. The present article reviews these gaps and presents potential solutions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Intense itch associated with atopic dermatitis (AD) can negatively impact sleep. However, the nature of sleep disturbance and fatigue in AD has not been fully elucidated., Objectives: The aim of this study was to determine the burden of sleep disturbance and fatigue in US adults with AD., Methods: This study used a cross-sectional, questionnaire-based survey using a nationally representative sample of 5563 adults from the 2005 to 2006 National Health and Nutrition Examination Survey. Respondents were asked about history of AD, sleep disturbance, and fatigue-related instrumental activity of daily living (IADL) impairment., Results: There was no significant association between having AD and having a diagnosed sleep disorder (10.44% vs 7.27%; odds ratio [OR] [95% confidence interval (CI)], 1.49 [0.84-2.64]; P = 0.23); however, respondents were more likely to report sleep disturbances to clinicians (33.38% vs 23.67%; OR [95% CI], 1.62 [1.10-2.38]; P = 0.04). In multivariate regression models controlling for sociodemographic and lifestyle factors, adults with AD had higher odds of sleep disturbances, including shorter sleep duration (adjusted OR [95% CI], 1.61 [1.16-2.25]), trouble falling asleep (adjusted OR [95% CI], 1.57 [1.10-2.24]), and early morning awakenings (adjusted OR [95% CI], 1.86 [1.24-22.78]). Those with AD also had significantly higher odds of feeling unrested and feeling too tired to perform IADLs., Conclusions: United States adults with AD have significantly impaired sleep and fatigue affecting IADLs, and sleep disturbances may be underdiagnosed in this population.

Objective: To determine whether the extent, distribution, and duration of vitiligo are associated with impairment of specific aspects of quality of life., Design: A prospective questionnaire-based study of 1541 adults with vitiligo., Setting: Online questionnaire., Main Outcome Measures: Affected body surface area (BSA), distribution and duration of vitiligo, associated symptoms, and quality of life using the Dermatology Life Quality Index (DLQI)., Results: Vitiligo had a negative effect on numerous aspects and the total score of the DLQI (mean [SD], 5.9 [5.5]). The DLQI scores in vitiligo were associated with an affected BSA of more than 25% (ordinal logistic regression; adjusted odds ratio, 2.17 [95% CI, 1.71-2.75; P<.001]) and number of body parts affected with vitiligo (P≤.009) but not laterality (P=.06) or duration of disease (P≥.54). Itching and/or burning skin occurred in a sizable percentage of vitiligo patients (35.1%) and were predicted by an affected BSA of more than 25% (adjusted odds ratio, 1.59 [95% CI, 1.26-2.01; P<.001]). Sexual dysfunction occurred in 18% of patients and was predicted by an affected BSA of more than 25% (adjusted odds ratio, 1.94 [95% CI, 1.44-2.61; P<.001]) and vitiligo lesions in the genital area (1.82 [1.30-2.53; P<.001])., Conclusions: Vitiligo extent is associated with increased quality-of-life impairment, including itching and sexual dysfunction. Moreover, different distributions of vitiligo lesions are associated with impairment of different aspects of quality of life., Trial Registration: clinicaltrials.gov Identifier: NCT01401374