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Introduction: Difamilast is the first selective phosphodiesterase 4 inhibitor approved for atopic dermatitis (AD) in Japan. A phase 3, 52-week, open-label study is ongoing to establish efficacy and safety of difamilast ointments in infants with AD aged 3 to < 24 months because a clinical study has not been conducted in this population. Methods: This study consisted of a 4-week primary evaluation period in which difamilast 0.3% ointment was applied twice daily to Japanese infants aged 3 to < 24 months (n = 41) and an ongoing 48-week long-term extension period in which difamilast 0.3% or 1% ointment was applied based on existing symptoms. The data on efficacy and safety of difamilast were obtained as of an interim report in the study period. Results: The response rate in Investigator's Global Assessment score was 45.0% at week 1, which was maintained at 56.1% at week 4 and 63.4% at the interim report. Infants achieved the response rate in Eczema Area and Severity Index 75 (improvement of ≥ 75%) of 47.5% at week 1, which further improved to 82.9% at week 4 and 78.1% at the interim report. Adverse events (AEs) were reported in 22 (53.7%) infants in the primary evaluation period: of those the most frequent AE was nasopharyngitis (19.5%) followed by dermatitis contact (7.3%). As of the interim report, 36 (87.8%) infants experienced AEs: of those, nasopharyngitis (70.7%) and gastroenteritis (22.0%) were most frequently observed. The total AEs were mostly mild or moderate in severity. No investigational medicinal product-related AEs and no AEs leading to discontinuation were reported. Conclusion: Difamilast ointments applied twice daily to Japanese infants with AD aged 3 to < 24 months is effective and well tolerated as of the interim report in the study period. The final results will be reported in the near future. Clinical Trial Registration: Clinical Trials. gov identifier: NCT05372653. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is a chronic relapsing condition with high disease burden and impact on health-related quality of life (HRQoL). Correlations between clinician- and patient-reported outcomes tend to be poor, and limited data in Asian patients are available. Methods: ADDRESS-J was a prospective, non-interventional, longitudinal study that evaluated the real-world effectiveness and safety of AD treatment in Japanese adults (aged 20–59 years) with moderate-to-severe AD. Three clinician-reported AD severity outcomes (Investigator's Global Assessment, Eczema Area and Severity Index, and body surface area affected), three dermatological patient-reported outcomes (Patient-Oriented Eczema Measure, Dermatology Life Quality Index, and Worst Itch Numerical Rating Scale), and two general HRQoL patient-reported outcomes (5-dimension EuroQoL questionnaire and EuroQol Visual Analog Scale) were collected at baseline and every 3 months throughout the 24-month observation period. Four biomarkers were also analyzed when available (thymus and activation-regulated chemokine [TARC], lactate dehydrogenase [LDH], total immunoglobulin E [IgE], and peripheral blood eosinophil counts [PB EOS]). Spearman's correlation coefficients were calculated using all available pooled data from baseline through 24 months. Results: Correlations between the three clinician-reported outcomes were high/very high (Spearman's correlation coefficients 0.76–0.92); those between the three dermatological patient-reported outcomes were moderate (0.53–0.64), and those between the clinician-reported and dermatological patient-reported outcomes were low/moderate (0.37–0.51). Correlations between the general HRQoL patient-reported outcomes and the clinician-reported and dermatological patient-reported outcomes were negligible–moderate (0.26–0.60). Biomarker correlations with the clinician-reported and dermatological patient-reported outcomes were low/moderate for TARC and LDH (0.44–0.63), but negligible/low for PB EOS and total IgE (0.01–0.41). Conclusions: These results show that clinician- and patient-reported outcomes do not necessarily correlate well in Japanese adults with AD. This highlights the importance of including patient-reported outcomes when assessing disease severity/impact, planning treatment, and assessing response to treatment. Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR) Identifier UMIN000022623. Plain Language Summary: Atopic dermatitis (AD) is a long-term recurring skin disease that needs monitoring over time. Various measures (outcomes) are used to assess the severity of AD and its effect on patients. Some outcomes are based on examinations used by clinicians (doctors). Others are based on questionnaires used by patients themselves to report how severe they feel their AD is, and how it affects their lives. It is not known how well these different measures correlate with one another (how a severity score given by one outcome agrees with that given by another outcome), especially in Asian patients. This analysis used information from ADDRESS-J, a study that followed Japanese adults with moderate-to-severe AD who were treated for AD in the real world for a period of 2 years. It used a statistical method to compare three clinician-reported severity outcomes, three dermatological (skin-related) patient-reported outcomes, and two general health-related quality of life patient-reported outcomes. Agreement between the three clinician-reported outcomes was high or very high. Agreement between the three dermatological patient-reported outcomes was moderate. However, importantly, agreement between the clinician-reported outcomes and the dermatological patient-reported outcomes was low or moderate. Agreement between the general health-related quality of life outcomes and all other dermatological outcomes (whether clinician- or patient-reported) was low or moderate. The study showed that clinician-reported and patient-reported AD outcomes do not necessarily agree well in Japanese adults with AD. This highlights the importance of including patient-reported outcomes when evaluating AD, planning treatment, or judging how well patients are responding to treatment. [ABSTRACT FROM AUTHOR]

Introduction: Keloids are a fibroproliferative, multifactorial, cutaneous disorder whose pathophysiology is not completely understood. Various factors such as high blood pressure, pregnancy, female gender, mechanical tension of local sites, and prolonged wound healing are known to worsen keloids. Childhood-onset keloids are keloids that form before 10 years of age, before various factors in adulthood come into play, and thus studying childhood-onset keloids may provide additional insight into the underlying mechanisms that lead to keloid formation. Methods: Retrospective chart review was performed on all patients with childhood-onset keloids who were evaluated at our plastic surgery clinic (one of the largest keloid referral centers in Japan) over a 1-year period. Results: Of the 1443 patients with diagnosis of keloids, 131 patients had childhood-onset keloids. Of these, 106 patients (80.9%) were female, 38.9% of patients had family history of keloids, and 48.9% of patients had allergies or allergy-related conditions (asthma, atopic dermatitis, or allergic rhinitis). Vaccination (47.5%) and chickenpox (19.9%) were the most common triggers. Of vaccinations, BCG was the most common trigger. The majority of keloids from BCG were in female patients (92.9%). The most common location was the chest in male patients (30.0%) and the arm in female patients (41.1%). Conclusion: To our knowledge, this is the largest report in the literature on childhood-onset keloids. There was overall female predominance in childhood-onset keloids, and even more significant female predominance in BCG-induced keloids. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) is an inflammatory disease causing severe skin itching. Data on patient–physician disconnect on treatment satisfaction in patients with AD in Japan are limited. We investigated patient–physician disconnect on treatment satisfaction in AD and if it influences treatment patterns, clinical characteristics, and patient-reported outcomes (PROs). Methods: Data were drawn from the Adelphi AD Disease Specific Programme (DSP), a real-world, point-in-time survey of physicians and patients with AD conducted in Japan from April to July 2019. Patients and physicians were grouped according to level of treatment satisfaction ("extremely satisfied" to "extremely dissatisfied"); with any level of dissatisfaction recorded as "less than satisfied." Data were collected on treatment patterns, clinical characteristics, and PROs including the Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), EQ-5D-3L questionnaire, and Work Productivity and Activity Impairment (WPAI) questionnaire. Results: Data were provided by 184 patients with AD and 56 physicians; 72.8% of patient–physician pairs reported a fair (kappa coefficient: 0.40) level of agreement on treatment satisfaction, 51.6% of patient–physician pairs were both satisfied, and 21.2% were both less than satisfied. Satisfied physicians prescribed a mean 1.2 fewer treatments than dissatisfied physicians (p < 0.05). Cases where both physician and patient were less than satisfied or where patients were less satisfied than their physicians reported the worst PROs, DLQI (both less than satisfied: mean 10.7 versus patient less satisfied than physician: 10.6 versus overall: 7.9), POEM (19.5 versus 17.3 versus 17.0), EQ-5D-3L (0.82 versus 0.81 versus 0.87) (all, p < 0.05). Work impairment was highest when both patient and physician were less than satisfied (p < 0.05). Physicians cited treatment efficacy and patients cited efficacy and usability as main reasons for dissatisfaction. Conclusion: Overall, 12.0% of patients were less satisfied with their AD treatment than the physician, demonstrating some of the worst PROs, suggesting unmet need that could be improved by better patient–physician communication. [ABSTRACT FROM AUTHOR]

Introduction: Upadacitinib, an oral, selective Janus kinase inhibitor, is approved in Japan for the treatment of moderate-to-severe atopic dermatitis (AD), a chronic inflammatory skin disease characterized by eczematous morphology and intense itch. Methods: Rising Up is an ongoing phase 3, randomized, multicenter study evaluating the long-term safety and efficacy of upadacitinib in Japan. Patients with moderate-to-severe AD were randomized 1:1:1 to topical corticosteroids plus upadacitinib 15 mg (UPA15), upadacitinib 30 mg (UPA30), or placebo at baseline; at week 16, placebo patients were rerandomized 1:1 to UPA15 or UPA30 (plus topical corticosteroids per investigator discretion). This 2-year interim analysis evaluated safety and efficacy through 112 weeks (data cutoff date: 11 August 2021). Adverse events (AEs), AEs of special interest (AESIs), and laboratory data were assessed. Efficacy assessments included ≥ 75% and ≥ 90% improvement from baseline in Eczema Area and Severity Index (EASI 75/90), achievement of clear or almost clear on the validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD 0/1), and ≥ 4-point improvement in the Worst Pruritus Numerical Rating Scale (WP-NRS). Results: A total of 272 patients were enrolled and 242 were ongoing at data cutoff (UPA15, n = 120; UPA30, n = 122). After 112 weeks of treatment, serious AEs, AEs leading to discontinuation, and most AESIs were generally infrequent, and rates were similar between the two upadacitinib groups. One event each of rectal cancer and cerebellar hemorrhage was reported in the UPA15 group; no thrombosis events were observed. The most common AEs included acne, nasopharyngitis, and herpes zoster. EASI 75, EASI 90, vIGA-AD 0/1, and WP-NRS response rates were maintained through week 112. Conclusion: UPA15 and UPA30 were well tolerated through 112 weeks of treatment with similar safety profiles to short-term studies and demonstrated durable long-term efficacy for the treatment of moderate-to-severe AD in adults and adolescents. Trial Registration: ClinicalTrials.gov identifier, NCT03661138. [ABSTRACT FROM AUTHOR]

Introduction: Baricitinib is an oral selective Janus kinase (JAK)1/JAK2 inhibitor approved in Japan and the European Union for the treatment of atopic dermatitis (AD). The aim of this study is to report pooled safety data for baricitinib in the Japanese subpopulation of the clinical development program in moderate-to-severe AD. Methods: This analysis included participant-level safety data from five double-blind, randomized clinical studies and one double-blind, randomized, long-term extension study, reported in three datasets for the Japanese subpopulation: (1) placebo-controlled, (2) baricitinib 2 mg and 4 mg extended ("2-mg—4-mg extended"), and (3) all baricitinib doses ("All-bari-AD"). The data cutoff was 13 December 2019. Safety outcomes included treatment-emergent adverse events, adverse events of special interest, and abnormal laboratory changes. Proportions of participants with events and incidence rates were calculated. Results: Data were collected for 341 participants from Japan who received baricitinib for 371.7 participant-years (median duration 371.0 days). In the placebo-controlled dataset, the frequencies of serious infections and herpes zoster were low and similar between treatment groups, and the incidence of treatment-emergent infections, in particular herpes simplex, was higher in the baricitinib groups compared with the placebo group. No gastrointestinal perforations, tuberculosis, positively adjudicated cardiovascular events, deep vein thrombosis, or pulmonary embolism were reported with exposure up to 2 years in the All-bari-AD dataset. There were no deaths in the Japanese subpopulation. Conclusions: This integrated safety analysis in the subpopulation of Japanese participants is consistent with the established safety profile of baricitinib in the global study population with moderate-to-severe AD. Clinicaltrials.gov identifiers: NCT02576938, NCT03334396, NCT03334422, NCT03428100, NCT03733301, and NCT03334435. [ABSTRACT FROM AUTHOR]

Introduction: Treatment satisfaction in patients with atopic dermatitis (AD) has been investigated in several studies, but the desire for alternative treatment options is unclear and has not been previously evaluated. We conducted a cross-sectional, web-based survey aimed at evaluating the desire for alternative treatment options in adults with AD from a patient registry in Japan. Methods: Main eligibility criteria were adults aged ≥ 18 years with AD who were receiving treatment with topical corticosteroids (TCS) and not systemic therapy. Questionnaires included the Patient Oriented Eczema Measure (POEM) and pruritus Numeral Rating Scale. The proportion of patients with a desire for an alternative treatment option was assessed, overall (Overall Desire) and by specific type of alternative treatment option (Specific Desire), including change in medication, hospital transfer, and complementary and alternative medicine (CAM) use. Patient background factors associated with desire were evaluated using multivariate logistic regression. Results: Of the 1500 patients included in the analysis, 91.5% (n = 1372) had an Overall Desire, with the most common Specific Desire being a change in medication (n = 1213, 80.9%), followed by CAM (n = 593, 39.5%) and hospital transfer (n = 429, 28.6%). Dissatisfaction with current treatment was significantly (p < 0.05) associated with Overall Desire and Specific Desire (p < 0.001 each). Severe disease according to POEM was significantly associated with Overall Desire and a change in medication (p < 0.001 each). Conclusions: A high proportion of Japanese patients with AD being treated with TCS had a desire for alternative treatment options. The desire was greatly affected by patients' satisfaction with their current treatment and perception of disease severity. These findings highlight the importance of assessing patients' satisfaction or perception of disease severity, and facilitating early discussions between patient and doctor on their available treatment options, including new treatment options. [ABSTRACT FROM AUTHOR]

Introduction: Baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, is indicated in the European Union and Japan for treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. In the ongoing, placebo-controlled, phase 3 trial BREEZE-AD5, once-daily oral baricitinib 2-mg monotherapy improved disease in moderate-to-severe AD patients who had an inadequate response or intolerance to topical corticosteroids. This post-hoc analysis aimed to identify responders to baricitinib 2 mg, using a proposed clinical tailoring approach based on baseline body surface area (BSA) affected and early clinical improvement, in BREEZE-AD5. Methods: Classification and regression tree method was used to evaluate baseline predictors for the proportion of patients achieving ≥ 75% improvement in Eczema Area and Severity Index (EASI75) at week 16 among baricitinib 2-mg-treated patients. Two-by-two contingency tables evaluated the association between early response, defined as ≥ 50% improvement in BSA or ≥ 3-point improvement in Itch Numeric Rating Scale from baseline at weeks 4 or 8, and response at week 16 for the proportion of patients achieving EASI75, validated Investigator Global Assessment for AD (vIGA-AD) score of 0 or 1, or ≥ 4-point improvement in Itch (Itch ≥ 4), respectively. Missing data were imputed as non-responder. Results: At week 16, EASI75 and vIGA-AD (0,1) were achieved by 37.5% and 31.7% of baricitinib 2-mg-treated patients with baseline BSA 10–50% compared with 9.5% and 4.8% with BSA > 50%. Early response in skin inflammation or itch at week 4 was associated with corresponding EASI75, vIGA-AD (0,1), and Itch ≥ 4 of 55.4%, 48.2%, and 39.3% at week 16, while early response at week 8 was associated with 66.7%, 56.1%, and 42.1% of patients achieving these endpoints. Conclusion: Baseline BSA of 10–50% and early clinical improvement after 4 or 8 weeks of baricitinib 2-mg treatment may identify patients most likely to benefit from long-term baricitinib 2-mg therapy. Clinical Trial Registration: NCT03435081. Plain Language Summary: Baricitinib is a medication that helps a dysregulated immune system readjust. This leads to improvements in the inflammatory disease atopic dermatitis (AD). Baricitinib is approved for adults with moderate-to-severe AD in over 40 countries. In the ongoing study BREEZE-AD5, baricitinib 2 mg improved moderate-to-severe AD in patients who previously did not respond to or could not tolerate topical corticosteroids. Understanding which patients are likely to benefit most from a medication can improve patient experience with treatment. It can also ensure that only patients who are likely to benefit from a medication are exposed to it. This analysis aimed to identify patients who are most likely to benefit from baricitinib 2 mg in BREEZE-AD5, using an approach based on baseline body surface area (BSA) affected and early clinical improvement. We showed that patients with moderate-to-severe AD affecting between 10% and 50% of their BSA account for the majority of patients who respond to baricitinib 2 mg after 16 weeks of treatment. Clinical assessment of skin inflammation or itch in patients after 4–8 weeks of initiation of baricitinib 2-mg treatment further improved the ability to identify patients who are most likely to benefit from long-term therapy. This proposed clinical tailoring approach of baseline BSA of 10–50% and early clinical improvement after 4 or 8 weeks of baricitinib 2-mg treatment may allow for the treatment of patients who are most likely to respond to therapy, and rapid decision on discontinuation of treatment for those who are not likely to benefit from baricitinib 2 mg. [ABSTRACT FROM AUTHOR]