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Background: Methicillin-resistant Staphylococcus aureus (MRSA) represents an important pathogen in healthcareassociated pneumonia (HCAP). The concept of HCAP, though, may not perform well as a screening test for MRSA and can lead to overuse of antibiotics. We developed a risk score to identify patients presenting to the hospital with pneumonia unlikely to have MRSA. Methods: We identified patients admitted with pneumonia (Apr 2005 - Mar 2009) at 62 hospitals in the US. We only included patients with lab evidence of bacterial infection (e.g., positive respiratory secretions, blood, or pleural cultures or urinary antigen testing). We determined variables independently associated with the presence of MRSA based on logistic regression (two-thirds of cohort) and developed a risk prediction model based on these factors. We validated the model in the remaining population. Results: The cohort included 5975 patients and MRSA was identified in 14%. The final risk score consisted of eight variables and a potential total score of 10. Points were assigned as follows: two for recent hospitalization or ICU admission; one each for age < 30 or > 79 years, prior IV antibiotic exposure, dementia, cerebrovascular disease, female with diabetes, or recent exposure to a nursing home/long term acute care facility/skilled nursing facility. This study shows how the prevalence of MRSA rose with increasing score after stratifying the scores into Low (0 to 1 points), Medium (2 to 5 points) and High (6 or more points) risk. When the score was 0 or 1, the prevalence of MRSA was < 10% while the prevalence of MRSA climbed to > 30% when the score was 6 or greater. Conclusions: MRSA represents a cause of pneumonia presenting to the hospital. This simple risk score identifies patients at low risk for MRSA and in whom anti-MRSA therapy might be withheld. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, improved itch severity, sleep, and work productivity versus placebo in patients with moderate-to-severe atopic dermatitis. Objective: The aim of this study was to investigate relationships among itch, sleep, and work productivity in the phase III JADE MONO-2 clinical trial. Methods: A repeated-measures longitudinal model was used to examine relationships between itch (using the Peak Pruritus Numerical Rating Scale [PP-NRS] or Nighttime Itch Scale [NTIS]) and sleep disturbance/loss (using the Patient-Oriented Eczema Measure sleep item and SCORing AD Sleep Loss Visual Analog Scale) and, separately, between itch and work productivity (using the Work Productivity and Activity Impairment-Atopic Dermatitis Version 2.0 questionnaire). Mediation modelling was used to investigate the effect of treatment (abrocitinib vs placebo) on work impairment via improvements in itch and sleep. Results: The relationships between itch/sleep and itch/work productivity were approximately linear. PP-NRS scores of 0, 4–6, and 10 were associated with 0 days, 3–4 days, and 7 days per week of disturbed sleep, respectively. PP-NRS or NTIS scores of 0–1, 4–5, and 10 were associated with 0–10%, 20–30%, and >50% overall work impairment, respectively. Seventy-five percent of the effect of abrocitinib on reducing work impairment was indirectly mediated by improvement in itch, followed by sleep. Conclusion: These results quantitatively demonstrate that reducing itch severity is associated with improvements in sleep and work productivity. Empirical evidence for the mechanism of action of abrocitinib showed that itch severity is improved, which reduces sleep loss/sleep disruption and, in turn, improves work productivity. Clinical Trial Registration: NCT03575871 Plain Language Summary: Atopic dermatitis (AD), also called atopic eczema, is a common skin disease that is associated with itch and reduced quality of life. Abrocitinib, a recently approved medicine for AD, was shown in clinical trials to improve itch, which is considered the most bothersome symptom to people with AD. Abrocitinib also improved sleep outcomes and work productivity in people with moderate or severe AD. It is unknown if improvement in itch can lead to improvement in sleep and work productivity. We analyzed data from the JADE MONO-2 study, which included 391 people who received treatment with abrocitinib or placebo for 12 weeks. We used mathematical modelling to study relationships between itch and sleep or work productivity. We also wanted to study if the improvements in itch and sleep with abrocitinib treatment had an impact on work productivity. We found that a relationship existed between itch, sleep disturbance, and work impairment; as itch improved, so too did sleep disturbance and work impairment. When people were treated with abrocitinib, they experienced relief from itch, which improved sleep, which in turn reduced work productivity loss. Larger and longer studies are needed to confirm these results. This analysis further informs the expectations of patients with moderate or severe AD as it relates to progression of symptom relief after treatment with abrocitinib. [ABSTRACT FROM AUTHOR]

Background: Individuals with Parkinson's disease often experience periods of off time when their motor symptoms are poorly controlled, significantly impacting their lives. Objectives: To identify the consequences of motor fluctuations on day‐to‐day activities and areas of unmet treatment priority among individuals with moderate to advanced Parkinson's disease, to assess whether existing patient‐reported outcome instruments adequately capture these consequences and priorities, and based on these evaluations, to adapt an existing or develop a new instrument. Methods: The research was conducted in 2 stages: concept exploration and content confirmation. Concept exploration included direct input from individuals with Parkinson's disease representing the intended context of use via concept elicitation interviews. Content confirmation and item refinement was achieved through 5 rounds of cognitive debriefing. Final rounds of cognitive debriefing also included usability testing of the draft instrument for electronic data capture. Results: Concept elicitation interviews were conducted among 29 individuals with Parkinson's disease (55% male; mean age 60.8 years). Concept saturation was achieved quickly with more than 90% of concepts identified by the end of the 16th interview. None of the existing outcome instruments were found to be fit for purpose in the intended context of use; therefore, a new instrument was developed. After 5 rounds, cognitive debriefing participants indicated clear and consistent interpretation of the items. Conclusions: Evidence from this study supports the content validity of the Parkinson's Disease Activities of Daily Living, Interference and Dependence Instrument as the basis of a clinical trial endpoint for capturing priority treatment benefit outcomes to individuals with moderate to advanced Parkinson's disease experiencing motor fluctuations. [ABSTRACT FROM AUTHOR]

Background: Topical treatments for atopic dermatitis (AD) used reactively often fail to achieve lasting disease control; many of these therapies are associated with safety concerns that limit long-term use. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD that has potential as a long-term maintenance therapy. Objective: The aim was to evaluate the long-term efficacy and safety of crisaborole once daily (QD) compared to vehicle QD as a maintenance therapy to reduce the incidence of flares in patients with AD who previously responded to crisaborole twice daily (BID). Methods: CrisADe CONTROL was a randomized, double-blind, vehicle-controlled, 52-week, phase III study of patients aged ≥ 3 months with mild-to-moderate AD involving ≥ 5% treatable body surface area. Eligible patients received crisaborole BID during an open-label run-in period of up to 8 weeks. Responders were randomly assigned in the double-blind maintenance period to receive either crisaborole QD or vehicle QD. Responders were defined as patients who achieved Investigator's Static Global Assessment (ISGA) success (ISGA score of 0 [clear] or 1 [almost clear] with a ≥ 2-grade improvement) and ≥ 50% improvement in Eczema Area and Severity Index total score (EASI-50) from baseline. Patients who experienced a flare (ISGA score ≥ 2) during the double-blind maintenance period switched to crisaborole BID for up to 12 weeks. During this period, patients were assessed every 4 weeks; if the flare resolved (ISGA score ≤ 1), patients resumed their assigned treatment. The primary endpoint was flare-free maintenance until onset of the first flare. Key secondary endpoints were number of flare-free days, number of flares, and maintenance of pruritus response until onset of the first flare. The incidence of treatment-emergent adverse events was also analyzed. Results: Overall, 497 patients entered the open-label run-in period with crisaborole BID, of which 270 patients were randomized into the 52-week double-blind maintenance period of the study. Of the 270 patients, 135 were randomly assigned to the crisaborole QD group and 135 were randomly assigned to the vehicle QD group. Median time of flare-free maintenance was longer for patients who received crisaborole versus vehicle (111 vs 30 days, respectively; p = 0.0034). The mean number of flare-free days was higher for patients who received crisaborole versus vehicle (234.0 vs 199.4 days, respectively; p = 0.0346). The mean number of flares was lower for patients who received crisaborole versus vehicle (0.95 vs 1.36, respectively; p = 0.0042). No clear trend was observed in maintenance of pruritus response between crisaborole- and vehicle-treated patients. Crisaborole was well tolerated, with no new or unexpected safety findings when used as maintenance treatment. Conclusions: Crisaborole QD was effective and well tolerated for long-term maintenance treatment and flare reduction in adult and pediatric patients with mild-to-moderate AD. Trial Registration: ClinicalTrials.gov, NCT04040192, 31 July 2019. Plain Language Summary: Atopic dermatitis (AD) is an immuno-inflammatory skin disease that can last a long time. It causes skin lesions and intense itching. Topical AD treatments used reactively often fail to control the disease over a long period of time. Many are associated with safety concerns that limit long-term use. Crisaborole ointment is a nonsteroidal treatment for the skin and is used to treat mild-to-moderate AD. Previous studies showed that using crisaborole twice daily was effective and had few side effects in patients with mild-to-moderate AD. This study evaluated how effective and safe long-term treatment with once-daily crisaborole was compared with an ointment with no drug (vehicle). The study included patients aged ≥ 3 months with mild-to-moderate AD whose AD improved after previous treatment with twice-daily crisaborole. This study was designed to investigate how much crisaborole reduced the incidence of AD flares over 52 weeks in these patients. The study included 270 patients whose AD had improved after treatment with twice-daily crisaborole. Of these patients, 135 were randomly assigned to receive crisaborole once a day and 135 to receive vehicle once a day. Patients who received crisaborole had a significantly longer time before experiencing AD flares than those who received vehicle. Crisaborole was well tolerated, and no new or unexpected side effects were found when used as a once-daily maintenance treatment for 52 weeks. These results indicate that once-daily treatment with crisaborole could be a potential long-term maintenance treatment option in children and adults with mild-to-moderate AD. [ABSTRACT FROM AUTHOR]

Introduction: Using data from three clinical trials, the effect of crisaborole treatment on sleep outcomes for pediatric patients with atopic dermatitis (AD) and their families was examined. Methods: This analysis comprised patients aged 2 to < 16 years from the double-blind phase 3 CrisADe CORE 1 (NCT02118766) and CORE 2 (NCT02118792) studies, families of patients aged 2 to < 18 years from CORE 1 and CORE 2, and patients aged 3 months to < 2 years from the open-label phase 4 CrisADe CARE 1 study (NCT03356977), all with mild-to-moderate AD who received crisaborole ointment 2% twice daily for 28 days. Sleep outcomes were assessed via the Children's Dermatology Life Quality Index and Dermatitis Family Impact questionnaires in CORE 1 and CORE 2 and the Patient-Oriented Eczema Measure questionnaire in CARE 1. Results: In CORE 1 and CORE 2, a significantly lower proportion of crisaborole-treated patients than vehicle-treated patients reported sleep disruption at day 29 (48.5% versus 57.7%, p = 0.001). The proportion of families whose sleep was affected by their child's AD in the preceding week was also significantly lower in the crisaborole group (35.8% versus 43.1%, p = 0.02) at day 29. At day 29 in CARE 1, the proportion of crisaborole-treated patients who experienced ≥ 1 night of disturbed sleep in the previous week decreased by 32.1% from baseline. Conclusion: These results suggest that crisaborole improves sleep outcomes in pediatric patients with mild-to-moderate AD and their families. Plain Language Summary: Atopic dermatitis (AD), also known as eczema, is a chronic skin disease that causes red or flaky skin patches that can become infected and itch. Children with AD often experience sleep disturbance, including difficulty falling asleep, restless sleep, waking up more frequently, and daytime drowsiness. Problems with sleep quality negatively impact children with AD, as well as their caregivers. Crisaborole ointment is applied to the skin and has been shown to improve the symptoms of AD in children and adults. This study examined how treatment with crisaborole affected sleep quality for children and their caregivers in three clinical trials. Children in these studies took crisaborole for 28 days. Researchers found that crisaborole treatment improved sleep in children with mild-to-moderate AD and their caregivers. This was determined using four measures. First, a smaller proportion of children who were treated with crisaborole experienced sleep disruption compared with those to whom a vehicle was applied (an ointment with no drug). Second, a smaller proportion of caregivers of children with AD who were treated with crisaborole reported effects on their sleep, compared with children to whom a vehicle was applied. Third, a smaller proportion of children with AD who were treated with crisaborole, as well as their caregivers, had ≥ 1 night per week of disturbed sleep after treatment compared with before treatment. Fourth, the caregivers of children treated with crisaborole reported significantly less exhaustion and tiredness because of the child's AD. These results suggest that treatment with crisaborole improves sleep outcomes in children with mild-to-moderate AD and their caregivers. [ABSTRACT FROM AUTHOR]

Background: Methicillin-resistant Staphylococcus aureus (MRSA) represents an important pathogen in healthcare-associated pneumonia (HCAP). The concept of HCAP, though, may not perform well as a screening test for MRSA and can lead to overuse of antibiotics. We developed a risk score to identify patients presenting to the hospital with pneumonia unlikely to have MRSA.Methods: We identified patients admitted with pneumonia (Apr 2005-Mar 2009) at 62 hospitals in the US. We only included patients with lab evidence of bacterial infection (e.g., positive respiratory secretions, blood, or pleural cultures or urinary antigen testing). We determined variables independently associated with the presence of MRSA based on logistic regression (two-thirds of cohort) and developed a risk prediction model based on these factors. We validated the model in the remaining population.Results: The cohort included 5975 patients and MRSA was identified in 14%. The final risk score consisted of eight variables and a potential total score of 10. Points were assigned as follows: two for recent hospitalization or ICU admission; one each for age < 30 or > 79 years, prior IV antibiotic exposure, dementia, cerebrovascular disease, female with diabetes, or recent exposure to a nursing home/long term acute care facility/skilled nursing facility. This study shows how the prevalence of MRSA rose with increasing score after stratifying the scores into Low (0 to 1 points), Medium (2 to 5 points) and High (6 or more points) risk. When the score was 0 or 1, the prevalence of MRSA was < 10% while the prevalence of MRSA climbed to > 30% when the score was 6 or greater.Conclusions: MRSA represents a cause of pneumonia presenting to the hospital. This simple risk score identifies patients at low risk for MRSA and in whom anti-MRSA therapy might be withheld. [ABSTRACT FROM AUTHOR]

Background Skin pain is a common and burdensome symptom of atopic dermatitis (AD), and its severity increases with disease progression. The Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) is a validated 11-item patient-reported instrument developed in accordance with regulatory agency guidance for assessment of the daily symptoms of patients with AD, including skin pain. Objective To establish content validity and evaluate the psychometric properties of the skin pain numerical rating scale (NRS) item of the PSAAD. Methods: The skin pain NRS is a single-item measure from the PSAAD and is used to assess skin pain severity over the past 24 hours with the question "How painful was your skin over the past 24 hours?" on a 10-point scale from 0 (not painful) to 10 (extremely painful). A qualitative validation analysis consisting of concept elicitation (CE) interviews; electronic completion of the PSAAD measure, including the skin pain NRS; and cognitive debriefing (CD) interviews was conducted for adults and adolescents with mild-to-severe AD. Evaluation of psychometric properties of the skin pain NRS--including test-retest reliability, estimation of meaningful within-patient change (MWPC), known-group validity, ability to detect change, construct validity, quality of completion, and ceiling and floor effects--was conducted based on a post hoc qualitative and quantitative analysis of pooled data, with skin pain NRS as part of the PSAAD in the abrocitinib monotherapy phase 3 trials JADE MONO-1 (NCT03349060) and JADE MONO-2 (NCT03575871). Data from patients (≥12 years of age) with moderate-to-severe AD were pooled across all treatment arms. Results: Among 30 CE interviews (adolescents [12-17 years], n=15; adults [≥18 years], n=15) conducted over 2 rounds of testing, 20 of 30 (67%) patients reported skin pain. During CD interviews (n=30), 100% of patients interpreted the skin pain NRS item as intended, and 73% reported it as relevant. The psychometric validation analysis included 736 patients (JADE MONO-1, N=347; JADE MONO-2, N=389). The test-retest reliability of the skin pain NRS was evidenced by large intraclass correlation coefficients (ICC; 0.76 and 0.72 in JADE MONO-1 and MONO-2, respectively) for a single daily skin pain score, which increased to 0.93 and 0.91 for a measurement averaging at least 4 scores per week. Convergent validity was demonstrated by correlations between skin pain and other clinician- and patient-reported AD measures (median correlation >0.4 starting at week 4). The skin pain NRS distinguished between "clear" and "severe" disease severity groups, assessed using the Patient Global Assessment (PtGA) and Investigator's Global Assessment (IGA) as continuous and categorical anchors (P<0.0001); differences were also significant among other disease severity groups using the PtGA and IGA as continuous anchors (P<0.0001). Based on the PtGA and IGA anchor analysis, the estimated MWPC was 1.9 and ranged from 2.7 to 3.9 points using the empirical cumulative distribution function analysis. Ability to detect change was demonstrated by linear relationships between disease severity measures and skin pain scores (correlation of ≥0.5 between the skin pain NRS and the PtGA). More than 90% of patients provided at least 4 daily skin pain scores each week. No floor or ceiling effects were observed. Conclusions: The qualitative and quantitative data from initial PSAAD development and psychometric evaluation of the skin pain NRS from the PSAAD support its content validity, reliability, construct validity, and ability to detect change. These findings corroborate the 4-point improvement in skin pain as the adequate and meaningful cut-off to define a skin pain responder in JADE MONO-1 and MONO-2. [ABSTRACT FROM AUTHOR]

The expanding number of potential treatment options for atopic dermatitis (AD) highlights the need to better understand the treatment preferences of individuals with AD. This study identified attributes that most greatly influenced treatment preferences of adults/adolescents/caregivers of children with mild/moderate/severe AD. Adults (≥18 years), adolescents (12–17 years), and caregivers of children (2–11 years) with mild, moderate, or severe AD in the United States (US) and United Kingdom (UK) participated in semistructured interviews. Thematic analysis was used to identify and generate themes across the interview results describing the treatment attributes of greatest importance to participants. Qualitative interviews were conducted with 35 adults, 35 caregivers, and 33 adolescent participants across both countries (n = 103; US = 51; UK = 52) and all severity groups (mild = 43; moderate = 47; severe = 13). The most important treatment attributes included efficacy (96.1%; speed and duration of symptom relief), mode of administration (66.0%; route of administration, frequency, and convenience), and side effects (55.3%, short-term, long-term, and general). Efficacy, mode of administration, and side effects were the most important attributes that influenced AD treatment preferences for patients and caregivers across different countries, ages, and disease severity. These results may assist patients/caregivers/clinicians in shared decision-making discussions to improve treatment adherence and outcomes. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Introduction: The Investigator's Static Global Assessment (ISGA) is a 5-point rating scale that is recommended by the US Food and Drug Administration for assessing the severity of atopic dermatitis (AD), and ISGA success is a widely used endpoint in AD clinical studies. In this study, we seek to interpret the relationship of ISGA with treatment, pruritus, and quality of life (QoL) by conducting post hoc analyses of pooled data from two phase 3 crisaborole studies. Methods: Patients aged ≥ 2 years with baseline ISGA of 2 (mild) or 3 (moderate) were randomly assigned 2:1 to receive crisaborole or vehicle for 28 days. Disease severity, pruritus severity, and QoL were assessed with the ISGA, Severity of Pruritus Scale (SPS), and Dermatology Life Quality Index (DLQI; patients aged ≥ 16 years), or Children's Dermatology Life Quality Index (CDLQI; patients aged 2–15 years), respectively. The effect of treatment on ISGA and the relationship between ISGA and QoL were analyzed using a longitudinal repeated-measures model. The interrelationship between treatment, disease severity, pruritus, and QoL was analyzed with a mediation model. Results: Overall, 1522 patients (crisaborole, n = 1016; vehicle, n = 506) were included. Estimated longitudinal profiles indicated changes in ISGA by day 8 were large for crisaborole (effect size [ES]: − 0.68) and small for vehicle (ES: − 0.34). There was a direct relationship between ISGA and DLQI and CDLQI severity bands in the longitudinal repeated-measures model. For both QoL mediation models, treatment effects on QoL were mediated indirectly by reduction in pruritus (DLQI, 42.4%; CDLQI, 58.1%) and disease severity (DLQI, 12.2%; CDLQI, 33.1%). Conclusions: These post hoc analyses suggest that ISGA success is a clinically meaningful endpoint associated with reduction in the severity of pruritus and improvement in QoL. [ABSTRACT FROM AUTHOR]

Background/Objectives: Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild‐to‐moderate atopic dermatitis (AD). This pooled post hoc analysis of two phase 3 trials (NCT02118766, NCT02118792) assessed improvement and time to improvement in Investigator's Static Global Assessment (ISGA) and Severity of Pruritus Scale (SPS) outcomes in pediatric patients with mild‐to‐moderate AD. Methods: Patients aged ≥2 years were randomly assigned 2:1 to receive twice‐daily crisaborole or vehicle for 28 days. Patients aged 2‐17 years were pooled for this analysis. Proportions of patients and time to achieving ISGA success (clear [0] or almost clear [1] with ≥2‐grade improvement from baseline), ISGA clear/almost clear, ≥1‐grade improvement in ISGA, SPS success (SPS score ≤1 with ≥1‐grade improvement), or ≥1‐grade improvement in SPS score were analyzed and stratified by baseline ISGA. Results: At first postbaseline assessment (day 8), significantly higher proportions of crisaborole‐ than vehicle‐treated patients achieved ISGA success, ISGA clear/almost clear, ≥1‐grade ISGA improvement, SPS success, or ≥1‐grade improvement in SPS regardless of baseline ISGA. Differences were significantly greater over time for all outcomes for patients with moderate baseline ISGA and numerically greater for those with mild baseline ISGA. Median times to ISGA and SPS outcomes were shorter for crisaborole versus vehicle. Conclusion: Improvement in ISGA and SPS outcomes were observed with crisaborole in pediatric patients with mild‐to‐moderate baseline AD. [ABSTRACT FROM AUTHOR]

Skin pain is a common and bothersome symptom of atopic dermatitis (AD) that is associated with a substantial burden. To assess the efficacy of abrocitinib vs. dupilumab on skin pain in patients with moderate-to-severe AD. Data from patients aged ≥18 years who received oral abrocitinib 200 mg once daily (QD) or subcutaneous dupilumab 300 mg once every 2 weeks in combination with topical therapy in the phase 3 trials JADE COMPARE (NCT03720470) and JADE DARE (NCT04345367) were analysed. Data from patients who received abrocitinib 100 mg QD or placebo in the JADE COMPARE trial were also included in this analysis. Patients rated their skin pain using the Skin Pain Numerical Rating Scale (NRS) item of the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) instrument ['How painful was your skin over the past 24 h?' on a scale from 0 (not painful) to 10 (extremely painful) ] in JADE COMPARE or the Skin Pain Numerical Rating Scale [SP-NRS, which queried patients for the severity of their 'worst skin pain' in the past 24 h on a scale from 0 (no skin pain) to 10 (worst skin pain imaginable)] in JADE DARE. Least squares mean (LSM) changes from baseline and proportions of patients who achieved a ≥4-point improvement from baseline in PSAAD skin pain score or SP-NRS were assessed through Week 16 (JADE COMPARE) or Week 26 (JADE DARE). The JADE COMPARE analysis (Skin Pain NRS item of the PSAAD) was performed post hoc, whereas the JADE DARE analysis (SP-NRS) was prespecified. At Week 2 of JADE COMPARE, LSM change from baseline in PSAAD skin pain score was greater with abrocitinib 200 mg [−2.8 (95% CI, −3.1, −2.5)] than with abrocitinib 100 mg [−2.1 (−2.3, −1.8)], dupilumab [−2.0 (−2.3, −1.8)], or placebo [−1.3 (−1.6, −0,9)]; improvements were sustained through Week 16 of treatment with abrocitinib 200 mg [−4.1 (−4.4, −3.8)], abrocitinib 100 mg [−3.3 (−3.6, −3.0)] and dupilumab [−4.0 (−4.2, −3.7)] compared with placebo [−1.8 (−2.2, −1.4)]. In JADE DARE, LSM change from baseline in SP-NRS was significantly greater with abrocitinib 200 mg vs. dupilumab at Week 2 [−3.7 (−3.9, −3.4) vs. −2.6 (−2.8, −2.3); P < 0.0001] and week 12 [−4.5 (−4.7, −4.2) vs. −4.0 (−4.3, −3.8); P = 0.0116]; no significant differences were observed between the treatment arms at Week 16 [−4.4 (−4.7, −4.2) vs. −4.2 (−4.4, −4.0); P = 0.16], Week 20 [−4.8 (−5.0, −4.5) vs. −4.5 (−4.7 vs. −4.2); P = 0.06] or Week 26 [−4.5 (−4.8, −4.3)] vs. −4.3 (−4.6, −4.1); P = 0.27]. The proportions of patients who achieved a ≥4-point improvement in PSAAD skin pain score at week 2 of JADE COMPARE were greater with abrocitinib 200 mg (43%) than with abrocitinib 100 mg (23%), dupilumab (24%) or placebo (14%). At Week 16, these proportions increased to 76% (abrocitinib 200 mg), 57% (abrocitinib 100 mg) and 70% (dupilumab) compared with placebo (29%). In JADE DARE, the proportions of patients who achieved a ≥4-point improvement in SP-NRS were significantly greater with abrocitinib 200 mg vs. dupilumab at Week 2 (58% vs. 36%; P < 0.0001) and Week 12 (71% vs. 61%; P = 0.0098) but not at subsequent timepoints. Similar to previous findings on the effect of abrocitinib on itch, these results suggest that abrocitinib 200 mg provides greater early skin pain relief in patients with moderate-to-severe AD compared with dupilumab, but the difference between the treatments diminishes with time. At earlier time points, skin pain improvement with abrocitinib 100 mg was similar to that with dupilumab. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with itch, eczematous lesions and impaired quality of life (QoL). Although the frequency of skin pain in AD is often underestimated, it is associated with a substantial health burden, similar to itch and is known to contribute to sleep disruption and mood disturbance. Abrocitinib is an oral, once-daily, selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe AD. In phase 3 clinical trials JADE MONO-1 (NCT03349060) and JADE MONO-2 (NCT03575871), abrocitinib demonstrated rapid relief from itch and skin pain, as well as meaningful improvements in QoL compared with placebo. The interrelationships between abrocitinib treatment and improvements in itch, skin pain and QoL have not yet been investigated. This mediation analysis aimed to characterize the effect of abrocitinib treatment via itch and skin pain on dermatology-specific QoL in patients with AD. Data from JADE MONO-1 and JADE MONO-2 were pooled in this analysis. Adult patients with moderate-to-severe AD received abrocitinib (200 or 100 mg) as monotherapy or placebo for 12 weeks. Three separate models were evaluated whereby QoL was assessed using the Dermatology Life Quality Index (DLQI) score, and itch and skin pain were assessed via the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) items #1 (How itchy was your skin over the past 24 h?) and #2 (How painful was your skin over the past 24 h?), respectively. The cross-sectional mediation model (CSMM) was run separately at weeks 2, 4, 8 and 12 using all available data at each timepoint. The longitudinal mediation model (LMM), which does not assume independence among measurements of itch, skin pain and DLQI at each timepoint, estimated relationships using all available data from all weeks simultaneously. Based on the results of the CSMM and LMM, a pseudosteady-state model, in which the relationship among variables was assumed to be the same across timepoints, was applied. Effects with P<0.05 were considered statistically significant. In the CSMM, the indirect effect of abrocitinib on DLQI mediated via itch was considered approximately stable (24–30%) for the first 8 weeks before increasing at week 12 (42%), while the indirect effect mediated via skin pain was considered approximately stable from week 2 to week 12 (33–41%). In the LMM, the indirect effect of abrocitinib treatment on DLQI mediated via both itch and skin pain was considered approximately stable from week 2 to week 12 (17–26% and 42–48%, respectively). The cross-sectional and longitudinal models were generally consistent and indicated a pseudo-steady-state period between weeks 2 and 12. Using the pseudo-steady-state model, the direct effect of abrocitinib on DLQI was estimated to be 34.8% (P<0.0001), and the indirect effects mediated via itch and skin pain were estimated to be 19.5% and 45.8%, respectively (P≤0.0001 for both). Improvements in dermatology-specific QoL with abrocitinib are mostly mediated indirectly via a reduction in skin pain and less so by relief of itch. These findings warrant further research to examine to what extent patients consider itch and skin pain as separate concepts in terms of their impact on dermatology-specific QoL. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense itch, skin pain and impaired quality of life. Skin pain is a common and bothersome symptom of AD and increases in prevalence and intensity with worsening disease severity. Abrocitinib is an oral, once-daily, selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe AD. Abrocitinib treatment resulted in improvements in skin clearance as well as rapid itch reduction in patients with moderate-to-severe AD across multiple phase 3 studies. Work productivity loss and activity impairment were assessed in the phase 3 JADE MONO-2 (NCT03575871) trial, with greater improvements being associated with abrocitinib treatment compared with placebo. The mechanism(s) through which abrocitinib reduces work productivity loss and activity impairment are unclear. To describe the interrelationships among abrocitinib treatment, itch, skin pain, and work productivity and activity impairment using a mediation modelling analysis in patients with AD. Data from adult patients treated with abrocitinib monotherapy (200 or 100 mg) or placebo in JADE MONO-2 were included in this analysis. As separate outcomes, work productivity loss and activity impairment (outcome variables) were measured by the Work Productivity and Activity Impairment Questionnaire: Atopic Dermatitis version 2.0 (WPAI-AD 2.0). Itch and skin pain (mediator variables) were evaluated using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) item #1 (How itchy was your skin over the past 24 h?) and item #2 (How painful was your skin over the past 24 h?), respectively. Mediation modelling was conducted independently for work productivity loss and activity impairment. All available data at week 12 were used in the modelling. Effects with P<0.05 were considered statistically significant. The direct effects of abrocitinib were estimated to be 7.3% (P=0.779) and 17.5% (P=0.258) on work productivity loss and activity impairment, respectively. The indirect effects of abrocitinib treatment on work productivity loss and, separately, on activity impairment mediated via itch were estimated to be 50.6% (P=0.017) and 20.9% (P=0.062), respectively, and via skin, pain were estimated to be 42.1% and 61.5%, respectively, (P<0.05 for both). The indirect effect of abrocitinib treatment on work productivity loss is mediated approximately equally through the reduction in itch severity and skin pain. The effect of abrocitinib treatment on activity impairment is mostly mediated indirectly through the reduction of skin pain, along with a smaller indirect contribution from the reduction in itch. These findings support further research into the extent that patients consider itch and skin pain as separate concepts in terms of their impact on work productivity. [ABSTRACT FROM AUTHOR]

Treatments for atopic dermatitis (AD) often fail to achieve lasting disease control despite patient adherence, with safety concerns limiting the long-term use of many therapies. Crisaborole ointment, 2%, is a nonsteroi - dal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. Crisaborole has the potential as a long-term maintenance therapy. To assess the long-term efficacy and safety of crisaborole once daily as a maintenance treatment to reduce the incidence of flares in patients who had achieved response with treatment with crisaborole twice daily. CrisADe CONTROL (NCT04040192) was a randomized, double-blind, vehicle-controlled, 52-week, phase 3 study of patients aged ≥3 months with mild-to-moderate AD involving ≥5% treatable body surface area. In an open-label run-in period, patients received crisaborole twice daily for up to 8 weeks. Patients who achieved success per Investigator’s Static Global Assessment (ISGA; ISGA score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline) and ≥50% reduction from baseline on the Eczema Area and Severity Index during the run-in were randomly assigned to receive blinded crisaborole or vehicle once daily during the 52-week maintenance period. Patients who experienced a flare (ISGA score ≥2) during the maintenance period switched to crisaborole twice daily for up to 12 weeks (assessed every 4 weeks); if the flare resolved (ISGA score ≤1), patients resumed their blinded once-daily treatment. Endpoints included flare-free maintenance until the onset of the first flare (primary), the number of days without flare and the number of flares. The incidence of treatment-emergent adverse events was also evaluated. Of 270 randomly assigned patients, 135 were assigned to crisaborole and 135 to a vehicle once daily. The median time of flare-free maintenance was longer for patients treated with crisaborole vs. vehicle (111 vs. 30 days, respectively; P=0.0034). The mean number of flare-free days was higher for patients treated with crisaborole vs. vehicle (234.0 vs. 199.4, respectively; P=0.0346). The mean number of flares was lower for patients treated with crisaborole vs. vehicle (0.95 vs. 1.36, respectively; P=0.0042). Crisaborole was well tolerated, with no unexpected safety findings or new safety signals when used as a maintenance treatment for 52 weeks. Once-daily treatment with crisaborole was effective and well tolerated for long-term maintenance treatment and flare reduction in adult and paediatric patients with mild-to-moderate AD. [ABSTRACT FROM AUTHOR]

Purpose: Results from studies comparing health care resource use (HCRU), costs of treatment, and costeffectiveness of linezolid compared with vancomycin therapy in the treatment of hospitalized patients with methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia are limited in the published literature. We therefore conducted an analysis to compare the HCRU, costs of treatment, and cost-effectiveness of linezolid compared with vancomycin in the treatment of hospitalized patients with MRSA nosocomial pneumonia using data from a Phase IV clinical trial. The economic effect of moderate to severe adverse events (MSAEs) and the development of renal failure were also evaluated. Methods: We performed a post hoc analysis of data from a Phase IV, double-blind, randomized, comparatorcontrolled, multicenter trial that compared linezolid and vancomycin treatment in patients with MRSA nosocomial pneumonia. HCRU and costs were compared based on treatment, development of MSAEs, and development of renal failure using data from the modified intent-totreat population. Predictors of costs were evaluated using generalized linear models. A piggyback cost-effectiveness analysis was conducted to assess the incremental costeffectiveness ratio of linezolid versus vancomycin, given the significantly higher clinical success of linezolid compared with vancomycin found in the trial. Findings: Overall, HCRU and costs were similar between the linezolid and vancomycin treatment groups; drug costs were significantly higher and dialysis costs significantly lower for linezolid- compared with vancomycin-treated patients. Total treatment costs were approximately $8000 higher (P = .046) for patients who developed renal failure compared with those who did not. Renal failure occurred more commonly in patients randomized to receive vancomycin (15%) compared with linezolid (4%; P < .001). Region, ventilator-associated pneumonia, clinical failure, and development of renal failure were associated with significantly higher total costs. The point estimate incremental cost-effectiveness ratio for linezolid compared with vancomycin was $16,516 per treatment success, with linezolid dominant in 24% and dominated in o2% of bootstrapped samples. Implications: This phase 4 clinical trial conducted in patients with MRSA-confirmed nosocomial pneumonia reveals that linezolid- compared with vancomycintreated patients had similar HCRU and total overall costs. Fewer patients developed renal failure during the study while taking linezolid compared with vancomycin, and patients with a documented MSAE or renal failure had increased HCRU and costs. In summary, linezolid may be a cost-effective treatment strategy in MRSA-confirmed nosocomial pneumonia. [ABSTRACT FROM AUTHOR]

A correction to the article "Impact of Oral Abrocitinib Monotherapy on Patient-Reported Symptoms and Quality of Life in Adolescents and Adult with Moderate-to-Severe Atopic Dermatitis: A Pooled Analysis of Patient-Reported Outcomes" in an issue is presented.

Summary: Objective: To compare outcomes of treating complicated skin and skin structure infections (cSSSI) caused by methicillin-resistant Staphylococcus aureus (MRSA) with linezolid versus vancomycin in diabetic and non-diabetic patients. Methods: We pooled data from three prospective clinical trials in which 1056 patients were randomized to receive either linezolid (intravenous (IV) or oral) or vancomycin (IV) every 12h, for 7–28 days. Results: Diabetic (n =349) and non-diabetic patients (n =707) had comparable demographics and co-morbidities. Clinical success rates were lower in diabetic than in non-diabetic patients (72.3% and 85.8%, respectively). Overall, non-diabetic patients had a shorter adjusted mean length of stay (LOS) compared with diabetic patients (8.2 and 10.7 days, respectively; p <0.0001). Among diabetic patients, rates were comparable with linezolid and vancomycin treatment for clinical success (74% and 71%, respectively) and microbiological success (60% and 54%, respectively). Among non-diabetic patients, clinical and microbiological success rates were higher in linezolid- than in vancomycin-treated patients (90% and 81%, respectively, and 78% and 65%, respectively). Rates of drug-related adverse events were comparable in diabetic and non-diabetic patients and with linezolid and vancomycin treatment. Adjusted mean LOS was shorter with linezolid than with vancomycin treatment in diabetic patients (9.5 and 11.7 days, respectively; p =0.03) and non-diabetic patients (7.6 and 8.9 days, respectively; p =0.02). Conclusions: Clinical success rates were lower in diabetic than non-diabetic patients with cSSSI caused by MRSA. Comparing linezolid and vancomycin, clinical and microbiological success rates were comparable in diabetic patients, but were better for linezolid than for vancomycin in non-diabetic patients. [ABSTRACT FROM AUTHOR]