Faculty Bibliography

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with intense pruritus. It has a profound impact on health-related quality of life (HRQoL). In two identical phase III studies [JADE MONO-1 (NCT03349060) and JADE MONO-2 (NCT03575871)] abrocitinib, a Janus kinase 1 selective inhibitor, was shown rapidly to reduce pruritus in patients with moderate-to-severe AD vs. placebo. This post-hoc analysis of the JADE MONO-1 and MONO-2 trials aimed to quantify the relationship between pruritus severity and HRQoL in patients with moderate-to-severe AD. Adults (aged >= 18years) with moderate-to-severe AD [affected body surface area >= 10%; Eczema Area and Severity Index (EASI) score >= 16; Investigator's Global Assessment (IGA) score >= 3; Peak Pruritus Numerical Rating Scale (PP-NRS; the PP-NRS is used with permission of Regeneron Pharmaceuticals, Inc., and Sanofi) score >= 4] were randomly assigned 2: 2: 1 to receive once-daily abrocitinib 200mg or 100mg or placebo for 12weeks. Pruritus severity was assessed using the PP-NRS daily during the first 2weeks of the study, then as single measurements at weeks 4, 8 and 12. Disease-specific HRQoL was assessed using the Dermatology Life Quality Index (DLQI) at baseline and at weeks 2, 4, 8 and 12, and general HRQoL was assessed using the Short Form-36 Heath Survey Version 2 (SF-36v2; Medical Outcomes Trust) at baseline and at week 12. Data from the abrocitinib and placebo arms were pooled. A repeated-measures longitudinal model was used to estimate the relationship between HRQoL (outcome) and pruritus (using PP-NRS as the predictor). The outcome was either one of the eight SF-36 domains or two summary scores (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, Mental Health, Physical Component Summary, or Mental Component Summary) or DLQI total score. SF-36 norm-based standardized T scores (with a mean of 50 and an SD of 10 reflecting normative scores for the US general population) were used. To assess the validity of the linear approximation of the relationship between predictor and outcome, the model was also implemented with the PP-NRS as a categorical variable, which does not impose any functional relationship between predictor and outcome. Data from 654 and 642 patients were available for the DLQI and SF-36 analyses, respectively. Approximately linear relationships were found between PP-NRS scores and either measure of HRQoL indicating a direct association between severity of itch and dermatology HRQoL (via DLQI) or general HRQoL (via SF-36v2). A 3-point improvement in PP-NRS score corresponded, on average, to a clinically meaningful 4.7-point change in DLQI score; PP-NRS scores of 0, 1-2, 3-5 and >= 6 were associated with no, small, moderate and very large effects of their disease on HRQoL (as assessed by DLQI), respectively (Figure1). A 3-point improvement in PP-NRS corresponded, on average, to clinically important changes in the Role Physical (3.9 points), Bodily Pain (5.6 points) and Physical Component Summary (3.9 points) domains of SF-36, whereas a 4-point improvement in PP-NRS score was associated with clinically important change in Social Functioning (5.4 points); PP-NRS scores >= 1 were associated with SF-36 scores higher than US general population norms adjusted for age and sex for all SF-36 domains except General Health, whereas PP-NRS scores > 5 were associated with lower than US general population norms adjusted for age and sex for all domains. In this post-hoc analysis, pooled data from JADE MONO-1 and MONO-2 showed that severity of itch was strongly associated with HRQoL in patients with moderate-to-severe AD. Moreover, although the current threshold for clinically meaningful change in studies to investigate abrocitinib is a 4-point improvement in PP-NRS score, these results suggest that a 3-point change may be sufficient for clinically meaningful improvement in HRQoL as measured by the DLQI and the Role Physical and Bodily Pain domains and Physical Component Summary score of the SF-36

Atopic dermatitis (AD) disproportionately affects Asian and Black/African American individuals, compared to white individuals in the US population. In addition, clinical manifestations of AD can differ by skin type. Therefore, it is important to understand the effectiveness of AD treatments in individuals with different skin types. The objective of this study was to compare the efficacy of abrocitinib, an oral, once-daily Janus kinase 1 selective inhibitor, among study participants of different skin types. This post-hoc analysis included data pooled from two phase III studies [NCT03349060 (JADE MONO-1) and NCT03575871 (JADE MONO-2)] and one phase IIb study (NCT02780167). In all three studies, participants aged >= 12years (phase III studies) or aged >= 18years (phase II study) with moderate-to-severe AD were randomly assigned to receive oral abrocitinib 200mg, abrocitinib 100mg or placebo once daily for 12weeks. Endpoints were the proportion of patients who achieved Investigator's Global Assessment (IGA) response [clear (0) or almost clear (1) with >= 2 grade improvement], >= 75% improvement in Eczema Area and Severity Index (EASI-75) score, 4-point improvement in Peak Pruritus Numeric Rating Scale (PP-NRS4; the PP-NRS is used with permission of Regeneron Pharmaceuticals, Inc., and Sanofi) and >= 75% improvement in SCORing Atopic Dermatitis (SCORAD-75) score at week 12. Patients self-reported their racial subgroup. This analysis included data from white, Asian and black participants. The statistical difference between treatment groups and placebo were assessed using the Cochran-Mantel-Haenszel test. In this study, abrocitinib 200mg or 100mg or placebo was administered to white (232, 254 and 142, respectively), black (30, 31 and 22) and Asian (85, 80 and 39) participants. At week 12, IGA response was significantly greater in participants receiving abrocitinib 200mg or 100mg vs. placebo in white (43.1% and 24.4% vs. 8.8%, both P<0.001), black (27.6% and 35.5% vs. 0%, both P<0.01) and Asian participants (37.6% and 30.4% vs. 10.3%, both P<0.05). Similar results were observed in white and Asian participants for EASI-75 [white: 64.3% and 39.2% vs. 12.5%; Asian: 61.2% and 48.1% vs. 12.8% (all P<0.001)], PP-NRS4 [white: 61.2% and 38.2% vs. 16.8%; Asian: 49.3% and 47.8% vs. 8.6% (all P<0.001)] and SCORAD-75 [62.5% and 37.4% vs. 20.8% (both P<0.01); 60.5% and 43.1% vs. 22.2% (both P<0.05)]. EASI-75 response was significantly different from that with placebo (13.6%) in black participants receiving 100mg (48.4%) but not 200mg abrocitinib (37.9%). PP-NRS4 and SCORAD-75 responses were numerically greater but not significantly different in black participants receiving abrocitinib 200mg or 100mg vs. placebo (PP-NRS4: 39.3% and 53.8% vs. 28.6%; SCORAD-75: 56.5% and 47.8% vs. 33.3%). For each of the different skin types, participants taking abrocitinib had a significant improvement with abrocitinib vs. placebo for patient-reported outcomes (PROs), including Dermatology Life Quality Index and Patient-Oriented Eczema Measure scores. Rates of adverse events (AEs) were numerically higher in with 200-mg and 100-mg treatment vs. placebo arm and were greater in white (75.4% and 69.7% vs. 60.6%) and black participants (66.7% and 74.2% vs. 45.5%) than in Asian participants (64.7% and 58.8% vs. 41.0%); study discontinuation because of AEs also occurred more with white (6.9%, 8.7% and 13.4%, respectively) and black (10.0%, 6.5% and 18.2%, respectively) participants than with Asian participants (3.5%, 3.8% and 5.1%, respectively); study discontinuation occurred more frequently in the placebo arm and across all racial subgroups, presumably because of uncontrolled AD. In this post-hoc analysis, monotherapy with abrocitinib 200mg or 100mg was more effective than placebo in improving moderate-to-severe AD in white, black and Asian participants, as measured by IGA response and PROs; similar results were observed for >= 75% improvement in Eczema Area and Severity Index, PP-NRS4 and >= 75% decrease in SCORing AD (SCORAD-75) but were only statistically significant in white and Asian participants. The rate of AEs was higher in white and black participants than in Asian participants, but discontinuation rates for treatment were low across all racial subgroups. Lower clinical efficacy and absence of dose response in participants with black skin might be a result of the relatively small population with black skin included in the analysis. Greater representation of participants with black skin in future studies is warranted

Occupation contact dermatitis (CD) is a common inflammatory skin condition impacting every professional industry in the United States. It is associated with significant personal and professional distress, loss of revenue, and decreased productivity. Occupational CD is further subdivided into irritant CD and allergic CD. Frequently, workers may suffer from a combination of both types. Numerous workplace exposures are implicated, but there are several themes across professions, such as CD related to frequent handwashing and wet work. A detailed occupational history, physical examination, and patch testing can help to make the diagnosis. Treatment includes identification of the substance and avoidance, which often is quite challenging.

BACKGROUND:Severe asthma (SA) often requires subspecialist management and treatment with biologic therapies and/or maintenance systemic corticosteroids (mSCS). OBJECTIVE:To describe contemporary, real-world biologic and mSCS use among U.S., subspecialist-treated patients with SA. METHODS:CHRONICLE is an ongoing, noninterventional study of U.S. adults with SA treated by allergists/immunologists or pulmonologists. Eligible patients are receiving biologics and/or mSCS or are uncontrolled on high-dosage inhaled corticosteroids with additional controllers (HD ICS+). Biologic and mSCS use patterns and patient characteristics were summarized for patients enrolled between February 2018 and February 2019. RESULTS:Among protocol-eligible patients, 58% and 12% were receiving biologics and mSCS respectively, with 7% receiving both. Among 796 enrolled, most were female (67%), non-Hispanic white (71%), of suburban residence (50%), and had elevated body mass index (median 31). Respiratory and nonrespiratory comorbidities were highly prevalent. With biologics (n=557), 51% were anti-IgE and 48% were anti-IL5/IL-5Rα; from May 2018, 76% of initiations were anti-IL-5/IL-5Rα. In patients receiving mSCS, median prednisone-equivalent daily dose was 10 mg. Multivariate logistic regression demonstrated patients of hospital clinics, sites with fewer nonphysician staff, and with a recorded concurrent chronic obstructive pulmonary disease diagnosis were less likely to receive biologics and more likely to receive mSCS. CONCLUSION/CONCLUSIONS:In this real-world sample of U.S., subspecialist-treated patients with SA not controlled by HD ICS+, mSCS use was infrequent and biologic use was common, with similar prevalence of anti-IgE and anti-IL-5/IL-5Rα biologics. Treatment differences associated with patient and site characteristics should be investigated to ensure equitable access to biologics and minimize mSCS use.

Contact dermatitis (CD) is a common skin condition caused by contact with an exogenous agent that elicits an inflammatory response. While history and physical exam can be helpful in distinguishing between irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD), the gold standard for diagnosing ACD is patch testing. While the actual patch test (PT) procedure and application is relatively straightforward, the decisions involving which allergens to use, interpretation of results, determination of relevant allergens and subsequent patient management requires more skill and expertise. Often, the distribution of the presenting dermatitis can provide insight into the potential causative allergens and should be taken into account when selecting PT allergens. Commercially available PT panels and personal care products can be used for patch testing. Determining the clinical relevance of PT results is a critical component of the PT procedure. Patients must be educated on avoidance of relevant allergens and given guidance on alternative products available for use. Special populations, including children with ACD, occupational contact dermatitis (OCD), and patients with biomedical devices have unique allergen considerations and PT panels should be directed as such to address all potential allergens.

Rationale: Cutaneous, inhaled, intranasal and systemic corticosteroids(CS) are commonly prescribed for the treatment of atopic dermatitis(AD), asthma, and allergic rhinitis. The cumulative burden of these steroids in individual patients are not routinely assessed by providers and can lead to adverse effects. We sought to use an EMR-tool to increase documentation of the total steroid burden(SB) in our patients with atopic dermatitis and asthma.
Method(s): A SB EMR-tool was used for 99 AD encounters and 64 asthma encounters over an 18-month period. Data collected included corticosteroid type, potency, frequency, side effects, interventions and counseling.
Result(s): There were 99 AD encounters assessed in 58 patients(53% female, mean age of 31). Of these 99 encounters using topical corticosteroids(TCS), 24 were using inhaled CS; 12 using intranasal CS and 8 using systemic CS. The most common side effects encountered while on TCS included: pigment changes(n=20), skin atrophy(n=11), easy bruising(n=7), telangiectasias(n=6), striae(n=6), rosacea(n=3), and hair growth(n=2). Twenty-eight encounters(28%) had an intervention: 10 decreased dose, 3 decreased potency and 15 discontinued TCS. 85 encounters(86%) documented patient counseling. There were 64 asthma encounters assessed in 49 patients(63% female, mean age of 56). Of these 64 encounters using inhaled CS, 27 were using intranasal CS and 18 using systemic CS. The most common side effects encountered while using inhaled CS included: candidiasis(n=6) and hoarseness(n=1). Four encounters(6.25%) had an intervention: 3 decreased dose, 1 discontinuation. 62 encounters(97%) documented patient counseling.
Conclusion(s): Using our EMR-tool facilitates the identification and tracking of total SB in patients, associated side effects and leads to meaningful intervention.
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BACKGROUND:Structured patient-reported outcomes of AD severity are not standardized in clinical practice. We sought to determine the construct validity, internal consistency, cross-cultural validity, floor or ceiling effects of multiple AD severity assessments. METHODS:A cross-sectional, population-based study of 2893 adults, including 602 adults that met a modified UK Diagnostic Criteria for AD. AD severity was assessed using self-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Scoring AD (PO-SCORAD) and its objective and subjective components, and numerical rating scale (NRS)-itch. QOL was assessed using short-form (SF-)12 mental and physical health scores, SF-6D health utility scores, Dermatology Life Quality Index (DLQI). Hospital Anxiety and Depression Scale (HADS) was assessed. RESULTS:PO-SCORAD, PO-SCORAD objective and subjective sub-scores, NRS-itch and POEM all had moderate to strong correlations with each other, and DLQI, fair to moderate correlations with HADS-A and HADS-D, and inverse correlations with SF-12 MCS and SF-6D (Pearson correlations, P<0.0001). All scores showed good criterion validity as judged by analysis of variance and receiver operator characteristics. PO-SCORAD, PO-SCORAD objective sub-scores and POEM had similarly good internal consistency (Cronbach's alpha=0.84, 0.82 and 0.86); PO-SCORAD subjective sub-score was less internally consistent (alpha=0.57). All scores showed potentially poor cross-cultural validity as demonstrated by uniform and non-uniform differential item functioning by age, sex and/or race/ethnicity for multiple items. There were floor effects for POEM, but not for the other assessments CONCLUSIONS: PO-SCORAD, PO-SCORAD objective and subjective sub-scores, NRS-itch and POEM appear to be valid for assessing AD severity in clinical practice.