Faculty Bibliography

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

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

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.