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Abstract Interleukin 12 (IL-12) is an important cytokine produced by a variety of immune effector cells that leads to a type 1 helper T cell (Th1) response. IL-12 also directs [...]

Background: Itch and sleep disturbance due to itch are burdensome symptoms associated with atopic dermatitis (AD). Rapid onset of action is important for AD treatments to improve quality of life and relieve suffering. Objectives: This subanalysis evaluated how quickly baricitinib 1-mg and 2-mg reduced itch and associated sleep disturbance during the first 7 days after treatment initiation in a phase 3, double-blind, placebo-controlled trial. Methods: Adult patients with AD were randomized 1:1:1 to placebo (N = 147), baricitinib 1 mg (N = 147) or baricitinib 2 mg (N = 146). Patients kept daily diaries, completing the Itch Numeric Rating Scale (NRS) (itch severity from 0 = no itch to 10 = worst itch imaginable) and the Atopic Dermatitis Sleep Scale (ADSS) to measure sleep disturbance (number of nighttime awakenings because of itch). Mixed model repeated measures analysis was used to analyze change from day 1 to day 7 values. Results: Patients receiving either dose of baricitinib had a 9.9% decrease in itch NRS scores from baseline to Day 2 vs 1.5% decrease for placebo (significant between-group least squares mean [LSM] difference: 8.3; 95% CI −12.66 to −3.89; P =.0002). Baricitinib 2 mg reduced nighttime awakenings due to itch (ADSS item 2) at day 2 by 25.2% vs 3.9% in the placebo group (between-group LSM difference: −21.4, P =.0025). Baricitinib 2 mg continued to demonstrate a statistically significant difference from placebo in sleep symptoms at day 7 (LSM difference −23.9; P =.001). Conclusions: Baricitinib 2-mg provided relief from itching and sleep disturbance in patients with AD, beginning the day after taking first dose. Clinical trials at www.clinicaltrials.gov: BREEZE-AD5 (NCT03435081) [ABSTRACT FROM AUTHOR]

Introduction & Objectives: Janus kinase (JAK) inhibition is a promising approach for the treatment of vitiligo. Here, we report the clinical efficacy and safety of upadacitinib (UPA), an oral JAK inhibitor, in a phase 2b multicenter, randomized, double-blind, placebo-controlled study of adults with extensive non-segmental vitiligo (NSV). Materials & Methods: Eligible patients were aged 18-65 years with NSV, a Facial Vitiligo Area Scoring Index (F-VASI) of ≥0.5, and a Total Vitiligo Area Scoring Index (T-VASI) of ≥5 at baseline. This 52-week study (NCT04927975) comprised 2 periods. In period 1, patients were randomly assigned to once daily UPA 22 mg (UPA22), UPA 11 mg (UPA11), UPA 6 mg (UPA6), or placebo (PBO) for 24 weeks of treatment. In a 28-week blinded extension (period 2), patients receiving UPA during period 1 continued their respective regimens; patients who received PBO in period 1 were pre-assigned to either UPA11 or UPA22. Clinical efficacy endpoints evaluated through week 36 included percent change from baseline (%CFB) in F-VASI (week 24, primary endpoint), reductions from baseline in F-VASI of ≥50% (F-VASI 50) and ≥75% (F-VASI 75), %CFB in T-VASI, and reduction from baseline in T-VASI of ≥50% (T-VASI 50). Safety data as of January 13, 2023 (data cutoff date) are presented. Results: Of the 185 patients enrolled in period 1, 165 (89.2%) continued to period 2. At baseline, 68% of patients had extensive vitiligo (T-VASI > 10), and 71% had active vitiligo. At week 24, the %CFB in F-VASI was greater with UPA11 (-35.6%) and UPA22 (-34.0%) vs PBO (-14.4%; nominal P = .005 and P = .013, respectively). A greater proportion of patients achieved F-VASI 50 and F-VASI 75 with UPA11 (38.3%, 19.1%) and UPA22 (39.5%, 14.0%) vs PBO (10.9%, 2.2%; nominal P < .05 for both doses and for both endpoints). Likewise, the %CFB in T-VASI was greater with UPA11 (-17.3%) and UPA22 (-20.7%) vs PBO (-6.4%; nominal P = .026 and P = .005, respectively). A higher percentage of patients achieved T-VASI 50 with UPA22 (11.6%) than with PBO (2.2%; nominal P = .027). UPA efficacy continued to improve through week 36, with %CFB in F-VASI for UPA6, UPA11, and UPA22 of -20.8%, -44.9% and -47.7%, respectively. At week 36, F-VASI 50 was achieved with UPA6, UPA11, and UPA22 by 34.2%, 54.3% and 61.5% of patients and F-VASI 75 by 15.8%, 40.0%, and 30.8%, respectively. At week 36, %CFB in T-VASI for UPA6, UPA11 and UPA22 were -24.3%, -32.0% and -37.6%, with 10.5%, 20.0% and 19.2% of patients, respectively, achieving T-VASI 50. Treatment-emergent adverse event (TEAE) rates were generally similar with UPA and PBO in period 1 (most common TEAEs: COVID-19, acne, fatigue, and headache) and were similar across treatment arms in period 2. One death adjudicated as undetermined/unknown cause and deemed by the investigator to have no reasonable possibility of being related to study drug occurred in the UPA22 group (period 1). One adjudicated event of nonfatal ischemic stroke occurred with UPA11 (period 2). There were no adjudicated events of venous thromboembolism, gastrointestinal perforation, or events of opportunistic infection, active tuberculosis, or malignancy. Conclusion: Treatment with UPA for 24 weeks resulted in greater improvements vs PBO in the clinical outcomes of adults with extensive NSV. Observed clinical efficacy continued to improve through week 36 with UPA treatment. UPA was generally well tolerated, with no new safety signals identified. [ABSTRACT FROM AUTHOR]

Introduction & Objectives: Vitiligo has a considerable negative impact on patients' health-related quality of life (HRQoL). Patients often experience social stigma, low self-esteem, anxiety, and depression. Assessment of HRQoL is therefore recommended as part of the evaluation of disease severity and treatment benefits. Accordingly, the impacts of treatment with upadacitinib (UPA), an oral Janus kinase inhibitor, on a range of patient-reported HRQoL outcomes were evaluated as part of a phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-ranging study in adults with non-segmental vitiligo. Materials & Methods: Adults aged 18-65 years with non-segmental vitiligo with a Facial Vitiligo Area Scoring Index score =0.5 and a Total Vitiligo Area Scoring Index score =5 at baseline were included in this 52-week study (NCT04927975). During a 24-week, double-blind, placebo-controlled treatment period (period 1), patients were randomly assigned to receive UPA 6 mg (UPA6), UPA 11 mg (UPA11), UPA 22 mg (UPA22), or placebo once daily (QD). Patient-reported HRQoL outcomes assessed at the week 24 primary analysis timepoint (ie, end of period 1) included change from baseline in vitiligo QoL (VitiQoL) total score (lower scores reflect better HRQoL), achievement of a Vitiligo Noticeability Scale (VNS) response of 4 ("a lot less noticeable") or 5 ("no longer noticeable"), change from baseline in Dermatology Life Quality Index (DLQI; lower scores reflect better HRQoL), change from baseline in Hospital Anxiety and Depression Scale (HADS) anxiety and depression scores (where lower scores reflect less anxiety and/or depression), and achievement of a Patient's Global Impression of Change-Vitiligo (PaGIC-V) response of 1 ("much better") or 2 ("a little better"). Results: A total of 185 patients were enrolled in the study (UPA6 n=49; UPA11, n=47; UPA22, n=43; placebo n=46). Mean reductions in VitiQoL scores from baseline to week 24 with UPA22 (-6.6) and UPA6 (-7.5) were numerically larger than with placebo (-5.5), although not statistically significant. At week 24, more patients treated with UPA22 reported a VNS response of "a lot less noticeable" or "no longer noticeable" than with placebo (11.6% vs 0%, respectively; P < .05). Mean reductions in DLQI scores from baseline to week 24 were significantly larger with UPA22 than with placebo (-2.2 vs -0.6; P < .05). HADS anxiety scores decreased from baseline to week 24 in the UPA6 and UPA22 groups, with similar reductions in HADS depression scores observed for the UPA11 and UPA22 groups; changes in HADS scores were not significantly different vs placebo. A significantly greater proportion of patients achieved a PaGIC-V response of "much better" or "a little better" with any UPA dose vs placebo: UPA6 (34.7%), UPA11 (55.3%), and UPA22 (60.5%) vs placebo (19.6%; P < .05 vs placebo for all UPA doses). Conclusion Among adults with non-segmental vitiligo, 24 weeks of treatment with UPA at all doses resulted in improvements compared to placebo in patient impressions of disease improvement based on PaGIC results. These initial findings suggest that UPA22 may improve patient HRQoL and perceptions of vitiligo noticeability; longer term data from the extension phase of this study will further clarify the impact of UPA treatment on QoL. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is a chronic disease affecting children and adults and requires long-term treatment. Moderate-to-severe AD causes itching, which considerably impacts sleep. Interleukin (IL)-13 is the key cytokine in the skin of patients with AD. Lebrikizumab (LEB) is a novel monoclonal antibody that binds with high affinity and slow off-rate to IL-13, thereby blocking the downstream effects of IL-13 with high potency. LEB has demonstrated efficacy and maintained improvement in measures of itch and sleep over 52 weeks in previous phase 3 trials. ADhere (NCT04250337) was a 16-week, randomized, double-blinded, placebo-controlled, phase 3 clinical trial, where patients were treated with LEB and topical corticosteroids (TCS) vs placebo and TCS. LEB responders from ADhere at week 16 were defined as having Investigator's Global Assessment response of 0 or 1 or reporting 75% improvement from ADhere baseline in Eczema Area and Severity Index who did not use rescue medications. ADhere LEB responders were rerandomized 2:1 into ADjoin (NCT04392154) for blinded treatment with LEB 250 mg every 2 weeks (Q2W) or every 4 weeks (Q4W), respectively, with TCS use as needed, for an additional 100 weeks with itch and sleep data being collected for the first 52 weeks. Objectives: The objectives of the study are to report the impact of LEB on itch and sleep improvements over a longer period (68 weeks) in ADhere week 16 LEB responders with moderate-to-severe AD who entered a long-term extension study, ADjoin. Methods: Itch was reported using the Pruritus Numeric Rating Scale (NRS), a patient-reported, single-item, daily, 11-point scale, where the minimal clinically important difference (MCID) is 3 points. Sleep loss due to itch was reported using the Sleep-Loss Scale, a patient-reported, single-item, 5-point scale, where the MCID is 1 point. We report =3-point improvement in Pruritus NRS among patients with baseline score at least 3, percent change from ADhere baseline (PCFB) in Pruritus NRS, Pruritus NRS (0,1), =1-point improvement in Sleep-Loss Scale score among patients with baseline score at least 1, =2-point improvement in Sleep-Loss Scale score among patients with baseline score at least 2 and PCFB in Sleep-Loss Scale score. All outcomes were reported at week 52 of ADjoin study, after a total of 68 weeks of LEB treatment. As observed analyses used all data collected. Results: At week 68, most patients reported maintaining ≥3-point improvement in Pruritus NRS treated with LEB Q2W (80.6%, 29/36) and LEB Q4W (88.9%, 16/18). Patients treated with LEB Q2W and LEB Q4W reported maintaining 65.3% and 59.4% improvement in Pruritus NRS at week 68 compared to ADhere baseline, respectively. At week 68, 45.9% (17/37) patients in LEB Q2W group and 31.6% (6/19) in LEB Q4W group reached Pruritus NRS of 0 or 1. At week 68, most patients reported maintaining ≥1-point improvement in Sleep-Loss Scale score treated with LEB Q2W (96.9%, 31/32) and LEB Q4W (85.7%, 12/14). Similarly, most patients reported maintaining ≥2-point improvement in Sleep-Loss Scale score treated with LEB Q2W (60.9%, 14/23) and LEB Q4W (75.0%, 6/8). Patients treated with LEB Q2W and Q4W reported maintaining 84.1% and 58.8% improvement in Sleep-Loss Scale score at week 68, respectively, compared to ADhere baseline. Conclusions: LEB + TCS maintained itch and sleep improvement at 68 weeks in patients with moderate-to-severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

This study assesses distress and anxiety symptoms associated with quarantine due to COVID-19 exposure among the first quarantined community in the United States and identifies potential areas of intervention. All participants were directly or peripherally related to "patient 1,"—the first confirmed community-acquired case of COVID-19 in the New York Area. As such, this is a historically significant sample whose experiences highlight a transitional moment from a pre-pandemic to a pandemic period in the United States. In March 2020, an anonymous survey was distributed to 1,250 members of a NYC area community that was under community-wide quarantine orders due to the COVID-19 outbreak. Distress was measured using the Subjective Units of Distress Scale (SUDS) and symptoms of anxiety were measured using the Beck Anxiety Inventory (BAI). A variety of psychosocial predictors relevant to the current crisis were explored. Three hundred and three individuals responded within forty-eight hours of survey distribution. Mean levels of distress in the sample were heightened and sustained, with 69% reporting moderate to severe distress on the SUDS and 53% of the sample reported mild, moderate, or severe anxiety symptoms on the BAI. The greatest percentage of variance of distress and anxiety symptoms was accounted for by modifiable factors amenable to behavioral and psychological interventions. [ABSTRACT FROM AUTHOR]

At one time considered opposing diseases, it is now recognized that atopic dermatitis (AD) and psoriasis can coexist. There are limited data characterizing this population of patients. In this study, we characterize the population of patients diagnosed with both AD and psoriasis and summarize their response to therapy. A retrospective chart review was performed and data was recorded for patients with a diagnosis of psoriasis (n = 1390), AD (n = 912) and psoriasis plus AD (n = 30) within the Tufts Medical Center Department of Dermatology between January 1, 2012 and May 1, 2019. The prevalence of concomitant AD and psoriasis was 1.5%. Of those with both AD and psoriasis, hand involvement was high (63%). Systemic therapy was used in 73% of patients. Of those on biologics, 30% required more than one biologic consecutively and 22% required more than one biologic simultaneously to achieve clinically significant results. Patients with overlapping AD and psoriasis have a high prevalence of hand involvement, poor response to topical therapy, and may require multiple systemic agents to treat. In a patient with known history of psoriasis with recalcitrant hand disease involvement, AD should be considered. [ABSTRACT FROM AUTHOR]

Vitiligo is an autoimmune skin depigmenting disorder that can negatively impact quality of life. A new FDA approved treatment for vitiligo offers considerable promise, and to maximize benefits strategies to implementation should consider disease burden, healthcare access, and healthcare utilization of individuals with vitiligo. Using the All of Us Research Program’s large data set, including survey responses, we investigated these outcomes among participants with and without vitiligo. Our analysis used quality of life, delayed care due to an obstacle, and seeing a doctor in the past year as dichotomized proxies for disease burden, healthcare access, and healthcare utilization. The results show that people with vitiligo are more likely to report worse quality of life but ostensibly greater healthcare access and utilization compared to people without vitiligo. However, these relationships are not significant when adjusted for demographics, socioeconomic characteristics, and comorbidities of vitiligo. Prior research has shown non-Caucasian individuals have worse health outcomes in general, and worse quality of life within the vitiligo population. Our data demonstrated consistent findings; moreover, we found that non-Caucasian individuals with vitiligo had inferior healthcare access and lower health care utilization than Caucasian individuals. Implementation of new treatments for vitiligo should prioritize disadvantaged individuals to improve health equity. [ABSTRACT FROM AUTHOR]

ABSTRACT A 61-year-old-female with a 4-year history of disseminated granuloma annulare was successfully treated with the antitumor necrosis factor (TNF)-alpha antibody, adalimumab. The patient had failed high potency topical glucocorticoids, [...]

Dermatitis herpetiformis (DH) is a rare autoimmune blistering disorder in which patients with celiac disease, a gluten-sensitive enteropathy, present with a severely pruritic papulovesicular eruption over extensor surfaces such as the knees, elbows, lower back, buttocks, and neck. Patients are instructed to adhere to a gluten-free diet for purposes of improving their skin disease and gluten-sensitive enteropathy; this is the only treatment that lowers risk of enteropathy-associated T cell lymphoma. Patients who adhere to a strict gluten-free diet often have remission of their skin disease over months to years. Dapsone is a rapid and extremely effective first-line treatment option and often used while transitioning to a gluten-free diet. Aside from gluten-free diet and dapsone, second-line treatment options include sulfapyridine, sulfasalazine, and colchicine. Some patients have difficulty adhering to a gluten-free diet or develop intolerable side effects to systemic therapies. Furthermore, there is limited data on the use of the second-line treatments. Recent studies have shed light on the role of JAK-STAT-dependent pathways in the pathogenesis of dermatitis herpetiformis. We present a patient treated with tofacitinib, 5mg twice daily, an oral JAK1/3 inhibitor, who demonstrated clinical improvement of DH and control of new lesion development. [ABSTRACT FROM AUTHOR]

Introduction: Burdensome symptoms of atopic dermatitis include itch and sleep disturbance. This post hoc analysis reports the effect of baricitinib on itch and sleep disturbance during the first week of treatment in 3 phase 3 studies. Methods: Patients were randomized 2:1:1:1 to once-daily placebo or baricitinib 1 mg, 2 mg, or 4 mg in the BREEZE-AD1 and -AD2 studies and 1:1:1 to once-daily placebo or baricitinib 2 mg or 4 mg in the BREEZE-AD7 study. Topical corticosteroids were only allowed in BREEZE-AD7. Patients completed the itch numerical rating scale and atopic dermatitis sleep scale (ADSS) items 1–3 using an electronic daily diary. Data were analyzed by study as least squares mean percent change from baseline in daily scores for the randomized patients. Mixed model repeated measures analysis was used to analyze change from baseline values. Results: A total of 624, 615, and 329 patients were randomized in BREEZE-AD1, -AD2, and -AD7, respectively. Itch severity significantly improved with baricitinib 2 mg and 4 mg versus placebo starting at day 2 (1 day after first dose) in BREEZE-AD1 and -AD7 and at day 1 in BREEZE-AD2. Patients' ability to fall asleep (ADSS item 1) significantly improved with baricitinib 2 mg and 4 mg versus placebo starting at day 2 in all three studies. There were significant improvements in patients waking due to itch (ADSS item 2) with baricitinib 4 mg versus placebo starting at day 2 in all three studies. Patients' ability to return to sleep after being woken by itch (ADSS item 3) was significantly improved with baricitinib 4 mg versus placebo starting at day 2 in BREEZE-AD1 and -AD2 and at day 4 in BREEZE-AD7. Conclusion: Rapid onset of action, typically 1 day after taking the first dose of baricitinib, was observed consistently for the burdensome symptoms of itch and sleep disturbance. ClinicalTrials.gov identifiers: BREEZE-AD1, NCT03334396; BREEZE-AD2, NCT03334422; BREEZE-AD7, NCT03733301. [ABSTRACT FROM AUTHOR]