Jensen C. Yeung

Background: Evaluating the real-world effectiveness, safety, and tolerability of targeted biologic and non-biologic therapies in patients with atopic dermatitis (AD) treated in routine clinical practice remains crucial. In this international, multicenter, retrospective, comparative study we aimed to evaluate the 52-week effectiveness, safety, and tolerability of dupilumab, tralokinumab, and upadacitinib in patients with AD aged ≥ 12 years. Methods: Effectiveness was assessed at weeks 16, 24, and 52 using Eczema Area and Severity Index (EASI) and itch Numerical Rating Scale (NRS) scores. Safety was measured via adverse events (AEs). Results: A total of 1286 treatment courses were included: 62.5% received dupilumab, 24.3% received upadacitinib, and 13.1% received tralokinumab. Upadacitinib demonstrated higher effectiveness than dupilumab and tralokinumab across all time points and most evaluated outcomes both on the overall population and the biologic-/JAKi-naïve population, including stringent treatment targets such as EASI 90 response and combined EASI 90 + itch NRS 0/1 response. While upadacitinib demonstrated superior effectiveness, it was associated with a higher incidence of AEs, both leading to and not leading to treatment discontinuation, including thromboembolic events, lipid abnormalities, and hematologic abnormalities. In contrast, conjunctivitis was the most frequently observed AE among patients receiving biologics. Conclusions: This study provides a comprehensive real-world comparison of dupilumab, tralokinumab, and upadacitinib in AD, highlighting upadacitinib's superior effectiveness in achieving stringent treatment targets, both in the short and long term, but also a higher incidence of AEs. However, the considerable heterogeneity of the study population, an inherent limitation of real-world studies, must be acknowledged when interpreting these findings.

Varying hair textures and hair care practices contribute to nuances in clinical presentation and management of scalp psoriasis across diverse patient populations. Cohort B of the VISIBLE trial enrolled participants with moderate to severe scalp psoriasis and skin of color, across the skin-tone spectrum. To evaluate efficacy, quality of life, and adverse event outcomes of guselkumab, 100 mg, among participants with moderate to severe scalp psoriasis and skin of color over 48 weeks. This ongoing phase 3b, randomized clinical trial at 45 sites in the US and Canada enrolled adults with skin of color and moderate to severe scalp psoriasis (scalp surface area [SSA] ≥30%; Psoriasis Scalp Severity Index [PSSI] ≥12; scalp-specific Investigator's Global Assessment [ss-IGA] score ≥3; ≥1 nonscalp plaque). Data were collected from September 2022 to June 2024. Randomized participants (3:1) received guselkumab, 100 mg, at weeks 0, 4, and every 8 weeks, or placebo at weeks 0, 4, and 12, then guselkumab at weeks 16, 20, and every 8 weeks. Coprimary end points were ss-IGA score of 0 or 1 (ss-IGA 0/1) and 90% or greater improvement in PSSI (PSSI 90) at week 16 (guselkumab vs placebo). Major secondary end points included ss-IGA 0 (complete scalp clearance), PSSI 100, percentage changes from baseline in PSSI and SSA, changes from baseline in Dermatology Life Quality Index (DLQI) and Psoriasis Symptoms and Signs Diary (PSSD) symptoms score, and 4-point or greater reduction in Scalp Itch Numeric Rating Scale (NRS) score. Of 108 participants (81 randomized to guselkumab; 27 randomized to placebo), 100 (92.6%) completed 48 weeks of treatment. The mean (SD) age overall was 42.5 (13.6) years, and 58 participants (56.9%) were male. At the week 16 primary end point, in the guselkumab (n = 76) vs placebo (n = 26) groups, respectively, response rates were as follows: ss-IGA 0/1, 68.4% (n = 52) vs 11.5% (n = 3) (P < .001); PSSI 90, 65.8% (n = 50) vs 3.8% (n = 1) (P < .001); ss-IGA 0, 57.9% (n = 44) vs 3.8% (n = 1) (P < .001); PSSI 100, 59.2% (n = 45) vs 3.8% (n = 1) (P < .001); 4-point or greater reduction in Scalp Itch NRS score (in those with a baseline score of at least 4), 69.4% (n = 50 of 72) vs 24.0% (n = 6 of 25) (P < .001). Guselkumab efficacy increased and was maintained through week 48, when guselkumab-randomized participants achieved mean (SD) percentage improvements in PSSI and SSA of 94.6% (12.2%) and 94.8% (16.2%), respectively, and 51 (67.1%) achieved ss-IGA 0. DLQI and PSSD symptoms score least-squares mean changes were -9.7 (95% CI, -11.1 to -8.2) vs -2.2 (95% CI, -4.8 to 0.4) (P < .001) and -44.8 (95% CI, -50.6 to -39.1) vs -8.3 (95% CI, -18.4 to 1.9) (P < .001), respectively, with sustained improvements through week 48. Through week 16, infections were the most common adverse events in the guselkumab (n = 12; 14.8%) and placebo (n = 1; 3.7%) groups. In this randomized clinical trial, after 3 doses of guselkumab, most participants achieved significant scalp clearance and clinically meaningful quality-of-life improvements; improvements increased and were maintained through week 48. ClinicalTrials.gov Identifier: NCT05272150.

Background: Atopic dermatitis (AD) is a highly prevalent disease in Canada with significant patient burden. Treatment guidance for topical therapy (the mainstay of AD management), with particular consideration of emerging treatments, may further improve patient care. Here, we aim to provide healthcare professionals with AD treatment recommendations from the perspective of 10 Canadian dermatologists with expertise in managing AD. Methods: The panel of dermatologists conducted a systematic literature review and leveraged their clinical experience to develop generally accepted principles, consensus statements, and a treatment algorithm using an iterative consensus process. Results: The panel collectively developed six generally accepted principles, 10 consensus statements, and a treatment algorithm. The guidance notes that assessment of disease severity should encompass both physician-rated measures and patient-reported outcomes. Disease education, lifestyle-based strategies (e.g., trigger avoidance), and supportive measures (e.g., moisturizers) can help reduce signs and symptoms of AD. Choice of therapy should consider disease-, patient-, and treatment-related factors. Although topical corticosteroids (TCS) are often used as first-line treatment in AD, they should be limited to intermittent short-term use. Noncorticosteroid topical therapies (e.g., topical calcineurin inhibitors; topical phosphodiesterase-4 inhibitors; and topical Janus kinase inhibitors) can be used for widespread involvement of AD according to approved use. Once treatment goals are achieved, noncorticosteroid topical maintenance therapy should continue to prevent flares and reduce the need for TCS. Conclusions: Guidance reflecting the benefits and limitations of topical AD treatments in conjunction with patient understanding of treatment goals supports robust shared decision-making in the management of AD.

Background: Untreated sympathetic blockade after spinal anaesthesia for caesarean delivery can cause profound maternal hypotension. National Institute for Health and Care Excellence (NICE) guidance recommends systolic blood pressure (SBP) should be maintained ≥90% of the baseline. This multi-centre audit assessed compliance with guidance regarding choice and administration method of vasopressors during caesarean delivery under spinal anaesthesia. Methods: A multi-centre prospective audit of adult patients undergoing caesarean delivery under spinal anaesthesia was undertaken across the West Midlands, UK. Anonymised patient data was obtained during routine peri-operative care and audited across primary, process and clinical outcomes. The primary audit outcome was maintenance of intra-operative SBP at ≥90% baseline. Results: Five-hundred-and-twenty-six patients were included. The primary outcome was achieved in 9.1% of cases. SBP was maintained within 80-90% of baseline in 65.0%, and below 80% of baseline in 25.9%. Phenylephrine was the first-line vasopressor in 91% of cases, administered via a rate-controlled device in 73.8%. Compliance with the international consensus recommendation for prophylactic phenylephrine via a rate-controlled device at 25-50 μg/min was 37.6%. Clinician-reported incidence of intra-operative nausea and vomiting were 24.9% and 8.4% respectively. Secondary analysis found that use of rate-controlled pump devices to administer prophylactic vasopressors was associated with reduced incidence of SBP decrease to <80% of baseline (P <0.01). Conclusions: Intraoperative hypotension is common, and there is lack of adherence to guidance, including variation in choice and administration method of prophylactic vasopressors. Optimal management of hypotension should be incorporated into departmental guidance for enhanced recovery.

There is limited evidence on treating psoriasis patients with skin of color (SOC), contributing to disparities in accessing appropriate care for these patients. This study aimed to develop consensus statements defining SOC terminology and addressing needs to optimize the clinical management of psoriasis in patients with SOC. Using the modified Delphi methodology 16 Canadian dermatologists with expertise in psoriasis developed consensus statements. Four core faculty members drove the content of the study, and 12 additional panel members were consulted to vote and provide consensus on the content produced by the core faculty. At a final meeting, the full panel revised and voted on the final consensus statements. The exercise resulted in 11 consensus statements on SOC terminology, as well as 5 primary and 4 secondary statements on clinical presentation and differential diagnosis, and treatment guidelines based on evidence and expert opinion. Four additional consensus statements on current assessment tools and access to care were developed based solely on expert opinion. The available evidence was limited, low quality, and inappropriate for formal quality assessment. The consensus statements developed in this study may provide valuable guidance to the dermatology community treating psoriasis patients with SOC.