Introduction & Objectives Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with comorbidities, including major adverse cardiovascular (CV) events (MACE), venous thromboembolism (VTE), and malignancy (excluding nonmelanoma skin cancer [exNMSC]). Incidence of MACE, VTE, and malignancy (exNMSC) was comparable to or lower than background rates reported in US AD population. We evaluated long-term incidence rates of MACE, VTE, and malignancy (exNMSC) by CV risk category among patients with AD with up to 6 years of UPA treatment. Materials & Methods Data were pooled from the phase 3, randomized, double-blind, multicenter, placebo-controlled Measure Up 1 & 2 (NCT03569293, NCT03607422) and AD Up (NCT03568318) trials. AD patients were randomized 1:1:1 to once-daily oral UPA 15 mg, UPA 30 mg, or placebo. After the 16-week double-blind treatment period, patients receiving UPA continued their assigned treatment, while patients treated with placebo were rerandomized 1:1 to UPA 15 mg or 30 mg. Incidence rates for MACE (CV death, nonfatal myocardial infarction, or nonfatal stroke), VTE (deep vein thrombosis or pulmonary embolism [fatal and nonfatal]), and malignancy (exNMSC) were evaluated as exposure-adjusted incidence rates per 100 patient-years (n/100 PY). MACE, VTE, and malignancy (exNMSC) background rates in the general US AD population were assessed in a retrospective observational claims-based analysis from Optum’s deidentified Clinformatics Data Mart database; this real-world reference population included patients with an AD diagnosis during the study period (March 2017–September 2024) determined by International Classification of Diseases 9th or 10th edition codes (≥ 1 inpatient or ≥ 2 outpatient claims for AD), and age restrictions from the UPA studies (12–75 years) were implemented. Background rates were weighted to mimic the age and sex distribution in the combined UPA trial population. Cohort stratification was based on the presence of CV risk factors at baseline (0 vs ≥ 1); UPA phase 3 data were further stratified by 1 vs 2 CV risk factors. CV risk factors included prior CV event, hypertension, diabetes mellitus, tobacco/nicotine use (current and former), elevated low-density lipoprotein cholesterol, or lowered high-density lipoprotein cholesterol. Results 2683 UPA-treated patients were included (UPA 15 mg, n = 1337, PY = 4435.2; UPA 30 mg, n = 1346, PY = 4752.5). MACE, VTE, and malignancy (exNMSC) background rates from the claims-based study were evaluated in 50,447 patients with AD. Long-term incidence rates in patients with up to 6 years of UPA treatment were low for MACE and VTE (all ≤ 0.2 n/100 PY) and malignancy (exNMSC; all ≤ 0.7 n/100 PY) and similar for patients who had 0 vs ≥ 1 CV risk factor. Rates from UPA phase 3 studies were similar to real-world US incidence rates in patients with AD. Rates remained low when UPA-treated patients were stratified by 1 vs 2 CV risk factors. Conclusion Incidence rates of MACE, VTE, and malignancy (exNMSC) in patients with moderate-to-severe AD who received up to 6 years of UPA treatment remained low and consistent with those observed in the overall population of patients with AD, regardless of CV risk category.
Introduction The Psoriasis Longitudinal Assessment and Registry (PSOLAR; NCT00508547) is a large, international, prospective, longitudinal, disease-based registry that enrolled patients with psoriasis (PsO) who were receiving, or were candidates for, systemic therapy. The aims of the Registry are to assess the long-term safety and improve understanding of real-world biologic use in patients with PsO. Objective The objective of this analysis is to describe real-world effectiveness of guselkumab in patients with psoriasis. Methods Disease characteristics, absolute Psoriasis Area and Severity Index (PASI) score, percentage of body surface area (BSA) involvement, and change from baseline in PASI score and BSA through two years are reported for patients with PsO treated with guselkumab (GUS). Some patients initiated GUS ahead of enrolment in the registry. Results As of 12 July 2024, 2198 patients who initiated GUS prior to, or at, enrolment were included with a mean (standard deviation [SD]) duration of follow-up of 3.02 (1.08) years. Of these, 1184 (53.9%) were from North America, 672 (30.6%) were from Europe and 342 (15.6%) were from the Asia-Pacific region. Through 2 years of treatment, 244 (11.1%) patients withdrew from the registry, with the most common reason for withdrawal being patient choice (n=96, 39.3%) and 48 (19.7%) patients being lost to follow-up. Most patients had plaque PsO (2140, 97.4%) with a mean (SD) baseline PASI score of 6.0 (7.02) and a mean (SD) BSA involvement of 8.9% (12.72%). At baseline, 427 (21.1%) patients had a PASI score of 0, 188 (9.3%) had PASI >0–<1, 199 (9.8%) had PASI ≥1–<2, 160 (7.9%) had PASI ≥2–<3, 231 (11.4%) had PASI ≥3–<5 and 816 (40.4%) had PASI ≥5. Approximately 1 in 4 GUS patients had a PASI score of >10 (n=496; 24.5%). At Month 6, the mean (SD) change from baseline in PASI score was −4.5 (7.06) and the mean (SD) change from baseline in %BSA was −6.6 (12.41), corresponding to a mean (SD) absolute PASI score of 1.6 (3.10) and a mean (SD) BSA of 2.3% (5.81%), respectively. Improvements were maintained through 1 year of therapy; at Month 12, the mean (SD) change from baseline in PASI score was −4.4 (6.96) and in %BSA was −6.8 (12.26), corresponding to mean (SD) absolute PASI score of 1.5 (2.74) and a mean (SD) BSA of 1.9% (4.79%). Improvements were maintained through 2 years of treatment, with a mean (SD) absolute PASI score of 1.5 (3.13) and a mean (SD) BSA of 2.1% (6.08%), respectively. Conclusion: Patients in this large real-world registry experienced improvements in PsO severity while receiving treatment with GUS. Improvements were maintained through 2 years of treatment, supporting the use of GUS as a highly effective long-term option for patients with PsO.
Melasma, a challenging pigmentary disorder affecting the face, often poses diagnostic difficulties due to its similarity to numerous other conditions. This study aimed to introduce and evaluate a novel dermoscopic feature, pigmented rings with central clearing (PRCC), in aiding the diagnosis of melasma and distinguishing it from similar conditions.
Introduction & Objectives: Amlitelimab (SAR445229, KY1005) is a fully human, anti-OX40 ligand (OX40L) monoclonal antibody. In the STREAM-AD phase 2b trial (NCT05131477), the primary endpoint was met at Week 16, with a significant decrease in Eczema Area and Severity Index (EASI) percentage change with amlitelimab versus placebo. Amlitelimab demonstrated clinically meaningful improvements in atopic dermatitis (AD) lesions and pruritus compared with placebo-treated participants up to Week 24 in Part 1, including the proportion of patients achieving ≥90% improvement of EASI (EASI-90). In clinical responders, defined as participants achieving EASI-75 and/or Investigators Global Assessment (IGA) 0/1 at Week 24, durability of response (EASI-75 and IGA 0/1) was observed through Week 52 (Part 2), with improvements maintained while participants were either on- or off-amlitelimab. Here, the proportion of clinical responders achieving and maintaining EASI-90 with amlitelimab in Part 2 of the STREAM-AD trial is reported. Materials & Methods: STREAM-AD was a 52-week, randomised, double-blinded, placebo-controlled trial, consisting of a 24-week treatment period (Part 1) and a 28-week maintenance/withdrawal period (Part 2). Adults with moderate-to-severe AD (N=390) were randomised 1:1:1:1:1 to receive subcutaneous amlitelimab every 4 weeks (Q4W; 250 mg + 500-mg loading dose [LD], n=77; 250 mg, n=78; 125 mg, n=77; or 62.5 mg, n=79) or placebo Q4W (n=79) in Part 1. In Part 2, clinical responders (N=190) were re-randomised 3:1 to withdraw from amlitelimab or continue their pre-Week 24 dose (250 mg with 500-mg loading dose, n=34 [treatment withdrawal]/n=13 [continuing]; 250 mg, n=28/n=12; 125 mg, n=33/n=12; 62.5 mg, n=35/n=7; placebo responders continuing placebo, n=16) for 28 weeks. Among overall clinical responders (participants achieving EASI-75 and/or IGA 0/1 at Week 24), the proportion of patients who achieved EASI-90 at Week 24 and maintained it at Week 52 following continuation or withdrawal from amlitelimab during Part 2 (post hoc) was evaluated. Participants using rescue medications in Part 2 or with missing data were imputed as non-responders. Results: Among overall amlitelimab-treated clinical responders, 62.6% achieved EASI-90 at Week 24. Among these Week 24 EASI-90 responders, 61.3% of participants who continued amlitelimab during Part 2 maintained EASI-90 at Week 52. Of the Week 24 EASI-90 responders who withdrew from amlitelimab for 28 weeks, 59.0% maintained EASI-90 at Week 52. Conclusions: The results demonstrate that a high proportion of clinical responders achieved EASI-90 response at Week 24. The majority maintained EASI-90 response with continued amlitelimab treatment at Week 52. Notably, EASI-90 was also maintained at Week 52 after 28 weeks of withdrawal from amlitelimab by the majority of Week 24 EASI-90 responders. Taken together, these data further demonstrate that targeting the OX40L/OX40 pathway via amlitelimab may lead to durable disease control, even while off-amlitelimab, in patients with moderate-to-severe AD. Ongoing phase 3 trials will further evaluate the effect of continued amlitelimab treatment or withdrawal over longer observational periods.
Background: Clinical phenotypes and endotypes of atopic dermatitis (AD) may vary across diverse populations. Although Black or African American patients exhibit a high overall burden of disease, an evidence gap remains in understanding outcomes of advanced therapies in this population. Objectives: To evaluate the efficacy and safety profile of upadacitinib 15 or 30 mg (UPA15 or UPA30, respectively) once daily monotherapy in Black or African American patients with moderate-to-severe AD. Methods: This post-hoc integrated analysis of the Measure Up 1 and 2 phase 3 trials (NCT03569293; NCT03607422) included Black or African American patients randomized to double-blinded oral UPA15, UPA30, or placebo for 16 weeks, with 140-week data included from a blinded extension period (daily UPA15 or UPA30). Optimal treatment targets for skin, itch, and quality of life (QoL) improvement included 90% improvement of Eczema Area and Severity Index (EASI 90), validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 (vIGA 0/1), Worst Pruritus Numeric Rating Scale of 0 or 1 (WP-NRS 0/1), and Dermatology Life Quality Index of 0 or 1 (DLQI 0/1). Minimal disease activity (MDA) was defined as simultaneous achievement of EASI 90 and WP-NRS 0/1. Lichenification was assessed as improved EASI and Scoring Atopic Dermatitis (SCORAD) component scores. Clinically meaningful reduction in Patient-Oriented Eczema Measure (ΔPOEM≥4) and impact of AD on sleep (Atopic Dermatitis Impact Scale Sleep domain; ΔADerm-IS Sleep≥12) were assessed. Non-responder imputation was used in the analysis through week 16 and observed cases at weeks 52 and 140. Adverse events were evaluated through weeks 16 and 140. Results: This analysis included 112 Black or African American patients (UPA15, n=47; UPA30, n=27; placebo, n=38). Demographics were consistent across groups (48.1-61.1% female, mean age 33.2-37.3 years). At week 16, UPA15- and UPA30-treated patients achieved reduction in AD severity and extent (EASI 90: 34.9|57.7%), little-to-no itch (WP-NRS 0/1: 25.6|38.5%), MDA (14.0|34.6%), and no effect on patient’s life (DLQI 0/1: 35.1|34.8%). Patients with moderate-to-severe lichenification demonstrated substantial improvement. Improvements were sustained with long-term treatment. At week 140, 91.7% of UPA15-treated patients achieved EASI 90, 75.0% reported WP-NRS 0/1, 70.8% achieved MDA, and 94.7% experienced clinically meaningful improvement in the impact of AD on sleep. Similar trends were observed for a majority of UPA30-treated patients across most outcome measures. No new safety signals were identified in this racial group. Conclusion: Black or African American patients treated with upadacitinib achieved optimal targets for skin clearance, itch relief, and QoL. The safety profile was consistent with prior studies, confirming upadacitinib is safe and efficacious as a long-term treatment for moderate-to-severe AD in Black or African American patients.
