Search

This article discusses a study that examines the relationship between sun exposure, skin aging, and basal cell carcinoma (BCC). The study used DNA methylation data from sun-exposed and sun-protected skin samples, as well as BCC samples, to analyze epigenetic and biological age, and telomere length. The results show that sun-exposed skin has a slower epigenetic and biological aging process and shorter telomeres compared to sun-protected skin. These effects were more common in older individuals and females. The study suggests that these age dysregulation patterns may indicate an increased risk of skin cancer after prolonged sun exposure. The study was funded by various sources and the authors have no conflicts of interest. [Extracted from the article]

Introduction While clinical trial data demonstrates the efficacy and safety of upadacitinib (UPA), an oral Janus kinase inhibitor (JAKi) for atopic dermatitis (AD), long-term real-world evidence remains limited. Objectives Our study evaluated the real-world effectiveness and safety of UPA for AD at week 52±6. Methods We conducted a multicenter retrospective review of 3 practices in Canada. Effectiveness endpoints were evaluated at weeks 52±6 and including the following: Investigator Global Assessment (IGA) score of clear or almost clear (IGA 0/1) as well as improvements in Eczema Area and Severity Index (EASI), body surface area (BSA), IGAxBSA, and Dermatology Life Quality Index (DLQI)/Children's DLQI (CDLQI). Safety was determined via incidence of treatment-related adverse events (AEs). Results A total of 102 patients with AD were included in the analysis; mean age was 44.2 (range: 12-79) years and 52.9% (54/102) were female. Initial UPA doses were 15 mg (UPA15: 41.2%, 42/102) or 30 mg (UPA30: 58.8%, 60/102) once daily. Previous systemic therapies included conventional non-biologics (72.5%), biologics (30.4%), and JAKi (2.9%). At week 52±6: 78.4% (80/102) of patients achieved Investigator Global Assessment (IGA) 0/1; 87.5% (49/56), 78.6% (44/56), and 50.0% (28/56) achieved Eczema Area and Severity Index (EASI) improvements of 75% (EASI75), 90% (EASI90), and 100% (EASI100), respectively; 75.0% (42/56) achieved EASI90 + IGA 0/1; mean EASI was reduced from 12.9 to 0.8 (mean EASI improvement = 91.4%); 91.9% (52/56), 92.9% (52/56), 82.1% (46/56), and 75.0% (42/56) achieved absolute EASI scores < 7, < 5, < 3, and < 1, respectively; mean body surface area (BSA) was reduced from 17.0% to 0.6% (mean BSA improvement=87.8%); mean IGAxBSA was reduced from 52.1 to 0.8 (mean IGAxBSA improvement=90.7%); and mean Dermatology Life Quality Index (DLQI)/Children's DLQI was reduced from 13 to 1.8 (mean DLQI/CDLQI improvement=86%), with 66.0% (33/50) of patients achieving DLQI/CDLQI 0/1. For patients not achieving IGA 0/1, EASI75, EASI90, and EASI100 at weeks 8-20, these responses were subsequently achieved in 60.0% (6/10), 88.9% (8/9), 84.6% (11/13), and 38.1% (8/21) of patients at week 52±6. Dose alterations occurred in 13 patients (12.7%) (escalation: 6.9%, 7/102; reduction: 5.9%, 6/102). Concomitant systemic therapies were used in 1.0% (1/102) of patients. We noted higher statistically significant achievement of endpoints for systemic biologic/JAKi-naïve vs -experienced patients (EASI75; EASI < 7; EASI < 5; DLQI/CDLQI > 4-point improvement). No significant differences in outcomes were identified between dosing regimens. Frequent AEs included: acne (19.6%, 20/102), hypertriglyceridemia (17.6%, 18/102), elevated creatine phosphokinase (13.7%, 14/102), neutropenia (7.8%, 8/102), and transaminitis (7.8%, 8/102). Seven patients (6.8%) discontinued UPA owing to treatment-related AEs, including one case of venous thromboembolism; four patients (3.9%) discontinued UPA due to patient preference, and one patient (1%) discontinued UPA due to lack of efficacy. No serious infections, tuberculosis, major adverse cardiovascular events, gastrointestinal perforation, malignancy, or deaths were observed in 102.5 patient-years of follow-up. Conclusions In contrast to 52-week data from the Measure Up 1/2 and AD Up clinical trials, our results were superior for several outcome parameters (IGA 0/1, EASI90, EASI100, and DLQI 0/1), possibly owing to a patient population with less extensive baseline disease severity. Additionally, we noted similar achievement of these endpoints versus comparable long-term real-world studies. Safety was consistent with existing data, highlighting acne as a common AE (5.3%-20.3% versus 19.6%). Study limitations include its sample size and retrospective nature. [ABSTRACT FROM AUTHOR]

Introduction Currently approved dosing regimens of upadacitinib (UPA) for moderate-to-severe atopic dermatitis (AD) are 15 mg (UPA15) once daily (QD) and 30 mg (UPA30) QD based on clinical trial data. However, dose alterations may be required in the context of inadequate efficacy, adverse events (AEs), and patient preference. Objectives Our multicenter retrospective study evaluated the effect of upadacitinib dose alterations on real-world effectiveness and safety outcomes in patients with AD at three practices in Canada. Methods Among 119 patients with AD initiated on UPA with > 23-week follow-up, we identified patients undergoing dose alteration (escalation or reduction). Reasons for dose alteration were collected along with effects of dose alteration on effectiveness outcomes including Investigator Global Assessment (IGA), mean Eczema Area and Severity Index (EASI), body surface area (BSA), Dermatology Life Quality Index (DLQI)/Children's DLQI (CDLQI), and IGAxBSA. Impact of dose alteration on incidence and outcomes of AEs was additionally analyzed. Results From 119 total patients with AD initiated on UPA (> 23-week follow-up), 26.9% (32/119) underwent dose alteration: 40.6% (13/32) with dose escalation and 59.4% (19/32) with dose reduction. The mean age of patients who underwent dose alteration was 44.8 (range: 12-79) years; 62.5% (20/32) were female and 15.6% (5/32) were adolescents. Initial doses were UPA15 (43.8%, 14/32) and UPA30 (56.3%, 18/32). The mean time from UPA initiation to dose alteration was 228.3 (range: 9-520) days. Thirteen patients underwent dose escalation: 69.2% (9/13) from UPA15 QD to UPA30 QD and 30.8% (4/13) from UPA30 QD to 45 mg (UPA45) QD. At the time of dose escalation: mean EASI score was 2.8 (mean EASI improvement from baseline: 57.4%), with 53.8% (7/13) and 7.7% (1/13) having achieved 75% and 90% improvements in baseline EASI scores (EASI75 and EASI90), respectively, while IGA scores were 1 (n=5) and 2 (n=8). At follow-up (mean duration: 83.3 days) after dose escalation: mean EASI score was 1.6 (mean EASI improvement: 84.4% [from baseline] and 54% [from date of dose escalation]), with 69.2% (9/13), 61.5% (8/13), 38.5% (5/13), and 61.5% (8/13) of patients achieving EASI75, EASI90, 100% improvement in EASI (EASI100), and IGA 0/1, respectively. Two patients (15.4%) discontinued UPA due to lack of efficacy despite dose escalation. Only 2 AEs were noted with dose escalation: transaminitis (n=1) and elevated creatine phosphokinase (n=1); the patient with transaminitis subsequently discontinued UPA. Nineteen patients underwent dose reduction: UPA30 QD to UPA15 QD (63.1%, 12/19), UPA30 QD to UPA30 every other day (QOD) (10.5%, 2/19), and UPA15 QD to UPA15 QOD (26.3%, 7/19). Reasons for dose reduction included AEs (57.9%, 11/19) and patient preference following clearance or near-clearance (42.1%, 8/19). EASI/IGA responses were maintained in 78.9% (15/19) patients. Following dose reduction, 21.1% (4/19) of patients flared and required re-escalation (mean duration: 147.3 days). AEs requiring dose reduction included acne (36.4%, 4/11), herpes simplex (18.2%, 2/11), transaminitis (18.2%, 2/11), folliculitis (9.1%, 1/11), and recurrent respiratory tract infections (18.2%, 2/11). AEs improved in 54.5% (6/11) patients with dose reduction (mean follow-up: 164.1 days). Conclusions Our real-world data suggests dose escalation from UPA15 to UPA30 and UPA30 to UPA45 (off-label) can result in higher skin clearance without any short-term safety concerns. Comparable to a Japanese real-world study (n=23), we noted incremental benefits with dose escalation, including comparable and superior achievement of EASI75 (69.2% vs. 66.7%) and EASI90 (61.5% vs. 38.1%), respectively. Furthermore, we identified AEs at higher UPA doses can improve through dose reduction with majority of patients (78.9%) maintaining initial effectiveness response. Study limitations include its small sample size and retrospective nature. [ABSTRACT FROM AUTHOR]