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1.
J Cutan Med Surg ; : 12034754241260023, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847375

RESUMO

There has been a call to action to enhance representation of non-white individuals in dermatology clinical trials. Investigations in differential response to treatment across populations are limited, particularly in conditions of commonality, impact, distinct presentation, and diagnosis in non-white participants, such as atopic dermatitis and psoriasis. This systematic review summarized and identified if biologic treatment outcomes in moderate-to-severe atopic dermatitis and psoriasis varied in skin of colour (SOC) participants in phase 3 trials. MEDLINE, COCHRANE, and EMBASE databases were used to conduct the search following PROSPERO registration. Following screening of 3209 articles, 11 studies were collected with 1781 SOC participants with a mean age of 40.99 ± 6.3 years (range: 30.6-51.6 years). Male participants accounted for 76.9% (n = 1370/1781) of the sample, and Chinese, Japanese, Taiwanese, and Korean participants accounted for 64.3%, 24.2%, 4.5%, and 3.4% of participants, respectively. Participants with atopic dermatitis were treated with dupilumab (n = 216/388) and participants with psoriasis were treated with adalimumab (n = 313/1393), bimekizumab (n = 62/1393), ixekizumab (n = 13/1393), secukinumab (n = 117/1393), and ustekinumab (n = 289/1393). No significant SOC population-based outcomes were found across treatment groups. However, differences in baseline characteristics or comorbidities were found, suggesting race or ethnic background should be considered when treatment is prescribed in psoriasis or atopic dermatitis. Although no significant SOC participant differential response to treatment were found, large-scale randomized controlled trials investigating comparable treatment outcomes and stratifying results by SOC population in atopic dermatitis and psoriasis are warranted to confirm these findings.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38860729

RESUMO

BACKGROUND: Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. OBJECTIVES: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. METHODS: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. CONCLUSION: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.

5.
J Allergy Clin Immunol Glob ; 3(3): 100275, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38826624

RESUMO

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting from the complex interplay of genetic and environmental factors, meriting exploration using temporally dynamic biomarkers. DNA methylation-based algorithms have been trained to accurately estimate biological age, and deviation of predicted age from true age (epigenetic age acceleration) has been implicated in several inflammatory diseases, including asthma. Objective: We sought to determine the role of epigenetic and biological aging, telomere length, and epigenetically inferred abundance of 7 inflammatory biomarkers in AD. Methods: We performed DNA methylation-based analyses in a pediatric AD cohort (n = 24, mean ± standard deviation [SD] age 2.56 ± 0.28 years) and age-matched healthy subjects (n = 24, age 2.09 [0.15] years) derived from blood using 5 validated algorithms that assess epigenetic age (Horvath, Skin&Blood) and biological age (PhenoAge, GrimAge), telomere length (TelomereLength), and inflammatory biomarker levels. Results: Epigenetic and biological age, but not telomere length, were accelerated in AD patients for 4 algorithms: Horvath (+0.88 years; 95% confidence interval [CI], 0.33 to 1.4; P = 2.3 × 10-3), Skin&Blood (+0.95 years; 95% CI, 0.67 to 1.2; P = 1.8 × 10-8), PhenoAge (+8.2 years; 95% CI, 3.4 to 13.0; P = 1.3 × 10-3), and GrimAge (+1.8 years 95% CI, 0.22 to 3.3; P = .026). Moreover, patients had increased levels of ß2 microglobulin (+47,584.4 ng/mL; P = .029), plasminogen activation inhibitor 1 (+3,432.9 ng/mL; P = 1.1 × 10-5), and cystatin C (+31,691 ng/mL; P = 4.0 × 10-5), while levels of tissue inhibitor metalloproteinase 1 (-370.7 ng/mL; P = 7.5 × 10-4) were decreased compared to healthy subjects. Conclusion: DNA methylation changes associated with epigenetic and biological aging, and inflammatory proteins appear early in life in pediatric AD and may be relevant clinical biomarkers of pathophysiology.

6.
Arch Dermatol Res ; 316(5): 195, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775978

RESUMO

Chronic arsenic exposure is a global health hazard significantly associated with the development of deleterious cutaneous changes and increased keratinocyte cancer risk. Although arsenic exposure is associated with broad-scale cellular and molecular changes, gaps exist in understanding how these changes impact the skin and facilitate malignant transformation. Recently developed epigenetic "clocks" can accurately predict chronological, biological and mitotic age, as well as telomere length, on the basis of tissue DNA methylation state. Deviations of predicted from expected age (epigenetic age dysregulation) have been associated with numerous complex diseases, increased all-cause mortality and higher cancer risk. We investigated the ability of these algorithms to detect molecular changes associated with chronic arsenic exposure in the context of associated skin lesions. To accomplish this, we utilized a multi-algorithmic approach incorporating seven "clocks" (Horvath, Skin&Blood, PhenoAge, PCPhenoAge, GrimAge, DNAmTL and epiTOC2) to analyze peripheral blood of pediatric and adult cohorts of arsenic-exposed (n = 84) and arsenic-naïve (n = 33) individuals, among whom n = 18 were affected by skin lesions. Arsenic-exposed adults with skin lesions exhibited accelerated epigenetic (Skin&Blood: + 7.0 years [95% CI 3.7; 10.2], q = 6.8 × 10-4), biological (PhenoAge: + 5.8 years [95% CI 0.7; 11.0], q = 7.4 × 10-2, p = 2.8 × 10-2) and mitotic age (epiTOC2: + 19.7 annual cell divisions [95% CI 1.8; 37.7], q = 7.4 × 10-2, p = 3.2 × 10-2) compared to healthy arsenic-naïve individuals; and accelerated epigenetic age (Skin&Blood: + 2.8 years [95% CI 0.2; 5.3], q = 2.4 × 10-1, p = 3.4 × 10-2) compared to lesion-free arsenic-exposed individuals. Moreover, lesion-free exposed adults exhibited accelerated Skin&Blood age (+ 4.2 [95% CI 1.3; 7.1], q = 3.8 × 10-2) compared to their arsenic-naïve counterparts. Compared to the pediatric group, arsenic-exposed adults exhibited accelerated epigenetic (+ 3.1 to 4.4 years (95% CI 1.2; 6.4], q = 2.4 × 10-4-3.1 × 10-3), biological (+ 7.4 to 7.8 years [95% CI 3.0; 12.1] q = 1.6 × 10-3-2.8 × 10-3) and mitotic age (+ 50.0 annual cell divisions [95% CI 15.6; 84.5], q = 7.8 × 10-3), as well as shortened telomere length (- 0.23 kilobases [95% CI - 0.13; - 0.33], q = 2.4 × 10-4), across all seven algorithms. We demonstrate that lifetime arsenic exposure and presence of arsenic-associated skin lesions are associated with accelerated epigenetic, biological and mitotic age, and shortened telomere length, reflecting altered immune signaling and genomic regulation. Our findings highlight the usefulness of DNA methylation-based algorithms in identifying deleterious molecular changes associated with chronic exposure to the heavy metal, serving as potential prognosticators of arsenic-induced cutaneous malignancy.


Assuntos
Arsênio , Metilação de DNA , Epigênese Genética , Encurtamento do Telômero , Humanos , Adulto , Arsênio/efeitos adversos , Arsênio/toxicidade , Feminino , Metilação de DNA/efeitos dos fármacos , Encurtamento do Telômero/efeitos dos fármacos , Masculino , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Mitose/efeitos dos fármacos , Mitose/genética , Pele/patologia , Pele/efeitos dos fármacos , Dermatopatias/induzido quimicamente , Dermatopatias/genética , Dermatopatias/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologia
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