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2.
Pediatr Dermatol ; 40(6): 1071-1073, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37740597

RESUMEN

A retrospective chart review of 332 pediatric psoriasis patients seen at a single academic institution from 2012 to 2022 was conducted to examine the risk factors associated with palmoplantar psoriasis (PP), a painful and treatment-resistant subtype of plaque psoriasis affecting hands and feet. Black patients have a 6.386-fold increase in the odds of having PP compared to White patients and males have a 2.241-fold increase in the odds of having PP. Black and Hispanic/Latino patients displayed a higher prevalence of nail and palm/sole involvement (p < .0001), whereas White patients exhibited more scalp involvement (p = .04). This study reveals the importance of considering the diagnosis of PP in Black male patients based on its demographic prevalence, which may in turn impact clinical care for these patients.


Asunto(s)
Negro o Afroamericano , Psoriasis , Niño , Humanos , Masculino , Psoriasis/diagnóstico , Psoriasis/etnología , Estudios Retrospectivos , Población Blanca
3.
Arch Dermatol Res ; 315(8): 2359-2363, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37166524

RESUMEN

Considering the known disparities in racial representation in psoriasis clinical trials, this study sought to characterize travel distance and time to reach a psoriasis clinical trial site as a potential barrier to trial participation for multiple demographic and geographic variables. We determined travel distance and time from every census tract population center in the United States to the nearest psoriasis clinical trial site using ArcGIS and linked travel estimates to demographic characteristics in each census tract based on 2020 American Community Survey. The average distance and time traveled to reach a psoriasis clinical trial site nationally were 45.6 miles and 51.8 min, respectively. Urban residence and Northeast location had significantly lower travel distance and time relative to their geographic counterparts. Travel burden was significantly greater among Native American and Black races, individuals without college education and Veterans Affairs beneficiaries relative to their counterparts. These findings reveal disparate access regarding rurality, race, education and insurance type, which may encourage investigators to increase travel funding for underrepresented groups and diversity recruitment efforts to promote access to psoriasis clinical trials.


Asunto(s)
Ensayos Clínicos como Asunto , Accesibilidad a los Servicios de Salud , Disparidades en Atención de Salud , Psoriasis , Viaje , Humanos , Población Negra/estadística & datos numéricos , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Viaje/estadística & datos numéricos , Estados Unidos/epidemiología , Ensayos Clínicos como Asunto/estadística & datos numéricos , Psoriasis/epidemiología , Psoriasis/etnología , Psoriasis/terapia , Indio Americano o Nativo de Alaska/estadística & datos numéricos , Disparidades en Atención de Salud/etnología , Disparidades en Atención de Salud/estadística & datos numéricos
4.
Exp Dermatol ; 32(8): 1263-1271, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36843152

RESUMEN

Generalized Pustular psoriasis (GPP), a rare and potentially life-threatening auto-inflammatory disease, is associated with IL36RN mutations. Here, we analyse the prevalence of IL36RN mutations in our multi-ethnic GPP cohort and assess differences in the clinical profile of patients with (IL36RN-positive) and without (IL36RN-negative) mutations. IL36RN mutations were present in 17.7% of 137 GPP patients (29.7% of Chinese cases, 17.3% of Malay cases, but 0% of Indian patients). 92% of these individuals carried the c.115 + 6 T > C mutation. Male: female ratio was 1:2.3. Females predominate in both groups with no significant difference between IL36RN-positive and IL36RN-negative individuals. The overall mean age (±SD) at disease onset for GPP was 37.6 ± 17.2 years, but disease onset was significantly earlier in IL36RN-positive vs IL36RN-negative cases (mean age:30.6 ± 18.92 vs. 39.2 ± 16.49 years, p = 0.027). IL36RN-positive patients were less likely to have associated plaque psoriasis (52.4% vs. 83.5%, p-value = 0.002). There was no difference in the common clinical and laboratory manifestations or triggers of GPP between IL36RN-positive and -negative patients, except for geographic tongue which was significantly more common in IL36RN-positive patients (41.7% vs. 11.9%, p-value = 0.002). Annual flare rate was significantly higher in IL36RN-positive compared to IL36RN-negative (mean ± SD of 1.92 ± 1.32 vs. 1.46 ± 0.90, p = 0.041) cases. However, no significant difference in the rate of hospitalization and length of hospital stay was observed between the two groups. These observations demonstrate that IL36RN disease alleles occur with varying frequencies among Asian populations and are associated with a severe, early-onset clinical phenotype.


Asunto(s)
Interleucinas , Psoriasis , Femenino , Humanos , Masculino , Enfermedad Aguda , Pueblo Asiatico , Enfermedad Crónica , Interleucinas/genética , Malasia , Mutación , Psoriasis/epidemiología , Psoriasis/etnología , Psoriasis/genética , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad
6.
Medicine (Baltimore) ; 99(47): e22339, 2020 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-33217788

RESUMEN

More and more researches have been carried out on the association between the tumor necrosis factor-α (TNF-α) 308 G/A polymorphism and psoriasis, however, controversial results have emerged in these studies. This meta-analysis was performed to quantitatively clarify the relationship between TNF-α 308 G/A polymorphism and the risk of psoriasis in different populations. Databases of PubMed, Springer Link, Ovid, Chinese Wanfang Data Bases, Chinese National Knowledge Infrastructure and Chinese Biology Medicine were investigated until June 2019. The association between the TNF-α 308 G/A polymorphism and psoriasis was evaluated by calculating the pooled odds ratio (OR) and 95% confidence intervals (CIs). A total of 26 studies including 3657 patients and 3197 controls were screened out. In the overall population, the pooled results showed a reduced psoriasis risk with the TNF-α 308 G/A polymorphism (A vs G: OR = 0.77, 95% CI = 0.67-0.89; AA+GA vs GG: OR = 0.72, 95% CI = 0.61-0.86). In the subgroup analysis stratified by geographic locations, the TNF-α 308 G/A polymorphism was significantly associated with a reduced risk of psoriasis in Germany (A vs G: OR = 0.67, 95% CI = 0.57-0.78; AA+GA vs GG: OR = 0.62, 95% CI = 0.52-0.75), as well as in China (AA+GA vs GG: OR = 0.71, 95% CI = 0.52-0.98) and Poland (A vs G: OR = 0.61, 95% CI = 0.38-0.97; AA+GA vs GG: OR = 0.59, 95% CI = 0.35-0.99). This study indicated a significantly reduced psoriasis risk associated with the TNF-α 308 G/A polymorphism in Germans, as well as in Chinese and Poles populations compared with other populations. Ethnicity and geographic locations probably play a pivotal role in the genetic association of psoriasis.


Asunto(s)
Polimorfismo de Nucleótido Simple , Psoriasis/genética , Factor de Necrosis Tumoral alfa/genética , Humanos , Psoriasis/etnología , Factores de Riesgo
7.
Eur J Dermatol ; 30(5): 554-560, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-33021475

RESUMEN

BACKGROUND: The efficacy and safety of secukinumab, an interleukin-17 inhibitor, as systemic treatment for patients with moderate-to-severe psoriasis have been demonstrated, but real-world data pertaining to this is limited in China. OBJECTIVE: To evaluate the efficacy and safety of secukinumab in clinical practice in Chinese psoriasis patients with or without psoriatic arthritis (PsA) and identify potential baseline factors that affect the response of patients to secukinumab treatment. MATERIALS & METHODS: Data from 81 patients treated with secukinumab for at least 16 weeks were analysed in a retrospective observational study. RESULTS: After 16 weeks of treatment with secukinumab, 91.1%, 73%, and 38.3% of patients achieved a PASI 75 (75% improvement based on the Psoriasis Area and Severity Index), PASI 90, and PASI 100, respectively. A significant improvement in the quality of life of patients was also observed. Notably, baseline factors, such as young age, lower BMI, no scalp involvement and absence of concomitant PsA, were associated with better clinical response to secukinumab. Approximately 42% of patients (34/81) experienced adverse events, of which the most common was pruritus. CONCLUSION: The results demonstrated that secukinumab appears to be an effective treatment alternative for the majority of Chinese plaque psoriasis patients. Baseline factors, including age, BMI, scalp involvement and concomitant presence of PsA, were associated with response to secukinumab.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Pueblo Asiatico , Fármacos Dermatológicos/uso terapéutico , Psoriasis/tratamiento farmacológico , Psoriasis/etnología , Adulto , Factores de Edad , Edad de Inicio , Anticuerpos Monoclonales Humanizados/efectos adversos , Índice de Masa Corporal , Fármacos Dermatológicos/efectos adversos , Femenino , Humanos , Interleucina-17/antagonistas & inhibidores , Masculino , Persona de Mediana Edad , Prurito/inducido químicamente , Calidad de Vida , Estudios Retrospectivos , Dermatosis del Cuero Cabelludo/tratamiento farmacológico , Índice de Severidad de la Enfermedad
8.
Eur J Dermatol ; 30(5): 580-590, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-33052103

RESUMEN

BACKGROUND: The efficacy and safety of calcipotriol plus betamethasone dipropionate gel for the treatment of scalp psoriasis has previously been demonstrated in a four-week trial in a Chinese population. OBJECTIVE: To evaluate the long-term safety and efficacy of two-compound gel in Chinese adult patients with scalp psoriasis. MATERIALS & METHODS: A multicentre, prospective, randomized, active-controlled trial was established in which subjects were randomized (at a ratio of 4:1) to receive either two-compound gel once daily or calcipotriol scalp solution twice daily for 28 weeks. Incidence of adverse drug reactions (ADRs) of any type and adverse events (AEs) of concern associated with long-term corticosteroid use on the scalp were evaluated. RESULTS: A total of 951 subjects were randomly assigned to receive either two-compound gel (n=760) or calcipotriol scalp solution (n=191). The incidence of ADRs was significantly lower in the two-compound gel group compared with the calcipotriol scalp solution group (11.7 vs. 22.2%, p<0.001). There was no significant difference in treatment-emergent adverse events (TEAEs) associated with long-term topical corticosteroid use on the scalp (1.1% vs. 0%, p=0.369) between the two groups. A statistically significant difference in the percentage of visits with treatment success according to the Subject's Global Assessment was observed (p=0.009); more subjects had visits with 100% treatment success (15.2 vs. 6.3%) and fewer subjects had visits with 0% treatment success (23.7 vs. 30.8%) using two-compound gel compared to calcipotriol scalp solution. CONCLUSION: The two-compound gel was well tolerated and effective in the long-term management of scalp psoriasis in Chinese patients.


Asunto(s)
Antiinflamatorios/uso terapéutico , Betametasona/análogos & derivados , Calcitriol/análogos & derivados , Fármacos Dermatológicos/uso terapéutico , Psoriasis/tratamiento farmacológico , Dermatosis del Cuero Cabelludo/tratamiento farmacológico , Adulto , Anciano , Antiinflamatorios/efectos adversos , Pueblo Asiatico , Betametasona/efectos adversos , Betametasona/uso terapéutico , Calcitriol/efectos adversos , Calcitriol/uso terapéutico , Fármacos Dermatológicos/efectos adversos , Esquema de Medicación , Quimioterapia Combinada , Femenino , Geles , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Psoriasis/etnología , Dermatosis del Cuero Cabelludo/etnología , Soluciones , Resultado del Tratamiento
11.
J Invest Dermatol ; 140(4): 799-805.e1, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31376382

RESUMEN

Most psoriasis-related genes or loci identified by GWAS represent common clusters and are located in noncoding regions of the human genome, providing only limited evidence for the roles of rare coding variants in psoriasis. Two exome-wide case-control genotyping data sets (11,245 cases and 11,177 controls) were obtained from our previous study. Quality controls were established for each data set, and the markers remaining in each set were annotated using ANNOVAR. Gene-based analysis was performed on the annotation results. A total of 250 and 35 genes in the Exome_Fine and Exome_Asian array cohorts, respectively, exceeded the threshold (P < 4.43 × 10-6). Merged gene-based analysis was then conducted on the same set of SNPs from seven genes common to both arrays, and the chi-square test was used to confirm all gene-based results. Ultimately, four susceptibility genes were identified: BBS7 (Pcombine = 1.38 × 10-29), GSTCD (Pcombine = 8.35 × 10-47), LIPK (Pcombine = 1.02 × 10-19), and PPP4R3B (Pcombine = 1.79 × 10-33). This study identified four susceptibility genes for psoriasis via a gene-based method using rare variants, contributing to our understanding of the pathogenesis of psoriasis.


Asunto(s)
Etnicidad , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido Simple , Psoriasis/genética , China/epidemiología , Exoma , Femenino , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Psoriasis/etnología , Psoriasis/metabolismo
12.
Am J Clin Dermatol ; 21(2): 265-274, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31845122

RESUMEN

Current evidence suggests that there are notable differences in the severity of psoriasis between racial and ethnic groups. While the US Latino population is growing rapidly, there is little research on the various factors impacting disease severity in this minority population. This review evaluates the current evidence on psoriasis in Latinos within the US. Psoriasis affects the US Latino population at a lower prevalence, with more severe disease and a greater quality-of-life impact than their White counterparts. In addition, Latinos with psoriasis experience higher rates of comorbidities, such as depression, obesity, and diabetes compared with Whites. There is evidence showing non-inferior or better response to systemic treatments, such as etanercept, secukinumab, and brodalumab, in this population. The combination of barriers to care and lack of involvement in research limit the current understanding of the mechanisms responsible for the pathologic outcomes and the environmental and social disparities observed. Future studies that reflect the growing proportion of minorities in the US may help close these knowledge gaps and improve care.


Asunto(s)
Psoriasis/etnología , Comorbilidad , Costo de Enfermedad , Hispánicos o Latinos , Humanos , Prevalencia , Psoriasis/psicología , Psoriasis/terapia , Calidad de Vida , Estados Unidos/epidemiología
13.
Clin Pharmacokinet ; 59(3): 311-326, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31758502

RESUMEN

Risankizumab is a humanized immunoglobulin (Ig) G1 monoclonal antibody developed and approved for the treatment of moderate-to-severe plaque psoriasis at a dose of 150 mg administered subcutaneously at weeks 0 and 4, and every 12 weeks thereafter. Ongoing trials are investigating the use of risankizumab in other inflammatory autoimmune diseases. Risankizumab exhibits linear pharmacokinetics when administered intravenously (0.01 mg/kg-1200 mg) or subcutaneously (0.25 mg/kg-300 mg), with a long terminal half-life of approximately 28 days. Following subcutaneous administration, peak plasma concentration was reached approximately 3-14 days after dosing, with an estimated bioavailability of 89%. Population pharmacokinetic analyses identified bodyweight, high titers of antidrug antibodies occurring in < 2% of evaluated subjects, baseline serum albumin, baseline high-sensitivity C-reactive protein, and baseline serum creatinine to be statistically correlated with risankizumab clearance, but none of them had a clinically meaningful impact on risankizumab efficacy in psoriasis patients following the clinical dosing regimen. Exposure-response analyses in psoriasis patients demonstrated that the maximum efficacy was achieved with the clinically approved regimen and there was no apparent correlation between risankizumab exposure and safety. A dedicated drug interaction cocktail study in patients with psoriasis demonstrated a lack of therapeutic protein-drug interaction potentials for risankizumab and various cytochrome P450 substrates. In this article, we review the clinical pharmacology data available to date for risankizumab, which supported the clinical development program and ultimately regulatory approvals for risankizumab in the treatment of patients with moderate-to-severe plaque psoriasis.


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacocinética , Anticuerpos Monoclonales/farmacocinética , Inmunoglobulina G/uso terapéutico , Psoriasis/tratamiento farmacológico , Administración Intravenosa , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/sangre , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/sangre , Anticuerpos Monoclonales Humanizados/uso terapéutico , Peso Corporal , Proteína C-Reactiva/análisis , Ensayos Clínicos como Asunto , Creatinina/sangre , Interacciones Farmacológicas , Femenino , Semivida , Humanos , Inmunoglobulina G/administración & dosificación , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Psoriasis/etnología , Psoriasis/inmunología , Seguridad , Albúmina Sérica/análisis , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
14.
Clin Pharmacokinet ; 58(8): 1059-1068, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30915660

RESUMEN

BACKGROUND: Tildrakizumab is an anti-interleukin-23p19 monoclonal antibody recently approved for the treatment of chronic plaque psoriasis. METHODS: This analysis characterizes the population pharmacokinetics of subcutaneous tildrakizumab and identifies covariates influencing exposure in 2098 healthy volunteers and subjects with psoriasis. Tested covariates included body weight, formulation type, sex, age, race, serum albumin, creatinine clearance, Japanese origin, prior treatment with a biologic agent, subject status (subjects with psoriasis vs. healthy volunteers), and ethnicity. RESULTS: The pharmacokinetics was described by a one-compartment model with first-order absorption and elimination kinetics, and inter-individual variability on clearance, volume of distribution, and absorption rate constant. The pharmacokinetics was characterized by low clearance and limited volume of distribution. In subjects with psoriasis, the geometric mean clearance (coefficient of variation) was 0.32 L/day (38%), volume of distribution was 10.8 L (24%), and absorption and elimination half-life were 1.5 days (18%) and 23.4 days (23%), respectively, with an absorption lag time of 1.2 h. For the 100-mg dose, steady-state area under the plasma concentration vs. time curve for one dosing interval and maximum plasma concentration were 305 µg*day/mL (41%) and 8.1 µg/mL (34%), respectively. Steady state was achieved by 16 weeks with the clinical regimen (dosing on week 0 and week 4 and every 12 weeks thereafter) with 1.1-fold accumulation in maximum plasma concentration. Healthy subjects had 31% higher bioavailability than subjects with psoriasis. Subjects with increased body weight had a lower area under the plasma concentration-time curve at steady state vs. those with lower body weight. The modeled exposures were contained within clinical comparability bounds for all covariates including body weight. CONCLUSIONS: The pharmacokinetics of tildrakizumab behaves like a typical monoclonal antibody without requiring dosage adjustment. TRIAL REGISTRATION: NCT01729754, NCT01225731, NCT01722331.


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacocinética , Interleucina-23/antagonistas & inhibidores , Psoriasis/tratamiento farmacológico , Adulto , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Disponibilidad Biológica , Variación Biológica Poblacional , Peso Corporal , Estudios de Casos y Controles , Enfermedad Crónica , Creatinina/análisis , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Psoriasis/etnología , Albúmina Sérica
15.
J Invest Dermatol ; 139(8): 1672-1679.e1, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30738054

RESUMEN

In the United States, black patients are less likely than white patients to receive biologic treatment for their psoriasis. We conducted a qualitative free-listing study to identify patient-generated factors that may explain this apparent racial disparity in psoriasis treatment by comparing the perceptions of biologics and other psoriasis therapies between white and black adults with psoriasis. Participants included 68 white and black adults with moderate to severe psoriasis who had and had not received biologic treatment. Each participant was asked to list words in response to verbal probes querying five psoriasis treatments: self-injectable biologics, infliximab, methotrexate, apremilast, and phototherapy. Salience scores indicating the relative importance of each word were calculated, and salient words were compared across each race/treatment group. Participants who had experience with biologics generally associated positive words with self-injectable biologics. Among biologic-naïve participants, "apprehension," "side effects," and "immune suppression" were most salient. "Unfamiliar" and "dislike needles" were salient only among black participants who were biologic naïve. Participants were generally unfamiliar with the other psoriasis therapies except phototherapy. Unfamiliarity with biologics, particularly among black, biologic-naïve patients, may partly explain the existing racial disparity in biologic treatment for psoriasis and might stem from lack of exposure to or poor understanding of biologics.


Asunto(s)
Productos Biológicos/administración & dosificación , Conocimientos, Actitudes y Práctica en Salud/etnología , Disparidades en Atención de Salud , Fototerapia/psicología , Psoriasis/terapia , Adulto , Anciano , Productos Biológicos/efectos adversos , Femenino , Humanos , Inyecciones/instrumentación , Inyecciones/psicología , Masculino , Persona de Mediana Edad , Agujas , Aceptación de la Atención de Salud/psicología , Fototerapia/efectos adversos , Psoriasis/etnología , Psoriasis/psicología , Investigación Cualitativa , Grupos Raciales/psicología , Autoadministración/psicología , Factores Socioeconómicos , Estados Unidos
16.
PLoS One ; 14(1): e0210076, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30650098

RESUMEN

BACKGROUND: Correlation between severity of psoriasis and psoriatic arthritis (PsA) is inconsistent. Also, human leukocyte antigen (HLA)-Cw6 was found to be underrepresented in severe psoriasis who failed conventional systemic therapies, but the effect of HLA polymorphism on PsA severity needs to be confirmed. OBJECTIVES: To describe the severity of psoriasis, demographic features and HLA polymorphism among Chinese patients with active peripheral type PsA who had inadequate response to conventional disease-modifying antirheumatic drugs. METHODS: We included all patients with PsA who had at least 3 tender and swollen peripheral joints despite at least two conventional non-biologic treatments in our clinic. Demographic results were compared with global pivotal studies of biologics for PsA. HLA-Cw and HLA-DRB1 genotyping was also analyzed. RESULTS: We identified 60 patients who met our inclusion criteria. The male to female ratio was 1.31:1. The majority of patients presented with psoriasis first (81.7%). The mean interval between psoriasis and PsA was 7.2 ± 8.1 years (mean ± SD). The baseline number of tender and swollen joints was 14.9 ± 10.7 and 11.3 ±10.2, respectively. In total, 41.7% subjects had more than 3% body surface area involvement of psoriasis. Genotyping of HLA-Cw and HLA-DRB1 was performed in 47 subjects. HLA-Cw*0702 was the most frequent allele (29.8%), followed by HLA-Cw*01 (26.6%). The frequency of HLA-Cw*0602 allele was similar to normal population. The most frequent HLA-DRB1 allele was HLA-DRB1*04 (20.2%), followed by HLA-DRB1*08 (16.0%). No cases carrying HLA-DRB1*13 were detected. CONCLUSIONS: Compared with Western population, our patients had less psoriasis and PsA burden. The frequencies of HLA-Cw*06, HLA-Cw*12, and HLA-DRB1*07 were not increased. In contrast, HLA-Cw*0702 and HLA-DRB1*08 allele frequencies were increased compared with psoriasis patients and normal population in Taiwan. Future studies are still needed to characterize the demographic and genetic features of high need PsA patients.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Predisposición Genética a la Enfermedad/genética , Antígenos HLA/genética , Polimorfismo Genético , Adulto , Alelos , Artritis Psoriásica/etnología , Artritis Psoriásica/genética , Pueblo Asiatico/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/etnología , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/tratamiento farmacológico , Psoriasis/etnología , Psoriasis/genética , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Taiwán
17.
Clin Pharmacokinet ; 58(3): 375-387, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30123942

RESUMEN

BACKGROUND AND OBJECTIVES: Risankizumab is a humanized anti-interleukin-23 monoclonal antibody in development for the treatment of several inflammatory diseases. This work characterized the pharmacokinetics of risankizumab and evaluated covariates that may affect its exposures using phase I and II trial data in subjects with psoriasis and Crohn's disease. METHODS: Plasma concentration measurements from a phase I study and a phase II study in subjects with psoriasis (n = 157; single doses of 0.01-5 mg/kg intravenously, 0.25-1 mg/kg subcutaneously, and 18 mg subcutaneously, and multiple doses of 90 and 180 mg subcutaneously), and a phase II study in subjects with Crohn's disease (n = 115; doses of 200 or 600 mg intravenously every 4 weeks followed by 180 mg subcutaneously every 8 weeks) were analyzed using non-linear mixed-effects modeling. The model was qualified using bootstrap and simulation-based diagnostics. RESULTS: A two-compartment model with first-order absorption and elimination described the pharmacokinetics of risankizumab. Considering the body weight and baseline albumin central tendency differences between disease populations, risankizumab clearance, steady-state volume of distribution, and terminal-phase elimination half-life were estimated to be approximately 0.35 L/day, 11.7 L, and 27 days, respectively, for a typical 90-kg subject with psoriasis with an albumin level of 42 g/L, and 0.31 L/day, 8.45 L, and 22 days, respectively, for a typical 65-kg subject with Crohn's disease with an albumin level of 37 g/L. Risankizumab absolute subcutaneous bioavailability and absorption rate constant were 72% and 0.18 day-1, respectively. Inter-individual variability for clearance was 37%. CONCLUSIONS: Risankizumab displayed pharmacokinetic characteristics typical for an IgG1 monoclonal antibody with no apparent target-mediated disposition. Accounting for the effects of body weight and baseline albumin explained the small differences in the pharmacokinetics of risankizumab between psoriasis and Crohn's disease, with no further differences between the patient populations.


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacocinética , Anticuerpos Monoclonales/farmacocinética , Enfermedad de Crohn/tratamiento farmacológico , Interleucina-23/antagonistas & inhibidores , Psoriasis/tratamiento farmacológico , Administración Intravenosa , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Disponibilidad Biológica , Variación Biológica Poblacional/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Enfermedad de Crohn/sangre , Enfermedad de Crohn/etnología , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Modelos Biológicos , Psoriasis/sangre , Psoriasis/etnología , Albúmina Sérica/efectos de los fármacos
18.
J Eur Acad Dermatol Venereol ; 33(2): 325-332, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30317671

RESUMEN

BACKGROUND: Erythrodermic and generalized pustular psoriasis are rare, difficult to treat forms of psoriasis. In previous reports, we documented 24- and 52-week findings of an open-label, phase 3 trial (UNCOVER-J) of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis; most patients responded to treatment and maintained response through 52 weeks. OBJECTIVE: To assess the long-term (>3 years) efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis. METHODS: These subgroup analyses were of a partial population of patients from UNCOVER-J (NCT01624233; Sponsored by Eli Lilly and Company), specifically those with erythrodermic psoriasis (N = 8) or generalized pustular psoriasis (N = 5). These patients received 160 mg ixekizumab at Week 0, ixekizumab 80 mg every 2 weeks through Week 12, and ixekizumab 80 mg every 4 weeks thereafter up to Week 244. This regimen is consistent with the regimen approved in Japan for plaque, erythrodermic, and generalized pustular psoriasis and psoriatic arthritis. Efficacy assessments included Global Improvement Score (GIS), Psoriasis Area and Severity Index (PASI), dermal symptoms (for patients with generalized pustular psoriasis), Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS). Safety assessments included treatment-emergent adverse events and adverse events of special interest. RESULTS: Most patients had a GIS of resolved or improved from Week 12 onwards, and all patients had early and sustained improvement in PASI and dermal symptom (generalized pustular psoriasis only) scores. Mean improvements in DLQI and Itch NRS at Week 12 were sustained through Week 244. Ixekizumab was well tolerated over 3 years of treatment in patients with erythrodermic psoriasis or generalized pustular psoriasis, and no new safety concerns were identified. CONCLUSION: These findings suggest that ixekizumab can be an effective long-term treatment option for erythrodermic or generalized pustular psoriasis.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Seguridad del Paciente , Psoriasis/tratamiento farmacológico , Psoriasis/patología , Adulto , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Subcutáneas , Japón , Masculino , Persona de Mediana Edad , Psoriasis/etnología , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento
19.
Acta Derm Venereol ; 99(1): 84-88, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30176044

RESUMEN

Genome-wide association studies have recently identified a number of non-major histocompatibility complex regions associated with psoriatic arthritis. However, data on Chinese patients with psoriatic arthritis and the differences between psoriatic arthritis and cutaneous psoriasis are limited. This study genotyped 12 single nucleotide polymorphisms in 379 patients with psoriatic arthritis, 376 with cutaneous psoriasis, and 760 healthy controls using Sequenom's Mass ARRAY system. The aim of the study was to expand the database for psoriatic arthritis and cutaneous psoriasis, and develop a genetic prediction system for the early diagnosis of psoriatic arthritis in the Chinese population. One variant in NFKBIA, rs12883343, had a significantly different association with psoriatic arthritis than with cutaneous psoriasis (p = 4.93×10-10, odds ratio 2.371). This suggests that there are differences in the pathogenesis of psoriatic arthritis and cutaneous psoriasis.


Asunto(s)
Artritis Psoriásica/genética , Inhibidor NF-kappaB alfa/genética , Polimorfismo de Nucleótido Simple , Psoriasis/genética , Adulto , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/etnología , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Bases de Datos Genéticas , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Psoriasis/diagnóstico , Psoriasis/etnología , Factores de Riesgo
20.
Am J Clin Dermatol ; 20(2): 267-276, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30471012

RESUMEN

BACKGROUND: Data on treatment outcomes in patients with psoriasis who have skin of color are limited. Brodalumab has shown efficacy in patients with moderate-to-severe plaque psoriasis. OBJECTIVE: Our objective was to evaluate the efficacy, safety, and health-related quality of life associated with brodalumab in patients with skin of color participating in two phase III, multicenter, randomized, double-blind, placebo- and active comparator-controlled studies (AMAGINE-2/-3). METHODS: Patients were self-categorized into racial subgroups (black, Asian, or white) or the non-mutually exclusive ethnic subgroup Hispanic/Latino. Patients were randomized to receive brodalumab 210 mg every 2 weeks (Q2W) or ustekinumab (45 mg in patients weighing ≤ 100 kg and 90 mg in patients weighing > 100 kg) for 52 weeks. Skin clearance was monitored using the Psoriasis Area and Severity Index (PASI) and Static Physician's Global Assessment (sPGA). Treatment-emergent adverse events (TEAEs) were summarized by treatment and racial and ethnic subgroup. Health-related quality of life was assessed using the Dermatology Life Quality Index (DLQI). RESULTS: During the 12-week induction phase, 613 patients received ustekinumab (black, n = 20; Asian, n = 24; white, n = 551; Hispanic/Latino, n = 68) and 1236 patients received brodalumab 210 mg Q2W (black, n = 36; Asian, n = 39; white, n = 1116; Hispanic/Latino, n = 132). At week 52, a total of 590 patients received continuous ustekinumab (black, n = 19; Asian, n = 23; white, n = 532; Hispanic/Latino, n = 64) and 339 patients were re-randomized to continue receiving brodalumab 210 mg Q2W (black, n = 10; Asian, n = 7; white, n = 308; Hispanic/Latino, n = 40). Among patients who received brodalumab 210 mg Q2W, skin clearance response rates were similar across racial and ethnic subgroups at week 12 and week 52; rates of 75%, 90%, and 100% improvement in PASI from baseline were also higher, as was sPGA score ≤ 1, than in patients who received ustekinumab across all racial and ethnic subgroups. Rates of TEAEs and ≥ 5-point improvement in DLQI score were similar across racial and ethnic subgroups. CONCLUSIONS: Brodalumab 210 mg Q2W is well tolerated and efficacious across diverse racial and ethnic subgroups in patients with psoriasis, including black, Asian, white, and Hispanic/Latino patients. TRIAL REGISTRY: ClinicalTrials.gov identifier NCT01708603 (AMAGINE-2); NCT01708629 (AMAGINE-3).


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Psoriasis/tratamiento farmacológico , Ustekinumab/administración & dosificación , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Ensayos Clínicos Fase III como Asunto , Fármacos Dermatológicos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/etnología , Psoriasis/patología , Calidad de Vida , Grupos Raciales/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Pigmentación de la Piel , Resultado del Tratamiento , Ustekinumab/efectos adversos
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