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2.
Pediatr Dermatol ; 40(6): 1071-1073, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37740597

RESUMO

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.


Assuntos
Negro ou Afro-Americano , Psoríase , Criança , Humanos , Masculino , Psoríase/diagnóstico , Psoríase/etnologia , Estudos Retrospectivos , População Branca
3.
Arch Dermatol Res ; 315(8): 2359-2363, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37166524

RESUMO

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.


Assuntos
Ensaios Clínicos como Assunto , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Psoríase , Viagem , Humanos , População Negra/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , População Rural/estatística & dados numéricos , Viagem/estatística & dados numéricos , Estados Unidos/epidemiologia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Psoríase/epidemiologia , Psoríase/etnologia , Psoríase/terapia , Indígena Americano ou Nativo do Alasca/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos
4.
Exp Dermatol ; 32(8): 1263-1271, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36843152

RESUMO

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.


Assuntos
Interleucinas , Psoríase , Feminino , Humanos , Masculino , Doença Aguda , Povo Asiático , Doença Crônica , Interleucinas/genética , Malásia , Mutação , Psoríase/epidemiologia , Psoríase/etnologia , Psoríase/genética , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade
6.
Medicine (Baltimore) ; 99(47): e22339, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217788

RESUMO

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.


Assuntos
Polimorfismo de Nucleotídeo Único , Psoríase/genética , Fator de Necrose Tumoral alfa/genética , Humanos , Psoríase/etnologia , Fatores de Risco
7.
Eur J Dermatol ; 30(5): 554-560, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33021475

RESUMO

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.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Povo Asiático , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Psoríase/etnologia , Adulto , Fatores Etários , Idade de Início , Anticorpos Monoclonais Humanizados/efeitos adversos , Índice de Massa Corporal , Fármacos Dermatológicos/efeitos adversos , Feminino , Humanos , Interleucina-17/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Prurido/induzido quimicamente , Qualidade de Vida , Estudos Retrospectivos , Dermatoses do Couro Cabeludo/tratamento farmacológico , Índice de Gravidade de Doença
8.
Eur J Dermatol ; 30(5): 580-590, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33052103

RESUMO

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.


Assuntos
Anti-Inflamatórios/uso terapêutico , Betametasona/análogos & derivados , Calcitriol/análogos & derivados , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Dermatoses do Couro Cabeludo/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/efeitos adversos , Povo Asiático , Betametasona/efeitos adversos , Betametasona/uso terapêutico , Calcitriol/efeitos adversos , Calcitriol/uso terapêutico , Fármacos Dermatológicos/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Géis , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psoríase/etnologia , Dermatoses do Couro Cabeludo/etnologia , Soluções , Resultado do Tratamento
11.
J Invest Dermatol ; 140(4): 799-805.e1, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31376382

RESUMO

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.


Assuntos
Etnicidade , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Psoríase/genética , China/epidemiologia , Exoma , Feminino , Marcadores Genéticos/genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Psoríase/etnologia , Psoríase/metabolismo
12.
Am J Clin Dermatol ; 21(2): 265-274, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31845122

RESUMO

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.


Assuntos
Psoríase/etnologia , Comorbidade , Efeitos Psicossociais da Doença , Hispânico ou Latino , Humanos , Prevalência , Psoríase/psicologia , Psoríase/terapia , Qualidade de Vida , Estados Unidos/epidemiologia
13.
Clin Pharmacokinet ; 59(3): 311-326, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31758502

RESUMO

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.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais/farmacocinética , Imunoglobulina G/uso terapêutico , Psoríase/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Peso Corporal , Proteína C-Reativa/análise , Ensaios Clínicos como Assunto , Creatinina/sangue , Interações Medicamentosas , Feminino , Meia-Vida , Humanos , Imunoglobulina G/administração & dosagem , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Psoríase/etnologia , Psoríase/imunologia , Segurança , Albumina Sérica/análise , Índice de Gravidade de Doença , Resultado do Tratamento
14.
Clin Pharmacokinet ; 58(8): 1059-1068, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30915660

RESUMO

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.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Interleucina-23/antagonistas & inibidores , Psoríase/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Disponibilidade Biológica , Variação Biológica da População , Peso Corporal , Estudos de Casos e Controles , Doença Crônica , Creatinina/análise , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Psoríase/etnologia , Albumina Sérica
15.
J Invest Dermatol ; 139(8): 1672-1679.e1, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30738054

RESUMO

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.


Assuntos
Produtos Biológicos/administração & dosagem , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Disparidades em Assistência à Saúde , Fototerapia/psicologia , Psoríase/terapia , Adulto , Idoso , Produtos Biológicos/efeitos adversos , Feminino , Humanos , Injeções/instrumentação , Injeções/psicologia , Masculino , Pessoa de Meia-Idade , Agulhas , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Fototerapia/efeitos adversos , Psoríase/etnologia , Psoríase/psicologia , Pesquisa Qualitativa , Grupos Raciais/psicologia , Autoadministração/psicologia , Fatores Socioeconômicos , Estados Unidos
16.
PLoS One ; 14(1): e0210076, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30650098

RESUMO

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.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Predisposição Genética para Doença/genética , Antígenos HLA/genética , Polimorfismo Genético , Adulto , Alelos , Artrite Psoriásica/etnologia , Artrite Psoriásica/genética , Povo Asiático/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Psoríase/etnologia , Psoríase/genética , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Taiwan
17.
Clin Pharmacokinet ; 58(3): 375-387, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30123942

RESUMO

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.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais/farmacocinética , Doença de Crohn/tratamento farmacológico , Interleucina-23/antagonistas & inibidores , Psoríase/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Disponibilidade Biológica , Variação Biológica da População/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Doença de Crohn/sangue , Doença de Crohn/etnologia , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Psoríase/sangue , Psoríase/etnologia , Albumina Sérica/efeitos dos fármacos
18.
J Eur Acad Dermatol Venereol ; 33(2): 325-332, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30317671

RESUMO

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.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Segurança do Paciente , Psoríase/tratamento farmacológico , Psoríase/patologia , Adulto , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Japão , Masculino , Pessoa de Meia-Idade , Psoríase/etnologia , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
19.
Acta Derm Venereol ; 99(1): 84-88, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30176044

RESUMO

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.


Assuntos
Artrite Psoriásica/genética , Inibidor de NF-kappaB alfa/genética , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Adulto , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/etnologia , Povo Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Bases de Dados Genéticas , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Psoríase/diagnóstico , Psoríase/etnologia , Fatores de Risco
20.
Am J Clin Dermatol ; 20(2): 267-276, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30471012

RESUMO

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).


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Ustekinumab/administração & dosagem , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Ensaios Clínicos Fase III como Assunto , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/etnologia , Psoríase/patologia , Qualidade de Vida , Grupos Raciais/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Pigmentação da Pele , Resultado do Tratamento , Ustekinumab/efeitos adversos
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