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Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real-life clinical practice. Ninety patients with plaque psoriasis recruited from-Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI ≤1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI ≤1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI ≤1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to -0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real-world practice conditions.
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Anticorpos Monoclonais Humanizados , Psoríase , Humanos , Psoríase/tratamento farmacológico , Psoríase/genética , Feminino , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento , Genótipo , Idoso , Polimorfismo GenéticoRESUMO
BACKGROUND: Combinations of topical (TT) and biological therapies (BT) are a common thing in the routine clinical practice. However, the scientific medical literature on how TT is, actually, used after the initiation of BT is scarce, particularly in combination with anti-IL17, or anti-IL23. OBJECTIVES: To describe the frequency of the concomitant use of TT + BT at baseline and after a 6-month course of several drugs (anti-IL17, ustekinumab, and anti-IL23). Our secondary endpoints are to describe the type of topical therapy used, compare the frequency of use of TT among the different groups of BT, describe the survival of topical therapy in these patients, and identify the factors that can impact the use or discontinuation of topical therapy in these patients (clinical response, quality of life, type of drug, etc.). MATERIALS AND METHODS: This was a retrospective, observational, and single-center study of patients with moderate-to-severe psoriasis treated with anti-IL17 (secukinumab, ixekizumab), anti-IL17R (brodalumab), ustekinumab, and guselkumab from January 2015 through December 2020. RESULTS: We included a total of 138 patients. When treatment started, 82.7% were on TT (55% daily), and after 6 months, 86.6% had discontinued TT. Regarding the analysis by type of drug, at 6 months, we found that 100% of the patients with BRO had discontinued topical treatment. We did not find any significant differences in the frequency of use of TT based on the BT used during the 6-month course of treatment. The estimated mean course of TT was 4.3 months (SD, 6.7). Also, the estimated mean course of TT was significantly shorter in the group of patients who achieved PASI100 (2.8 months vs. 8.1 months). CONCLUSIONS: In our cohort, we saw a significant decrease in the frequency of use of TT at 6 months after starting BT in the routine clinical practice. This reduction occurred earlier in patients who improved their objective clinical response and quality of life.
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Interleucina-17 , Interleucina-23 , Psoríase , Índice de Gravidade de Doença , Humanos , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Masculino , Interleucina-23/antagonistas & inibidores , Feminino , Interleucina-17/antagonistas & inibidores , Pessoa de Meia-Idade , Ustekinumab/uso terapêutico , Ustekinumab/administração & dosagem , Adulto , Quimioterapia Combinada , Qualidade de Vida , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Administração Tópica , Fármacos Dermatológicos/uso terapêutico , Fármacos Dermatológicos/administração & dosagemRESUMO
BACKGROUND: Combinations of topical (TT) and biological therapies (BT) are a common thing in the routine clinical practice. However, the scientific medical literature on how TT is, actually, used after the initiation of BT is scarce, particularly in combination with anti-IL17, or anti-IL23. OBJECTIVES: To describe the frequency of the concomitant use of TT + BT at baseline and after a 6-month course of several drugs (anti-IL17, ustekinumab, and anti-IL23). Our secondary endpoints are to describe the type of topical therapy used, compare the frequency of use of TT among the different groups of BT, describe the survival of topical therapy in these patients, and identify the factors that can impact the use or discontinuation of topical therapy in these patients (clinical response, quality of life, type of drug, etc.). MATERIALS AND METHODS: This was a retrospective, observational, and single-center study of patients with moderate-to-severe psoriasis treated with anti-IL17 (secukinumab, ixekizumab), anti-IL17R (brodalumab), ustekinumab, and guselkumab from January 2015 through December 2020. RESULTS: We included a total of 138 patients. When treatment started, 82.7% were on TT (55% daily), and after 6 months, 86.6% had discontinued TT. Regarding the analysis by type of drug, at 6 months, we found that 100% of the patients with BRO had discontinued topical treatment. We did not find any significant differences in the frequency of use of TT based on the BT used during the 6-month course of treatment. The estimated mean course of TT was 4.3 months (SD, 6.7). Also, the estimated mean course of TT was significantly shorter in the group of patients who achieved PASI100 (2.8 months vs. 8.1 months). CONCLUSIONS: In our cohort, we saw a significant decrease in the frequency of use of TT at 6 months after starting BT in the routine clinical practice. This reduction occurred earlier in patients who improved their objective clinical response and quality of life.
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Interleucina-17 , Interleucina-23 , Psoríase , Índice de Gravidade de Doença , Humanos , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Interleucina-23/antagonistas & inibidores , Masculino , Interleucina-17/antagonistas & inibidores , Feminino , Pessoa de Meia-Idade , Ustekinumab/uso terapêutico , Ustekinumab/administração & dosagem , Quimioterapia Combinada , Adulto , Administração Tópica , Qualidade de Vida , Fármacos Dermatológicos/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVE: The treatment of psoriasis should not only focus on skin affectations but also weigh the parameters for health-related quality of life (HRQoL), thereby tackling the concept of cumulative life course impairment (CLCI) and treating the patient from a holistic perspective. The CRYSTAL study aimed to characterize psoriasis with real-word data from Spanish clinical practice in patients with moderate to severe disease who received continuous systemic treatment for at least 24 weeks by using the absolute Psoriasis Area and Severity Index (PASI) score and its correlation to HRQoL. MATERIAL AND METHODS: This was a non-interventional, cross-sectional study conducted in 30 centers in Spain, with 301 patients between the ages of 18 and 75 years. The study collected data regarding current treatment and absolute PASI and their relationship to HRQoL using the Dermatology Life Quality Index (DLQI), to activity impairment using the Work Productivity and Activity Impairment (WPAI) questionnaire, and to treatment satisfaction. RESULTS: The mean (SD) age was 50.5 (12.5) years, with a duration of disease of 14 (14.1) years. The mean (SD) absolute PASI reported was 2.3 (3.5), with 28.7% of patients presenting with PASI from >1 to ≤3 and 22.6% with PASI>3. Higher PASI scores were associated with higher DLQI (p<0.001) and WPAI scores and lower levels of treatment satisfaction (p<0.001). CONCLUSIONS: These data indicate that achieving lower absolute PASI values may correlate not only with better HRQoL but also with better work productivity and treatment satisfaction.
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Psoríase , Qualidade de Vida , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Espanha/epidemiologia , Estudos Transversais , Psoríase/complicações , Psoríase/tratamento farmacológico , Pele , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: The treatment of psoriasis should not only focus on skin affectations but also weigh the parameters for health-related quality of life (HRQoL), thereby tackling the concept of cumulative life course impairment (CLCI) and treating the patient from a holistic perspective. The CRYSTAL study aimed to characterize psoriasis with real-word data from Spanish clinical practice in patients with moderate to severe disease who received continuous systemic treatment for at least 24 weeks by using the absolute Psoriasis Area and Severity Index (PASI) score and its correlation to HRQoL. MATERIAL AND METHODS: This was a non-interventional, cross-sectional study conducted in 30 centers in Spain, with 301 patients between the ages of 18 and 75 years. The study collected data regarding current treatment and absolute PASI and their relationship to HRQoL using the Dermatology Life Quality Index (DLQI), to activity impairment using the Work Productivity and Activity Impairment (WPAI) questionnaire, and to treatment satisfaction. RESULTS: The mean (SD) age was 50.5 (12.5) years, with a duration of disease of 14 (14.1) years. The mean (SD) absolute PASI reported was 2.3 (3.5), with 28.7% of patients presenting with PASI from >1 to ≤3 and 22.6% with PASI>3. Higher PASI scores were associated with higher DLQI (p<0.001) and WPAI scores and lower levels of treatment satisfaction (p<0.001). CONCLUSIONS: These data indicate that achieving lower absolute PASI values may correlate not only with better HRQoL but also with better work productivity and treatment satisfaction.
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Psoríase , Qualidade de Vida , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Espanha/epidemiologia , Estudos Transversais , Psoríase/complicações , Psoríase/tratamento farmacológico , Pele , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Guselkumab is a monoclonal antibody that blocks the IL-23 pathway with proven efficacy and tolerability in the treatment of moderate-to-severe plaque psoriasis. OBJECTIVES: To assess the persistence, effectiveness and safety of guselkumab in patients with moderate-to-severe psoriasis in real clinical practice in Spain. METHODS: SPRING was a Phase IV, retrospective and non-interventional study analysing patients with moderate-to-severe plaque psoriasis who had initiated guselkumab under clinical practice conditions at least 12 months before inclusion in the study. The primary endpoint was persistence (non-persistence: discontinuation or interruption ≥90 days). Effectiveness was assessed using the Psoriasis Area Severity Index (PASI) and Investigator Global Assessment (IGA). Dermatology Life Quality Index (DLQI) and safety were also evaluated. RESULTS: A total of 284 patients were included between September 2020 and June 2021. The 1-year probability of persistence was 89.6% (86.1%-93.3%). The 1-year probability of persistence was also calculated according to prior biologic treatment, being 90.3% for biologic-naïve patients and 89.5% for patients who received one or more biologic therapies before guselkumab. Additionally, patients were also classified based on the frequency of the administration of guselkumab treatment; the 1-year probability of persistence was 91.9% in patients receiving guselkumab according to the Summary of Product Characteristics and 89.3% in patients with lengthened intervals of administration. After 1 year, PASI 90 was achieved by 56.4% of patients, IGA 0/1 response and BSA <3% were achieved by 65.5% and 77.8% of patients, respectively, and 65.8% achieved a minimal clinically significant difference (>4-point reduction) in the DLQI score at 1 year. Twenty-six adverse reactions (4 of them serious) were reported in 16 patients. CONCLUSIONS: This study suggests that guselkumab has high persistence in real clinical practice in Spain, independently of the previous biologic treatments and changes in the frequency of treatment. Effectiveness and safety are consistent with previously published data.
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BACKGROUND: Limited data are available on long-term efficacy and safety of biologics in patients with psoriasis and metabolic syndrome (MetS), a common comorbidity. OBJECTIVES: This analysis updates tildrakizumab efficacy and safety for up to 5 years in patients with and without MetS. METHODS: This was a post hoc analysis of the double-blind, randomized, placebo-controlled, phase 3 reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) trials in adult patients with moderate to severe chronic plaque psoriasis. Analyses included data through Week 244 from patients who continuously received tildrakizumab 100 (TIL100) or 200 mg (TIL200) and entered the extension studies, stratified by baseline MetS status. Efficacy was assessed via Psoriasis Area and Severity Index (PASI) scores. Safety was evaluated from exposure-adjusted incidence rates (EAIRs) of treatment-emergent adverse events (TEAEs). RESULTS: reSURFACE 1 and reSURFACE 2 analyses included 26 and 44 TIL100-treated patients with MetS, 98 and 167 TIL100-treated patients without MetS, 34 and 30 TIL200-treated patients with MetS, and 111 and 130 TIL200-treated patients without MetS, respectively. There were no clinically relevant differences in PASI 75/90/100 response rates at Week 244 between patients with vs without MetS. The proportion of patients with vs without MetS achieving absolute PASI score <3 at Week 244 was 53.8% vs 69.4% and 77.3% vs 80.8% in reSURFACE 1 and 2, respectively, for TIL100-treated patients and 58.8% vs 72.1% and 63.3% vs 72.3%, respectively, for TIL200-treated patients. In both studies, median reduction from baseline PASI score at all time points in patients with vs without MetS was >83% vs >89% for TIL100 and >85% vs >90% for TIL200. Pooled EAIRs of TEAEs, serious TEAEs, and TEAEs of special interest were similar in patients with and without MetS. CONCLUSIONS: Tildrakizumab maintains efficacy and a favorable safety profile over 5 years in patients with psoriasis regardless of MetS status.
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Anticorpos Monoclonais Humanizados , Síndrome Metabólica , Psoríase , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/tratamento farmacológico , Psoríase/complicações , Psoríase/tratamento farmacológico , Resultado do TratamentoRESUMO
Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.
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Produtos Biológicos , Psoríase , Adolescente , Produtos Biológicos/uso terapêutico , Criança , Humanos , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Psoríase/epidemiologia , Sistema de RegistrosRESUMO
INTRODUCTION: Psoriatic disease is associated with considerable impairment of quality of life (QoL). The PROSE study (NCT02752776) investigated the impact of secukinumab treatment on patient-reported outcomes (PRO) in patients with moderate to severe psoriasis stratified by their treatment history. METHODS: PROSE was a prospective, non-randomised, multicentre study. Patients were categorized at baseline according to treatment history as naïve [naïve to any systemic therapy (N = 663)], conventional systemic [previously exposed to ≥1 conventional systemic (CS) therapy (N = 673)] and biologics [previously exposed to ≥1 biologic therapy (N = 324)]. QoL PROs, efficacy and safety of secukinumab 300 mg were assessed for a period of 52 weeks. RESULTS: The primary objective was met with 70.8% patients achieving a Dermatology Life Quality Index (DLQI) 0/1 response at Week 16 (naÏve, 74.7%; CS, 71.3%; biologic, 61.7%), with effects sustained up to Week 52. Mean Family DLQI (FDLQI) score decreased from 11.5 at baseline (naÏve, 11.3; CS, 11.4; biologic, 12.1) to 2.5 at Week 16 (naÏve, 2.5; CS, 2.3; biologic: 3.5). Substantial improvements in EuroQoL 5-Dimension Health Questionnaire, Numeric Rating Scale for pain, itching and scaling, Health Assessment Questionnaire-Disability Index, Treatment Satisfaction Questionnaire for Medication, and Patient Benefit Index were also observed at Week 16. The QoL gains were associated with substantial improvements in Psoriasis Area and Severity Index and Investigator Global Assessment mod 2011 0/1 response. No meaningful difference was observed in the efficacy or QoL improvements across patient subpopulations. All QoL and efficacy parameter improvements were sustained up to Week 52. Secukinumab treatment was well-tolerated, and no new safety signals were observed. CONCLUSION: Secukinumab treatment resulted in complete normalization of QoL in a substantial proportion of psoriasis patients, and their families, regardless of their prior treatment history.
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Psoríase , Qualidade de Vida , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Humanos , Estudos Prospectivos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
INTRODUCTION: Psoriatic disease is associated with considerable impairment of Quality of Life (QoL). The PROSE study (NCT02752776) examined the impact of secukinumab on patient-reported outcomes in patients with moderate-to-severe psoriasis (PsO) stratified by previous exposure to systemic treatment. METHODS: In this prospective, non-randomized, multicentre study, patients were categorized at baseline according to previous exposure to systemic treatment: naïve [naïve to any systemic treatment (N = 663)], conventional systemic [previously exposed to ≥1 conventional systemic therapy (N = 673)] and biologics [previously exposed to ≥1 biologic (N = 324)]. Baseline demographics including age, gender, race, body weight and body mass index, disease characteristics and patient-reported QoL outcomes [Dermatology Life Quality Index (DLQI), Family DLQI (F-DLQI)] of patients enrolled in the study are reported here. RESULTS: Baseline demographic characteristics were well balanced across the three subpopulations. Naïve patients had a shorter time since diagnosis (15.5 ± 12.1 years) compared with the conventional systemic (19.1 ± 12.5 years) and biologic patients (23.0 ± 12.5 years), and lower rates of psoriatic arthritis (6.6% vs. 17.4% and 27.8%, respectively). Metabolic syndrome (37.6-43.5%), obesity (16.9-19.1%), hyperlipidaemia (15.3-21.9%) and diabetes mellitus (6.8-14.2%) were reported at numerically higher rate in the biologic group. The mean PASI (19.7 ± 7.9), affected Body Surface Area (28.2 ± 15.3%) as well as the Investigator Global Assessment score (patients with score 4: 33.7%) indicated severe disease at baseline and were comparable for the three groups. QoL impairment was evident from mean DLQI (14.1 ± 7.1: naïve = 13.5 ± 6.8; conventional systemic = 14.3 ± 7.0; biologic = 14.8 ± 7.7) and mean F-DLQI (11.5 ± 7.0: naïve = 11.3 ± 7.1; conventional systemic = 11.4 ± 6.7; biologic = 12.1 ± 7.7) also indicated derangement of QoL of patients and their families. CONCLUSION: Patients naïve to systemic treatment had shorter disease journey compared with patients previously exposed to systemic treatments; despite this, the severe impact of disease on patient and family QoL outcomes can be as apparent in naïve patients as in systemically treated patients at baseline.
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Artrite Psoriásica , Psoríase , Superfície Corporal , Humanos , Estudos Prospectivos , Psoríase/tratamento farmacológico , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Treatment persistence is becoming a useful measure to evaluate long-term effectiveness and safety of biological therapies in real-world settings. OBJECTIVE: The main objective of this study was to explore the scientific opinion of a panel of dermatologists and hospital pharmacists to reach a consensus about the impact, causes, and best strategies and interventions that might be associated with improved drug persistence in patients with psoriasis in Spain. METHODS: This research was conducted using a modified Delphi method organized in two rounds and involving a panel of 90 dermatologists and 34 hospital pharmacists. A questionnaire of 70 items was developed. The items proposed to reach a consensus included topics such as definitions and measures in the treatment of psoriasis, analysis of treatment persistence, factors that may influence treatment persistence, impact of treatment persistence and economic cost of treatment. RESULTS: Dermatologists reached a consensus on 77.1% of the items proposed, and hospital pharmacists reached a consensus on 71.4%. Both groups agreed that it is important to use standardized measures in the evaluation of treatment maintenance over time. Dermatologists agreed that treatment survival, persistence and retention are synonymous, but hospital pharmacists considered only treatment persistence as a valid term. In addition, panelists agreed that drug persistence is an indicator of success in the treatment of psoriasis that may be influenced by a drug's effectiveness and safety profile, as well as by patient satisfaction. They agreed that the different causes of treatment discontinuation should be considered in Kaplan-Meier analysis of treatment persistence. Moreover, treatment persistence was agreed to decrease the cost of therapy. CONCLUSION: This Delphi consensus highlights the different perspectives of dermatologists and hospital pharmacists regarding the interpretation of treatment persistence, and the challenge of harmonizing the results obtained.
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Produtos Biológicos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Dermatologistas , Adesão à Medicação , Farmacêuticos , Psoríase/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/economia , Consenso , Técnica Delphi , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/economia , Humanos , Estimativa de Kaplan-Meier , Satisfação do Paciente , Psoríase/economia , Índice de Gravidade de Doença , Espanha , Terminologia como Assunto , Resultado do TratamentoRESUMO
Anti-tumor necrosis factor (anti-TNF) drugs are effective against psoriasis, although 20-30% of patients are nonresponders. Few pharmacogenomic studies have been performed to predict the response to anti-TNF drugs in psoriasis. We studied 173 polymorphisms to establish an association with the response to anti-TNF drugs in patients with moderate-to-severe plaque psoriasis (N=144). We evaluated the response using PASI75 at 3, 6 and 12 months. The results of the multivariate analysis showed an association between polymorphisms in PGLYR4, ZNF816A, CTNNA2, IL12B, MAP3K1 and HLA-C genes and the response at 3 months. Besides, the results for polymorphisms in IL12B and MAP3K1 were replicated at 6 months. We also obtained significant results for IL12B polymorphism at 1 year. Moreover, polymorphisms in FCGR2A, HTR2A and CDKAL1 were significant at 6 months. This is the first study to show an association with these polymorphisms. However, these biomarkers should be validated in large-scale studies before implementation in clinical practice.
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Fármacos Dermatológicos/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Psoríase/tratamento farmacológico , Psoríase/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Biomarcadores/metabolismo , Feminino , Genótipo , Humanos , Masculino , Farmacogenética/métodos , Psoríase/metabolismoRESUMO
Polymorphisms at genes encoding proteins involved in the pathogenesis of psoriasis (Psor) or in the mechanism of action of biological drugs could influence the treatment response. Because the interleukin (IL)-17 family has a central role in the pathogenesis of Psor, we hypothesized that IL17RA variants could influence the response to anti-TNF drugs among Psor patients. To address this issue we performed a cross-sectional study of Psor patients who received the biological treatments for the first time, with a follow-up of at least 6 months. All of the patients were Caucasian, older than 18 years old, with chronic plaque Psor, and had completed at least 24 weeks of anti-TNF therapy (adalimumab, etanercept or infliximab). The treatment response to anti-TNF agents was evaluated according to the achievement of PASI50 and PASI75 at weeks 12 and 24. Those who achieved PASI75 at week 24 were considered good responders. All patients were genotyped for the selected single-nucleotide polymorphisms (SNPs) at IL17RA gene. A total of 238 patients were included (57% male, mean age 46 years). One hundred and five patients received adalimumab, 91 patients etanercept and 42 infliximab. The rs4819554 promoter SNP allele A was significantly more common among responders at weeks 12 (P=0.01) and 24 (P=0.04). We found a higher frequency of AA versus AG+GG among responders, but the difference was only significant at week 12 (P=0.03, odd ratio=1.86, 95% confidence of interval=1.05-3.27). Thus, in the study population, the SNP rs4819554 in the promoter region of IL17RA significantly influences the response to anti-TNF drugs at week 12.
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Polimorfismo de Nucleotídeo Único/genética , Psoríase/genética , Receptores de Interleucina-17/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Alelos , Estudos Transversais , Etanercepte/uso terapêutico , Feminino , Genótipo , Humanos , Infliximab/uso terapêutico , Interleucina-17/genética , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológicoRESUMO
BACKGROUND: The association between hidradenitis suppurativa (HS) and some diseases is becoming relevant in recent years. Providing appropriate management of HS from an early stage requires to include prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat HS potentially related to the onset of a comorbidity. OBJECTIVE: To provide the dermatologist with an accurate, easily used tool that will inform the diagnosis of HS comorbidity, and to facilitate decision-making regarding the referral and treatment of patient with HS-associated comorbidity. METHODS: These recommendations have been developed by a working group composed of seven experts (three dermatologists, a cardiovascular specialist internist, a rheumatologist expert in spondyloarthritis, a gastroenterologist and a psychiatrist) and a team of three methodologist researchers. The expert group selected the HS comorbidities considered in these recommendations through a literature review. The recommendations on diagnostic criteria are based on the relevant clinical practice guidelines for each of the comorbidities and on the recommendations of the experts. The information regarding the repercussion of HS medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. RESULTS: The comorbidities considered in this guide are as follows: cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), inflammatory bowel disease, inflammatory joint disorders and psychological disorders (anxiety and depression). In addition, the association between HS and the consumption of alcohol and tobacco is included. The tables and figures are a precise, easy-to-use tool to systematize the diagnosis of comorbidity in patients with HS and facilitate the decision-making process regarding referral and treatment of patients with an associated disease. CONCLUSION: The application of these recommendations will facilitate the dermatologist practice and benefit HS patients' health and quality of life.
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Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Hidradenite Supurativa/tratamento farmacológico , Hidradenite Supurativa/epidemiologia , Hipertensão/epidemiologia , Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Comorbidade , Técnicas de Apoio para a Decisão , Depressão/diagnóstico , Depressão/epidemiologia , Diabetes Mellitus/diagnóstico , Dislipidemias/diagnóstico , Humanos , Hipertensão/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Síndrome Metabólica/diagnóstico , Obesidade/diagnóstico , Prevalência , Encaminhamento e Consulta , Fumar/epidemiologiaRESUMO
BACKGROUND: The association between psoriasis and some diseases has become relevant in recent years. Providing appropriate management of psoriasis from an early stage requires prompt diagnosis and treatment of concomitant diseases and to prevent any potential comorbidity. This approach should consider the adverse events of the drugs used to treat psoriasis potentially related to the onset of comorbidities. OBJECTIVE: To provide the dermatologist with an accurate and friendly tool for systematizing the diagnosis of psoriasis-associated comorbidities, which generally escapes the scope of the dermatology setting, and to facilitate decision-making about the referral and treatment of patients with comorbidities. METHODS: These position statement recommendations were developed by a working group composed of ten experts (four dermatologists, one cardiologist, one rheumatologist, one gastroenterologist, one nephrologist, one endocrinologist and one psychiatrist) and two health services researchers. The expert group selected the psoriasis comorbidities considered according to their relevance in the dermatology setting. The recommendations on diagnostic criteria are based on the current clinical practice guidelines for each of the comorbidities. The information regarding the repercussion of psoriasis medical treatments on associated comorbid diseases was obtained from the summary of product characteristics of each drug. RESULTS: Recommendations were developed to detect and refer the following psoriasis comorbidities: psoriatic arthritis, cardiovascular risk factors (diabetes, dyslipidaemia, obesity, hypertension and metabolic syndrome), non-alcoholic fatty liver disease, inflammatory bowel disease, kidney disease and psychological disorders (anxiety and depression). In addition, alcohol consumption and tobacco consumption were included. The tables and figures are precise, easy-to-use tools to systematize the diagnosis of comorbidities in patients with psoriasis and facilitate the decision-making process regarding referral and treatment of patients with an associated disease. CONCLUSION: The application of these position statement recommendations will facilitate the dermatologist practice, and benefit psoriasis patients' health and quality of life.
Assuntos
Nefropatias/epidemiologia , Psoríase/epidemiologia , Ansiedade/epidemiologia , Ansiedade/terapia , Comorbidade , Depressão/epidemiologia , Depressão/terapia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Humanos , Hipertensão/epidemiologia , Hipertensão/terapia , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Nefropatias/terapia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/terapia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/epidemiologia , Obesidade/terapia , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: The presence of cutaneous nodules in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs) receiving depot somatostatin analogs (SSAs) is a diagnostic challenge as differential diagnosis between injection site reactions and metastases is essential. OBJECTIVE: To characterize the clinical, radiological, cytological and histopathological features of subcutaneous nodules in patients with GEP-NETs treated with SSAs. MATERIALS AND METHODS: Retrospective, cross-sectional study of patients with GEP-NETs treated with SSAs in whom subcutaneous nodules were detected on routine abdominal computed tomography (CT) scans. High resolution and colour Doppler ultrasonography was performed. Those patients with inconclusive radiological studies went through fine-needle aspiration cytology (FNAC) and/or biopsy. RESULTS: Twelve patients (five males, seven females) were included (six midgut carcinoid NETs, six pancreatic NETs). Three patients received intramuscular depot octreotide, seven subcutaneous lanreotide, and two both treatments. CT scan findings were nonspecific. Sonography revealed a hyperechoic pattern in recent injections, and a hypoechoic pattern with a characteristic hyperechoic peripheral rim in long-term injections (more than 3 months after injection). On colour Doppler sonography, nodules showed no signs of intralesional vascularity. Fine-needle aspiration cytology (FNAC) was performed in five patients, revealing a characteristic acellular proteinaceous material. Biopsy in four patients showed different reactional infiltrates around the acellular material. CONCLUSIONS: High resolution and colour Doppler ultrasonography may be very useful for the differential diagnosis of subcutaneous nodules in patients with GEP-NETs treated with SSAs. FNAC and a biopsy are useful tests for confirmation of the diagnosis in patients with inconclusive findings. We propose a management algorithm.
Assuntos
Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/patologia , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia , Octreotida/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Peptídeos Cíclicos/administração & dosagem , Neoplasias Cutâneas/secundário , Somatostatina/análogos & derivados , Somatostatina/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Adulto , Idoso , Biópsia por Agulha , Estudos Transversais , Preparações de Ação Retardada , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Exame Físico , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico por imagem , Somatostatina/administração & dosagem , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/patologia , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia Doppler em Cores/métodosRESUMO
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is an inducible enzyme that suppresses the immune response. The role of IDO as a negative regulator of inflammatory responses has been documented in several experimental autoimmune diseases. OBJECTIVES: To explore the regulation of IDO by immune cells in psoriasis and its relation with disease severity. METHODS: The expression and activity of IDO were assessed by reverse-transcriptase polymerase chain reaction, flow cytometry and high-performance liquid chromatography in peripheral blood of patients with moderate-to-severe plaque-type psoriasis. The ability of immune cells to express IDO in response to inflammatory stimuli was studied. The functional role of IDO expression was evaluated in a regulatory T cell (Treg) differentiation assay, using cocultures of immature monocyte-derived dendritic cells with autologous peripheral CD4+ T cells. RESULTS: Analysis of the kynurenine-to-tryptophan ratio in serum samples indicated higher IDO activity in patients with psoriasis than in healthy controls. However, correlation studies showed lower IDO activity in those patients with higher Psoriasis Area and Severity Index (PASI). Although myeloid dendritic cells from patients with psoriasis expressed higher levels of IDO than those from healthy controls, these cells did not upregulate IDO in response to a combination of tumour necrosis factor-α, interleukin (IL)-1ß and IL-6 cytokines. The defective expression of IDO correlated with PASI. Immature monocyte-derived dendritic cells from patients with psoriasis also expressed low levels of IDO and induced CD4+ Treg differentiation poorly. CONCLUSIONS: Immune cells from patients with psoriasis have a defect in upregulating IDO in response to inflammation associated with the severity of psoriasis.
Assuntos
Citocinas/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Psoríase/enzimologia , Linfócitos T Reguladores/fisiologia , Estudos de Casos e Controles , Diferenciação Celular/imunologia , Células Dendríticas/fisiologia , Combinação de Medicamentos , Humanos , Leucócitos Mononucleares , Lipopolissacarídeos/farmacologia , Psoríase/imunologia , Linfócitos T Reguladores/citologiaRESUMO
Although the majority of patients with psoriasis vulgaris are treated exclusively with topical therapies, research to develop more effective topical therapies that are associated with higher patient satisfaction has lagged behind the development of systemic agents. The aim of this literature review was to determine whether there is documented evidence that applying an innovative approach to improving the formulation of active ingredients commonly used in the topical treatment of psoriasis can have a positive effect on clinical outcomes and patient-reported outcomes (PROs). The Embase and PubMed databases were searched for articles published between 2001 and 2016 that made direct head-to-head comparisons of different formulations of an active pharmaceutical ingredient (API), focusing on clinical outcomes and PROs. In total, 22 publications on APIs or API combinations met the eligibility criteria (19 head-to-head clinical trials, one pooled analysis, one health-economic modelling study and one systematic review). Significant clinical benefit associated with the use of a reformulated API over an older formulation was reported in three trials of clobetasol propionate, one trial of calcipotriol, three trials of betamethasone and five trials/pooled analyses of calcipotriol/calcipotriene + betamethasone dipropionate (Cal/BD) formulations. Significantly improved PROs associated with the use of a reformulated API over an older formulation were reported in three trials of clobetasol propionate, one trial of betamethasone valerate and two trials of Cal/BD formulations. These results demonstrate that the innovative reformulation of APIs used in the treatment of psoriasis can produce therapies that attain significantly improved clinical outcomes and PROs. This suggests that improvement in topical therapy for psoriasis need not only to be achieved by the identification of new targets and the development of new APIs, but that improvement in the vehicle used to deliver existing APIs has the potential to result in significant clinical and patient benefits.