RESUMO
Objective: Treatment options with disease-modifying antirheumatic drugs (DMARDs) for psoriatic arthritis (PsA) have evolved over recent years. In addition to Janus kinase inhibitors (JAKi), four classes of biologic DMARDs (bDMARDs; interleukin [IL]-23 inhibitors [IL-23i], IL-12/23 inhibitors [IL-12/23i], tumor necrosis factor inhibitors [TNFi], and IL-17 inhibitors [IL-17i]) are currently approved for moderate to severe PsA treatment. There is minimal evidence of the persistence of these drugs among PsA outpatients in a real-world scenario during the period following the approval of JAKi. Therefore, we aimed to analyze the drug survival rates of biologic and JAKi therapies among German PsA outpatients during routine clinical care. Methods: We retrospectively analyzed PsA patients with a new prescription for a biologic or JAKi in the RHADAR database between January 2015 and October 2023. Kaplan-Meier Curves and Cox regression modelling were used to compare drug survival rates. Results: 1352 new prescriptions with bDMARDs (IL-12/23i [n=50], IL-23i [n=31], TNFi [n=774], IL-17i [n=360]) or JAKi (n=137) were identified. The 5-year drug survival rate was 67.8% for IL-17i, 62.3% for TNFi, 53.3% for JAKi, and 46.0% for IL-12/23i. Discontinuation probabilities for JAKi and IL-12/23i were significantly higher compared with TNFi (JAKi hazard ratio [HR] 1.66, [95% CI 1.23-2.24], p=0.001; IL-12/23i HR 1.54, [95% CI 1.02-2.33], p=0.042) and IL-17i (JAKi HR 1.77, [95% CI 1.27-2.47], p=0.001; IL-12/23i HR 1.64, [95% CI 1.06-2.55], p=0.027). JAKi-treated patients had more severe disease and more osteoarthritis (OA) compared to TNFi and more OA compared to IL-17i. Conclusion: German PsA outpatients might persist longer with TNFi and IL-17i compared with IL-12/23i or JAKi. For TNFi, differences in subgroup characteristics and comorbidities (OA) may have affected drug survival rates. For IL-17i, the longer drug survival might not only be related to less OA compared to JAKi and, therefore, might be affected by other factors.
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Antirreumáticos , Artrite Psoriásica , Interleucina-12 , Interleucina-17 , Interleucina-23 , Inibidores de Janus Quinases , Humanos , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Interleucina-17/antagonistas & inibidores , Alemanha , Interleucina-12/antagonistas & inibidores , Interleucina-23/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , Antirreumáticos/uso terapêutico , Adulto , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Idoso , Bases de Dados Factuais , Pacientes Ambulatoriais , Resultado do TratamentoRESUMO
BACKGROUND: Little is known about mortality trends among patients with psoriasis (PsO) and psoriatic arthritis (PsA) in the United States. OBJECTIVES: To ascertain mortality trends of PsO and PsA between 2010 and 2021, focusing on the effects of the COVID-19 pandemic. METHODS: We collected data from the National Vital Statistic System and calculated age-standardized mortality rates (ASMR) and cause-specific mortality for PsO/PsA. We evaluated observed versus predicted mortality for 2020-2021 based on trends from 2010 to 2019 with joinpoint and prediction modelling analysis. RESULTS: Among 5810 and 2150 PsO- and PsA-related deaths between 2010 and 2021, ASMR for PsO dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 2.07% vs. 15.26%; p < 0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (0.27 vs. 0.22) and 2021 (0.31 vs. 0.23). The excess mortality of PsO was 22.7% and 34.8% higher than that in the general population in 2020 (16.4%, 95% CI: 14.9%-17.9%) and 2021 (19.8%, 95% CI: 18.0%-21.6%) respectively. Notably, the ASMR rise for PsO was most pronounced in the female (APC: 26.86% vs. 12.19% in males) and the middle-aged group (APC: 17.67% vs. 12.47% in the old-age group). ASMR, APC and excess mortality for PsA were similar to PsO. SARS-CoV-2 infection contributed to more than 60% of the excess mortality for PsO and PsA. CONCLUSIONS: Individuals living with PsO and PsA were disproportionately affected during the COVID-19 pandemic. Both ASMRs increased at an alarming rate, with the most pronounced disparities among the female and middle-aged groups.
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Artrite Psoriásica , COVID-19 , Psoríase , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artrite Psoriásica/mortalidade , COVID-19/epidemiologia , Pandemias , Psoríase/mortalidade , SARS-CoV-2 , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: This study aimed to assess the mortality of PsA before and during the COVID-19 pandemic. METHODS: From the prospective, multicenter PsART-ID (Psoriatic Arthritis Registry-International Database), patients from Turkey were analyzed by linking the registry to the Turkish Cause of Death Registry. The outcome of interest was death from any cause, pre-pandemic (since the onset of registry-March 2014-March 2020), and during the pandemic (March 2020-May 2021). The crude mortality rate and standardized mortality ratio (SMR) were determined. RESULTS: There were 1216 PsA patients with a follow-up of 7500 patient-years. Overall, 46 deaths (26 males) were observed. In the pre-pandemic period, SMR for PsA vs the general population was 0.95 (0.61-1.49), being higher in males [1.56 (0.92-2.63)] than females [0.62 (0.33-1.17)]. The crude mortality rate in PsA doubled during the pandemic (pre-pandemic crude mortality rate: 5.07 vs 10.76 during the pandemic) with a higher increase in females (2.9 vs 8.72) than males (9.07 vs 14.73). CONCLUSION: The mortality in PsA was found similar to the general population in the pre-pandemic era. The mortality rates in PsA doubled during the pandemic. Whether PsA patients have more risk of mortality than the general population due to COVID-19 needs further studies. Key Points ⢠Decrease in mortality in PsA might be expected with the more effective treatment options and better disease control. ⢠A crude mortality rate is comparable to the general population and not increased until the pandemic. ⢠Currently, there is a 2-fold increase in crude mortality rate possibly due to the COVID-19.
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Artrite Psoriásica , COVID-19 , Feminino , Humanos , Masculino , Artrite Psoriásica/mortalidade , COVID-19/epidemiologia , Pandemias , Estudos Prospectivos , Sistema de Registros , Turquia/epidemiologiaRESUMO
OBJECTIVE: To determine the incidence of psoriatic arthritis (PsA) in a US population and describe trends in incidence and mortality over 5 decades. METHODS: The previously identified population-based cohort that included Olmsted County, Minnesota residents ≥18 years of age who fulfilled PsA criteria during 1970-1999 was extended to include patients with incident PsA during 2000-2017. Age- and sex-specific incidence rates and point prevalence, adjusted to the 2010 US White population, were reported. RESULTS: There were 164 incident cases of PsA in 2000-2017 (mean ± SD age 46.4 ± 12.0 years; 47% female). The overall age- and sex-adjusted annual incidence of PsA per 100,000 population was 8.5 (95% confidence interval [95% CI] 7.2-9.8) and was higher in men (9.3 [95% CI 7.4-11.3]) than women (7.7 [95% CI 5.9-9.4]) in 2000-2017. Overall incidence was highest in the 40-59 years age group. The incidence rate was relatively stable during 2000-2017, with no evidence of an overall increase or an increase in men only (but a modest increase of 3% per year in women), compared to 1970-1999 when a 4%-per-year increase in incidence was observed. Point prevalence was 181.8 per 100,000 population (95% CI 156.5-207.1) in 2015. The percentage of women among those with PsA increased from 39% in 1970-1999 and 41% in 2000-2009 to 54% in 2010-2017 (P = 0.08). Overall survival in PsA did not differ from the general population (standardized mortality ratio 0.85 [95% CI 0.61-1.15]). CONCLUSION: The incidence of PsA in this predominantly White US population was stable in 2000-2017, in contrast to previous years. However, an increasing proportion of women with PsA was found in this study.
Assuntos
Artrite Psoriásica/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artrite Psoriásica/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Prevalência , Fatores Sexuais , Taxa de Sobrevida , Adulto JovemRESUMO
OBJECTIVES: It has been hypothesized that the presence of chronic pain causes excess mortality. Since chronic pain is prevalent among patients with PsA this potential association should be explored. We aimed to investigate whether higher cumulative pain intensity is associated with an excess mortality risk in patients with PsA. METHODS: A nested case-control study using data from the nationwide DANBIO Register (Danish Database for Biological Therapies in Rheumatology) Register and Danish healthcare registers. Cases were patients who died and corresponding to the date of death, matched on sex, year of birth and calendar period at the time of death with up to five controls. Exposure of interest was mean pain intensity reported during the time followed in routine rheumatology practice. Pain intensity was measured using a visual analogue scale from 0 to 100 and conditional logistic regression was used to calculate odds of mortality per 5 unit increase in pain while adjusting for confounders. RESULTS: The cohort consisted of 8019 patients. A total of 276 cases were identified and matched with 1187 controls. Higher mean pain intensity was associated with increased odds of mortality [odds ratio 1.06 (95% CI 1.02, 1.10)] in the crude model, but there was no association [odds ratio 0.99 (95% CI 0.95, 1.03)] when adjusting for additional confounders. Factors shown to increase the odds of mortality were recent glucocorticoid use, concomitant chronic obstructive pulmonary disease, diabetes mellitus, cancer and cardiovascular disease. CONCLUSION: These results indicate that experienced pain in itself is not associated with premature mortality in patients with PsA. However, recent glucocorticoid use and concurrent comorbidities were.
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Artrite Psoriásica/mortalidade , Dor/mortalidade , Sistema de Registros , Idoso , Idoso de 80 Anos ou mais , Artrite Psoriásica/complicações , Estudos de Casos e Controles , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologiaRESUMO
BACKGROUND: There is limited information about mortality rates among patients with psoriasis and psoriatic arthritis (PsA) in North America and their change over the past 2 decades. OBJECTIVE: To compare all-cause and cause-specific mortality rates in patients with psoriasis to the general population in Ontario, Canada, from 1996 to 2016. METHODS: We conducted a population-based, retrospective cohort study of adult residents using administrative health data. All-cause and cause-specific standardized mortality rates, standardized mortality ratios, and excess mortality rates were calculated. RESULTS: 176,858 (2,524 deaths) patients with psoriasis and 15,430 (221 deaths) patients with PsA were identified in 2016. Patients with psoriasis and PsA had standardized excess mortality rates of 1.44 and 2.43 per 1000 population, respectively. Standardized mortality rates decreased by approximately 30% over the study period in both disease groups but remained significantly elevated compared to the general population. The leading causes of death in psoriasis and PsA patients were cancer, circulatory disease, and respiratory conditions. LIMITATIONS: We were unable to classify patients according to disease severity. CONCLUSIONS: Despite improvements in psoriasis treatment, the relative excess mortality, which may be related to risk factors for psoriatic disease, remained unchanged, with an average of approximately 1 to 2 extra deaths per 1,000 patients in 2016.
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Artrite Psoriásica/mortalidade , Causas de Morte/tendências , Psoríase/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Psoriásica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Psoríase/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND/OBJECTIVES: Mortality studies in psoriatic arthritis (PsA) have provided inconsistent results. This study aimed to: 1) Estimate trends in mortality rates among PsA patients over calendar time; 2) Evaluate cause-specific mortality rates in patients with PsA compared to the general population; 3) Identify predictors for mortality in PsA. METHODS: The study was carried out at the University of Toronto Psoriatic Arthritis Clinic where patients are followed prospectively according to a standard protocol at 6- to 12- month intervals. Standardized mortality ratios (SMRs) were calculated overall, by age, and by sex with reference to the Ontario population. Causes of death were recorded by ICD9 and ICD10 codes and cause-specific SMRs were computed. Cox regression models were used to identify predictors for mortality among PsA patients. RESULTS: Among 1490 patients followed over 15062.8 patient-years, 225 (15%) confirmed deaths were recorded (111 females, 114 males). The overall SMR was 0.92 (95% CI: 0.81-1.05), the sex-specific SMRs were 1.08 (95% CI: 0.89-1.30) for females and 0.81 (95% CI: 0.66-0.97) for males. The age-specific SMRs were 3.36 (95% CI: 1.61-6.18), 0.97 (95% CI: 0.68-1.34), 0.88 (95% CI: 0.73-1.06) and 0.86 (95% CI: 0.66-1.11) for 20-39, 40-59, 60-79 and above 80 years of age, respectively. Major causes of death included malignant neoplasms (n=61; SMR=0.97, 95% CI: 0.72-1.28), acute myocardial infarction (n=32; SMR=1.11, 95% CI: 0.74-1.58), and pneumonia (n=14; SMR=2.46, 95% CI: 1.27-4.31). Factors found to be associated with increased mortality include elevated acute phase reactants, presence of comorbidities such as heart disease and cancer, and lower education level. CONCLUSION: Young patients with PsA are at increased mortality risk. Better control of comorbidities may reduce this risk.
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Artrite Psoriásica/mortalidade , Causas de Morte , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
Abstract Background: Psoriatic Arthritis is the spondyloarthritis associated with psoriasis, which is often related to high mortality due to cardiovascular causes. Objectives: To quantify cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity and smoking) and to measure risk by the Global Cardiovascular Risk Score in patients with psoriatic arthritis. Methods: Patients with psoriatic arthritis according to the Classification Criteria for Psoriatic Arthritis, aged between 30 and 74 years and without any other clinically manifest chronic inflammatory disease, atherosclerotic disease or heart failure were included. After an interview, clinical examination and data extraction from medical records, risk stratification was performed using a calculator available on the online platform of the Framingham Heart Study. We considered p < 0.05 as significant. Chi-square test and Fisher's exact test were used to compare frequencies, as well as correlation measurements. Results: 45 patients were included, 68,9% of which were women and the mean age was 53,94 years. Dyslipidemia was confirmed in approximately 93%, hypertension in 46%, obesity in 40%, 33.3% were diabetics and, 13.3%, smokers; 95% had increased abdominal circumference. It was observed that 53% had high cardiovascular risk, 29% had intermediate risk and 18% had low risk. Individuals with altered C-reactive protein and erythrocyte sedimentation rate presented, respectively, higher levels of LDL-C and total cholesterol. Conclusions: There was a high occurrence of risk factors and the majority of the sample was stratified into high or intermediate cardiovascular risk.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Artrite Psoriásica/complicações , Medição de Risco , Fatores de Risco de Doenças Cardíacas , Tabagismo , Artrite Psoriásica/mortalidade , Estudos Transversais , Diabetes Mellitus , Dislipidemias , Hipertensão , ObesidadeRESUMO
Methotrexate (MTX) is recognized as the anchor drug in the algorithm treating chronic arthritis (RA, psoriatic arthritis), as well as a steroid sparing agent in other inflammatory conditions (polymyalgia rheumatica, vasculitis, scleroderma). Its main mechanism of action has been related to the increase in extracellular adenosine, which leads to the effects of A2A receptor in M1 macrophages that dampens TNFα and IL12 production and increases IL1Ra and TNFRp75. By acting on A2B receptor on M2 macrophages it enhances IL10 synthesis and inhibits NF-kB signaling. MTX has also been shown to exert JAK inhibition of JAK2 and JAK1 when tested in Drosophila melanogaster as a model of kinase activity and in human cell lines (nodular sclerosis Hodgkin's lymphoma and acute myeloid leukemia cell lines). These effects may explain why MTX leads to clinical effects similar to anti-TNFα biologics in monotherapy, but is less effective when compared to anti-IL6R in monotherapy, which acting upstream exerts major effects downstream on the JAK1-STAT3 pathway. The MTX effects on JAK1/JAK2 inhibition also allows to understand why the combination of MTX with Leflunomide, or JAK1/JAK3 inhibitor leads to better clinical outcomes than monotherapy, while the combination with JAK1/JAK2 or JAK1 specific inhibitors does not seem to exert additive clinical benefit.
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Artrite Psoriásica/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Leflunomida/uso terapêutico , Metotrexato/uso terapêutico , Animais , Artrite Psoriásica/imunologia , Artrite Psoriásica/mortalidade , Quimioterapia Combinada , Humanos , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 1/imunologia , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/imunologia , Febre Reumática/imunologia , Febre Reumática/patologia , Fator de Transcrição STAT3/imunologiaRESUMO
Objective: To review long-term certolizumab pegol (CZP) safety across all approved indications: rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn's disease (CD). Methods: Data were pooled across 49 UCB-sponsored CZP clinical trials (27 RA, one axSpA, one PsA, five PSO, 15 CD) to August 2017. Serious adverse events (SAEs) of interest (infections, malignancies, autoimmunity/hypersensitivity events, major adverse cardiovascular events (MACE), gastrointestinal (GI) perforations, psoriasis events, laboratory abnormalities) and deaths were medically reviewed by an external expert committee, using predefined case rules. Incidence rates (IRs)/100 patient-years (PY) are presented by indication; standardised mortality and malignancy rates were calculated using WHO/GLOBOCAN/SEER databases. Pregnancies with maternal CZP exposure are also reported. Results: Of 11 317 CZP-treated patients across indications (21 695 PY CZP exposure; maximum: 7.8 years), infections were the most common SAEs (overall IR: 3.62/100 PY; IRs ranged from 1.50/100 PY(PSO) to 5.97/100 PY(CD)). The IR for malignancies was 0.82/100 PY, including lymphoma (0.06/100 PY). MACE and GI perforation IRs in CZP-treated patients were 0.47/100 PY and 0.08/100 PY and were highest in RA and CD, respectively. Patients with PSO had the lowest SAE rates. The incidence of deaths and malignancies aligned with expected general population data. Conclusion: This extensive overview of the CZP safety profile in clinical trials, across all indications, provides large-scale confirmation of previous reports. No new safety signals or relevant non-disease-related laboratory abnormalities were identified. The study demonstrated some indication-specific differences in certain SAE rates that may be attributable to the underlying inflammatory disease.
Assuntos
Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Certolizumab Pegol/uso terapêutico , Doença de Crohn/tratamento farmacológico , Imunossupressores/uso terapêutico , Espondilartrite/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/mortalidade , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/mortalidade , Certolizumab Pegol/farmacologia , Ensaios Clínicos como Assunto , Doença de Crohn/epidemiologia , Doença de Crohn/mortalidade , Feminino , Humanos , Imunossupressores/farmacologia , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Espondilartrite/epidemiologia , Espondilartrite/mortalidade , Resultado do Tratamento , Adulto JovemRESUMO
Objective: The aim of this study was to compare the incidence of cancer and all-cause and cause-specific mortality rates among a cohort of patients with severe PsA receiving TNF inhibitor (TNFi) with those of the general UK population. Methods: Cancers and deaths were identified from the national cancer and the national death registers in patients with PsA included in the British Society for Rheumatology Biologics Register from start of TNFi until 31 December 2012. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were calculated using published cancer and death rates for the general population. SIRs were calculated for both overall cancer risk and non-melanoma skin cancer. SMRs were calculated for (1) all-cause mortality, (2) death from malignancy and (3) death from circulatory disease. Gender-specific analyses were also performed. Results: Thirty-four cancers and 41 deaths among 709 patients were observed. The risk of malignancy overall was not increased (SIR 0.94; 95% CI: 0.65, 1.34). However, there was a significantly increased incidence of non-melanoma skin cancer (SIR 2.12; 95% CI: 1.19, 3.50). The all-cause mortality rate in our cohort was increased (SMR 1.56; CI: 1.12, 2.11). Death from malignancy was not increased, but death from coronary heart disease was increased (SMR 2.42; 95% CI: 1.11, 4.59). Conclusion: In our cohort of patients with severe PsA, the overall incidence of malignancy was similar to that of the general population, although the incidence of non-melanoma skin cancer was increased. All-cause mortality was significantly increased, in part due to excess of deaths attributed to coronary heart disease.
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Antirreumáticos/efeitos adversos , Artrite Psoriásica/mortalidade , Produtos Biológicos/efeitos adversos , Neoplasias/mortalidade , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Artrite Psoriásica/tratamento farmacológico , Causas de Morte , Doença das Coronárias/induzido quimicamente , Doença das Coronárias/mortalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/induzido quimicamente , Sistema de Registros , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/mortalidade , Reino Unido/epidemiologiaRESUMO
Background: Previous studies showed conflicting results regarding the mortality risk in psoriasis patients with respect to disease severity and presence of psoriatic arthritis. This study aimed to determine the mortality risk in patients with mild and severe psoriasis and patients with psoriatic arthritis (PsA). Methods: A nationwide population-based cohort study was conducted based on data from the Taiwan National Health Insurance Research Database between 2002 and 2012. Incident psoriasis subjects were classified into two groups: psoriasis without arthritis and psoriasis with arthritis. Patients who had received systemic therapy and/or phototherapy were classified as having severe psoriasis; otherwise, patients were classified as having mild psoriasis. Control subjects without psoriasis were selected to match each psoriasis patient from the database within the same observational period. Cox proportional hazards analysis was used to compare the hazard ratio (HR) of time to death. Results: A total of 106,701 patients with psoriasis were included in this study. After controlling for demographics and comorbidities, psoriasis patients had a higher mortality risk compared with the control group (HR 1.41; 95% confidence interval (CI) 1.36 to 1.46). Compared with psoriasis alone, the mortality risk was not increased for PsA (HR = 1.01; 95% CI 0.93 to 1.10). Besides, severe psoriasis did not increase mortality risk compared with mild psoriasis (HR = 1.0; 95% CI 0.95 to 1.06). Conclusions: Patients with psoriasis had a higher mortality risk compared with control subjects, whereas psoriasis severity and presence of PsA had no impact on mortality risk in psoriasis patients.
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Artrite Psoriásica/epidemiologia , Artrite Psoriásica/mortalidade , Psoríase/epidemiologia , Medição de Risco/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taiwan/epidemiologiaRESUMO
OBJECTIVE: To compare the risk of major adverse cardiovascular events (MACE) in a large observational cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or axial spondyloarthritis (SpA) patients. METHODS: We conducted a mixed retrospective and prospective cohort study using data from patients with RA, PsA, or axial SpA included in the Swiss Clinical Quality Management registry. The primary outcome of interest was a composite of myocardial infarction, transient or permanent cerebrovascular event, or cardiovascular-associated death. RESULTS: A total of 5,315 patients were eligible for the analysis of incidence, with a total follow-up time of 37,495 patient-years for RA, 19,837 patient-years for axial SpA, and 9,171 patient-years for PsA. The unadjusted incidence rate of MACE per 1,000 patient-years was 2.67 for RA, 1.41 for axial SpA, and 1.42 for PsA. Compared to the unadjusted incidence rate ratios (IRRs) in patients with RA, those in patients with axial SpA were 0.53 (95% confidence interval [95% CI] 0.34-0.80; P = 0.003) and in patients with PsA were 0.53 (95% CI 0.30-0.95; P = 0.03). After adjustment for traditional cardiovascular risk factors, age at disease onset, sex, and disease duration, the difference was not significant between RA and axial SpA (adjusted IRR 0.93 [95% CI 0.51-1.69]; P = 0.80) or between RA and PsA (adjusted IRR 0.56 [95% CI 0.27-1.14]; P = 0.11). We found a similar result with the analysis of prevalence. CONCLUSION: There was no significant difference in the incidence and prevalence of MACE between RA and axial SpA or PsA, suggesting that inflammation, rather than a particular disease, drives the increased risk of cardiovascular disease.
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Artrite Psoriásica/epidemiologia , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/epidemiologia , Espondilartrite/epidemiologia , Adulto , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/mortalidade , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/mortalidade , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Transtornos Cerebrovasculares/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Prevalência , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Espondilartrite/diagnóstico , Espondilartrite/mortalidade , Suíça/epidemiologia , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Methotrexate (MTX) is widely used as disease modifying treatment for psoriasis and psoriatic arthritis (PsA). Rheumatological and dermatological guidelines to prevent MTX-induced adverse events diverge in the number and frequency of blood tests. These differences are not based on evidence indicating a higher risk for patients with psoriasis compared to PsA or rheumatic arthritis (RA). This raises the question if multiple testing increases safety, or results in false positive signals potentially leading to early withdrawal of an effective treatment. OBJECTIVE: Compare the effects of MTX monitoring strategies by rheumatologists and dermatologists regarding drug survival, reasons for withdrawal and safety. METHODS: Retrospective follow-up of all patients diagnosed with psoriasis by dermatologists or PsA by rheumatologists. Included were consecutive patients who started methotrexate (MTX) between 2006 and 2012 and had a scheduled follow-up by dermatologist or rheumatologist. Exclusions were: drug not started after the first prescription or incomplete availability of lab data. Data were extracted from electronic records: start and stop dates and dosing of MTX; treatment with folic acid and dose; reasons for withdrawal of MTX; numbers of blood sampling and types of laboratory tests performed for MTX safety; number of abnormal tests; occurrence of any serious adverse event (SAE). RESULTS: 190 Psoriasis and 196 PsA patients starting methotrexate (MTX) were included. Age and sex were comparable. PsA patients used higher initial and maximum doses of MTX and folic acid, but psoriasis patients had a higher frequency of abnormal laboratory results (0.14 vs 0.03 per treatment month, p<0.001), resulting in a striking difference in withdrawal of MTX for abnormal liver enzymes (15.8% vs 3.6%, p<0.001). In PsA patients MTX was withdrawn less frequently for ineffectiveness (15.8 vs 24.2%, p<0.05) leading to longer drug survival in the first course of treatment (37.4±30 vs 18.8±19.1 months). Repeated courses of MTX were more often prescribed by rheumatologists than by dermatologists. There were no significant differences in the occurrence of SAE (psoriasis 0.0041 vs PsA 0.0038 per treatment month) or death (1.6% vs 2.0%) between these groups. Hospital admissions related to infection were recorded in 6 (3.1%) PsA vs 4 (2.1%) psoriasis patients. CONCLUSION: Strict monitoring by dermatologists resulted in more abnormal findings, which reduced drug survival of MTX. The limited monitoring strategy by rheumatologists was not associated with more SAEs. Further research in other populations is needed to confirm whether reduced intensity of monitoring can optimize the use of MTX with sufficient long-term safety.
Assuntos
Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/mortalidade , Metotrexato , Adulto , Idoso , Idoso de 80 Anos ou mais , Dermatologistas , Feminino , Seguimentos , Humanos , Masculino , Sistemas Computadorizados de Registros Médicos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Metotrexato/farmacocinética , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , ReumatologistasRESUMO
Golimumab is a recombinant human monoclonal antibody targeted against tumour necrosis factor-alpha (TNF-α). Golimumab is effective in the management of patients with active psoriatic arthritis (PsA). The aim of this study is to evaluate the clinical efficacy and survival of golimumab monotherapy versus co-administration with methotrexate (MTX) in patients with PsA in the clinical practice. This retrospective observational trial included patients with PsA. Efficacy was assessed by disease activity scores - DAS28, BASDAI, physician global assessment of disease (PGA) and CRP. Golimumab survival rate was estimated using the Kaplan-Meier analysis and univariate and multivariate Cox regression models. Forty-one patients with PsA were recruited; 26 patients were treated with golimumab, whereas 15 patients received combination therapy with MTX. The treatment resulted in significantly improved clinical measures of disease activity in comparison with baseline, including DAS28 CRP (4.1 vs 2.6, p ≤ 0.0001) and BASDAI (5.6 vs 3.8, p ≤ 0.001). Overall, 29 (71%) patients continued golimumab treatment (18 patients on monotherapy and 11 on combination therapy). The difference in the duration of golimumab survival between the combination therapy and monotherapy groups was not statistically significant (12.5 vs 12 months, p = 0.2). Similar efficacy profiles and survival rates were documented in patients with PsA regardless of the co-administration of methotrexate.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Psoriásica/tratamento farmacológico , Metotrexato/uso terapêutico , Adulto , Idoso , Artrite Psoriásica/mortalidade , Quimioterapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: Our primary objective was to study the long-term survival on drug (SOD) of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) treated with golimumab (GLM) in real life settings. METHODS: This was a retrospective, observational study of all patients treated with GLM in 4 Academic Centres in Greece during a 4-year period (09/2010-06/2014). SOD was analysed using Kaplan-Meier survival analysis, while Cox regression analysis estimating hazard ratios (HRs) for different baseline variables associated with drug discontinuation was performed for each disease. RESULTS: 328 patients (RA: 166, PsA: 82, AS: 80) were included. The estimated SOD at 2 and 3 years was 68% and 62% overall and was better for AS (79% and 76%) compared to RA (69% and 60%, p=0.067) and PsA (58% and 53%, p=0.001) patients; no difference was noted between RA and PsA patients (p=0.204). There was no difference in SOD between biologic-naïve and experienced nor between non-biologic co-treated or GLM monotherapy treated patients. Seropositivity (rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) was associated with a lower risk for GLM discontinuation by multivariate analysis (HR=0.5, 95% CI=0.0.25-1.1, p=0.05) in RA patients. During 606 patient-years of follow-up, 11 (3.3%) patients discontinued GLM due to adverse events (AE), accounting for 11% of treatment discontinuations. The rates of serious AEs and serious infections were 2.3 and 1.0/100-patient-years, respectively. CONCLUSIONS: In this real-life study, GLM showed a high 3-year SOD in patients with inflammatory arthritides with a low rate of discontinuation due to AEs.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Artrite Psoriásica/mortalidade , Artrite Reumatoide/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Espondilite Anquilosante/mortalidade , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVES: Smoking is associated with an increased risk of psoriatic arthritis (PsA) in the general population, but not among patients with psoriasis. We sought to clarify the possible methodological mechanisms behind this paradox. METHODS: Using 1995-2015 data from The Health Improvement Network, we performed survival analysis to examine the association between smoking and incident PsA in the general population and among patients with psoriasis. We clarified the paradox using mediation analysis and conducted bias sensitivity analyses to evaluate the potential impact of index event bias and quantify its magnitude from uncontrolled/unmeasured confounders. RESULTS: Of 6.65 million subjects without PsA at baseline, 225 213 participants had psoriasis and 7057 developed incident PsA. Smoking was associated with an increased risk of PsA in the general population (HR 1.27; 95% CI 1.19 to 1.36), but with a decreased risk among patients with psoriasis (HR 0.91; 95% CI 0.84 to 0.99). Mediation analysis showed that the effect of smoking on the risk of PsA was mediated almost entirely through its effect on psoriasis. Bias-sensitivity analyses indicated that even when the relation of uncontrolled confounders to either smoking or PsA was modest (both HRs=~1.5), it could reverse the biased effect of smoking among patients with psoriasis (HR=0.9). CONCLUSIONS: In this large cohort representative of the UK general population, smoking was positively associated with PsA risk in the general population, but negatively associated among patients with psoriasis. Conditioning on a causal intermediate variable (psoriasis) may even reverse the association between smoking and PsA, potentially explaining the smoking paradox for the risk of PsA among patients with psoriasis.
Assuntos
Artrite Psoriásica/etiologia , Psoríase/complicações , Fumar/efeitos adversos , Adulto , Artrite Psoriásica/mortalidade , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de Sobrevida , Reino Unido/epidemiologiaRESUMO
Objective: The objective of this study was to examine cause-specific mortality in patients with PsA compared with the general population and compared with patients with RA. Methods: A cohort study was performed using The Health Improvement Network among patients aged 18-89 years with data from 1994 to 2010. PsA and RA were defined by medical codes, and up to 10 unexposed controls were matched on practice and start date within the practice. Cause of death was classified using categories from UK death statistics. Each death was manually reviewed to ensure appropriate classification. Age- and sex-adjusted hazard ratios (HRs) and multivariable adjusted HRs were calculated using competing risks survival regression. Results: Among patients with PsA (8706), RA (41 752) and unexposed controls (81 573), 470, 7004 and 5269 deaths were observed, respectively. The most common causes of death among all patients were cardiovascular disease, followed by malignancy, respiratory deaths and infection. Cause of death was unknown in â¼25%. Among PsA patients, cardiovascular (1.09, 0.91-1.32), respiratory (0.97, 0.79-1.20), malignancy (1.03, 0.86-1.25) and infection deaths (1.05, 0.79-1.39) were not elevated. Among patients with RA, cardiovascular (1.55, 1.44-1.66), respiratory (1.85, 1.72-2.01), malignancy (1.18, 1.08-1.28) and infection deaths (2.21, 2.00-2.44) were significantly elevated compared with population controls. Although less common, suicide deaths were elevated in PsA and RA (HR 3.03 and 2.47, respectively). Conclusion: Overall mortality and cause-specific mortality risk were not elevated among patients with PsA except for suicide deaths. Patients with RA were at increased risk of deaths from cardiovascular, respiratory, cancer and infectious diseases.
Assuntos
Artrite Psoriásica/mortalidade , Artrite Reumatoide/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Psoriásica/complicações , Artrite Reumatoide/complicações , Causas de Morte , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Adulto JovemRESUMO
Psoriatic arthritis occurs commonly in those with psoriasis and is associated with progressive joint destruction, physical disability, reduced quality of life and increased mortality. For many patients the currently available treatment options including the anti-TNF treatments are inadequate. Recent data suggest that ustekinumab can provide an effective treatment option in these patients. We discuss the role of ustekinumab in the treatment of psoriatic arthritis and highlight areas requiring further work.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Qualidade de Vida , Artrite Psoriásica/mortalidade , Artrite Psoriásica/fisiopatologia , Progressão da Doença , Humanos , Psoríase/tratamento farmacológico , Psoríase/patologia , Resultado do Tratamento , UstekinumabRESUMO
BACKGROUND: There are conflicting reports in the literature of the mortality risk among patients with psoriatic arthritis (PsA). The objective of this study was to examine the risk of mortality in patients with PsA compared with matched controls, patients with psoriasis and those with rheumatoid arthritis (RA). METHODS: A longitudinal cohort study was performed in a large UK medical record database, The Health Improvement Network, among patients with PsA, rheumatoid arthritis (RA) or psoriasis with data from 1994 to 2010. Unexposed controls were matched on practice and start date within the practice for each patient with PsA. Cox proportional hazards models were used to calculate the relative hazards for death. RESULTS: Patients with PsA (N=8706), RA (N=41 752), psoriasis (N=138 424) and unexposed controls (N=82 258) were identified; 1 442 357 person-years were observed during which 21 825 deaths occurred. Compared with population controls, patients with PsA did not have an increased risk of mortality after adjusting for age and sex (disease-modifying antirheumatic drug (DMARD) users: HR 0.94, 95% CI 0.80 to 1.10; DMARD non-users: HR 1.06, 95% CI 0.94 to 1.19) whereas patients with RA had increased mortality (DMARD users: HR 1.59, 95% CI 1.52 to 1.66; DMARD non-users: HR 1.54, 95% CI 1.47 to 1.60). Patients with psoriasis who had not been prescribed a DMARD had a small increased risk of mortality (HR 1.08, 95% CI 1.04 to 1.12) while those who had been prescribed a DMARD, indicating severe psoriasis, were at increased risk (HR 1.75, 95% CI 1.56 to 1.95). CONCLUSIONS: Patients with RA and psoriasis have increased mortality compared with the general population but patients with PsA do not have a significantly increased risk of mortality.