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1.
Drugs Aging ; 39(9): 715-727, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35859228

RESUMO

BACKGROUND: Psoriasis is a common inflammatory disease in any age group, but also in older patients (≥ 65 years of age). Since older patients are often excluded from clinical trials, limited data specifically on this growing population are available, e.g. regarding the safety and performance of biological treatment. AIMS: We aimed to give insight into this specific population by comparing the drug survival and safety of biologics in older patients with that in younger patients. METHODS: In this real-world observational study, data from 3 academic and 15 non-academic centers in The Netherlands were extracted from the prospective BioCAPTURE registry. Biologics included in this study were tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-12/23, and IL-23 inhibitors. Patients were divided into two age groups: ≥ 65 years and < 65 years. The Charlson Comorbidity Index (CCI) was used to measure comorbid disease status, and all adverse events (AEs) that led to treatment discontinuation were classified according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. All AEs that led to treatment discontinuation were studied to check whether they could be classified as serious AEs (SAEs). Kaplan-Meier survival curves for overall 5-year drug survival and split according to reasons of discontinuation (ineffectiveness or AEs) were constructed. Cox regression models were used to correct for possible confounders and to investigate associations with drug survival in both age groups separately. Psoriasis Area and Severity Index (PASI) scores during the first 2 years of treatment and at the time of treatment discontinuation were assessed and compared between age groups. RESULTS: A total of 890 patients were included, of whom 102 (11.4%) were aged ≥ 65 years. Body mass index, sex, and distribution of biologic classes (e.g. TNFα, IL12/23) were not significantly different between the two age groups. A significantly higher CCI score was found in older patients, indicative of more comorbidity (p < 0.001). The 5-year ineffectiveness-related drug survival was lower for older patients (44.5% vs. 60.5%; p = 0.006), and the 5-year overall (≥ 65 years: 32.4% vs. < 65 years: 42.1%; p = 0.144) and AE-related (≥ 65 years: 82.1% vs. < 65 years: 79.5%; p = 0.913) drug survival was comparable between age groups. Of all AEs (n = 155) that led to discontinuation, 16 (10.3%) were reported as SAEs but these only occurred in younger patients. After correcting for confounders, the same trends were observed in the drug survival outcomes. Linear regression analyses on PASI scores showed no statistical differences at 6, 12, 18, and 24 months of treatment between age groups. CONCLUSIONS: This study in a substantial, well-defined, prospective cohort provides further support that the use of biologics in older patients seems well-tolerated and effective. Biologic discontinuation due to AEs did not occur more frequently in older patients. Older patients discontinued biologic treatment more often due to ineffectiveness, although no clear difference in PASI scores was observed. More real-world studies on physician- and patient-related factors in older patients are warranted.


Assuntos
Produtos Biológicos , Psoríase , Idoso , Produtos Biológicos/uso terapêutico , Humanos , Estudos Prospectivos , Psoríase/tratamento farmacológico , Sistema de Registros , Resultado do Tratamento
3.
J Eur Acad Dermatol Venereol ; 32(4): 615-623, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29121430

RESUMO

BACKGROUND: A considerable disease period often precedes initiation of a biologic in patients with psoriasis. Little is known about this important period in patients' lives. Evaluation of this 'journey' can reveal important insights and opportunities for physicians and healthcare decision makers. OBJECTIVES: (i) To describe patient and treatment characteristics until the start of biologic treatment in patients with severe psoriasis, (ii) to assess shifts in early (2005-2009) versus established (2010-2015) biologics prescription periods, (iii) to assess changes in hospital/day care admissions before vs. after starting biologics. METHODS: Explorative, retrospective study on the treatment characteristics of the disease period until first biologic, presented with descriptive statistics of patients included in the BioCAPTURE registry. Journeys of 2005-2009 and 2010-2015 were compared with statistical tests to identify important shifts. RESULTS: Median TUS (time until conventional systemic) was 11.0 years and median TUB (time until biologic) was 18.9 years for all patients treated from 2005 to 2015. Most patients received three different conventional antipsoriatic systemic therapies. We noticed a small trend towards a shorter journey (TUB) with only two conventional systemic agents instead of three before initiating a biologic in later years (2010-2015, vs. 2005-2009). We also noticed a significant decrease in (day care) admissions comparing the two years before, versus the first two years after the start of a biologic treatment (17.7 vs. 8.6 admissions/100 follow-up years, P < 0.001). Cyclosporine, intensive topical treatment (dithranol), retinoids and PUVA therapy lost popularity in recent years. CONCLUSION: The 'journey' of patients with psoriasis towards a biologic is still long and characterized by many different treatments. Shifts towards fewer conventional drugs before biologic initiation and a clear decrease in hospital and day care admissions before vs. after a biologic are seen. Improvement of this journey, especially in young or recently diagnosed patients, can decrease negative influences on patients' lives and reduce societal impact.


Assuntos
Produtos Biológicos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Sistema de Registros , Adulto , Idoso , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Países Baixos , Admissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos
4.
Br J Dermatol ; 176(3): 786-793, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27454758

RESUMO

BACKGROUND: It is important to assess which patients with psoriasis are more likely to achieve high clinical responses on biologics. OBJECTIVES: To assess the number of treatment episodes (TEs) that achieve a 100% improvement in Psoriasis Area and Severity Index (PASI 100), PASI 90 or PASI ≤ 5 at week 24 of biological treatment, and which baseline patient characteristics predict treatment response. METHODS: Data from patients with psoriasis treated with adalimumab, etanercept, infliximab or ustekinumab were extracted from a prospective cohort. TEs with high clinical responses were described. Uni- and multivariate regression analyses were performed with the generalized estimating equation method to elucidate which baseline patient characteristics were predictors for PASI 90 and PASI ≤ 5 at week 24. RESULTS: In total, 454 TEs were extracted (159 adalimumab; 193 etanercept; 19 infliximab; 83 ustekinumab) from 326 patients. At week 24, in 3%, 15% and 59% of TEs, respectively, PASI 100, PASI 90 and PASI ≤ 5 was reached. In TEs without a PASI 100 or PASI 90 response, PASI ≤ 5 was still achieved in 58% and 52%, respectively. Baseline PASI ≥ 10 was a strong predictor for achieving PASI 90; baseline PASI < 10 and a lower baseline body mass index (BMI) were significant predictors for PASI ≤ 5 at week 24. CONCLUSIONS: A limited number of patients achieved PASI 100 or PASI 90 at 24 weeks of biological treatment. Including an absolute PASI score in the assessment of psoriasis severity is important. Baseline BMI was an important, modifiable predictor for a high response.


Assuntos
Fatores Biológicos/uso terapêutico , Psoríase/tratamento farmacológico , Adalimumab/uso terapêutico , Etanercepte/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/uso terapêutico
5.
Br J Dermatol ; 176(4): 1001-1009, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27579864

RESUMO

BACKGROUND: The efficacy of etanercept and ustekinumab in psoriasis has been compared in one randomized controlled trial. Comparison of the long-term effectiveness of biologics in daily-practice psoriasis treatment is currently lacking. OBJECTIVES: To compare the effectiveness between the three widely used outpatient biologics adalimumab, etanercept and ustekinumab in daily-practice psoriasis treatment and to correct for confounders. METHODS: Data were extracted from the prospective, multicentre BioCAPTURE registry. Multilevel linear regression analyses (MLRAs) and generalized estimating equation (GEE) analyses were performed on the course of mean Psoriasis Area and Severity Index (PASI) and PASI 75 (≥ 75% reduction vs. baseline). Both models were corrected for confounders. Subgroup analyses for biological dose were performed. RESULTS: We included 356 patients with 513 treatment episodes: 178 adalimumab, 245 etanercept and 90 ustekinumab. MLRA showed a similar effectiveness between adalimumab, etanercept and ustekinumab after 1 year, but the highest effectiveness for ustekinumab during 5 years of treatment (P = 0·047; ustekinumab vs. etanercept, P = 0·019). GEE analysis revealed a higher chance of attaining PASI 75 with adalimumab and ustekinumab than with etanercept at 1 year of treatment. A higher than label dose was more often used in patients treated with etanercept (adalimumab, etanercept and ustekinumab: respectively 31·5%, 55·1% and 17% after 1 year, P < 0·001; 39·3%, 71·4% and 24% after 5 years, P < 0·001). CONCLUSIONS: Compared with etanercept, ustekinumab had the highest effectiveness during 5 years of treatment. Patients receiving adalimumab and ustekinumab more often reached PASI 75 than those on etanercept at 1 year of treatment. Dose escalation was more frequent in etanercept and adalimumab than in ustekinumab.


Assuntos
Adalimumab/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Etanercepte/administração & dosagem , Psoríase/tratamento farmacológico , Ustekinumab/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Índice de Gravidade de Doença , Resultado do Tratamento
6.
Br J Dermatol ; 175(2): 340-7, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26989852

RESUMO

BACKGROUND: Predictors for successful treatment are important for personalized medicine. Predictors for drug survival of biologics in psoriasis have been assessed, but not split for different biologics or for the reason of discontinuation. OBJECTIVES: To compare long-term drug survival between the outpatient biologics adalimumab, etanercept and ustekinumab in patients with psoriasis, and to elucidate predictors for overall survival and drug discontinuation due to ineffectiveness and side-effects for each biologic separately. METHODS: Ten years of data were extracted from the prospective, multicentre, long-term BioCAPTURE registry. Kaplan-Meier survival analyses and confounder-corrected multivariate Cox regression analysis for drug survival (MCR-DS) were performed to compare drug survival between biologics. To elucidate the predictors for different reasons of discontinuation for each biologic, univariate Cox regression analyses and multivariate Cox regression analyses for predictors (MCR-P) with backward selection were performed. RESULTS: In total, 526 treatment episodes - 186 adalimumab, 238 etanercept and 102 ustekinumab - were included covering 1333 treatment years. MCR-DS showed a significantly higher overall survival for ustekinumab compared with adalimumab and etanercept. MCR-P showed that higher body mass index (BMI) was a predictor for discontinuation due to ineffectiveness for etanercept and ustekinumab and that female sex was a predictor for discontinuation due to side-effects for adalimumab, etanercept and ustekinumab. CONCLUSIONS: Ustekinumab has the highest confounder-corrected long-term drug survival in psoriasis treatment, compared with adalimumab and etanercept. Higher BMI is a predictor for discontinuation due to ineffectiveness in etanercept and ustekinumab, and female sex is a consistent predictor for discontinuation due to side-effects in all three outpatient biologics.


Assuntos
Adalimumab/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Etanercepte/efeitos adversos , Psoríase/tratamento farmacológico , Ustekinumab/efeitos adversos , Adalimumab/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Fatores Biológicos/efeitos adversos , Índice de Massa Corporal , Esquema de Medicação , Substituição de Medicamentos , Etanercepte/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Caracteres Sexuais , Ustekinumab/administração & dosagem
7.
J Eur Acad Dermatol Venereol ; 29(3): 560-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25088451

RESUMO

BACKGROUND: Drug survival is an indicator for treatment success; insight in predictors associated with drug survival is important. OBJECTIVES (I): To analyse the long-term drug survival for adalimumab in patients with psoriasis treated in daily practice and (II) to identify predictors of prolonged drug survival for adalimumab split for different reasons of discontinuation. METHODS: Data were extracted from a prospective psoriasis cohort and analysed using Kaplan-Meier survival curves split for reasons of discontinuation. Baseline predictors associated with longer drug survival were identified using multivariate Cox-regression analysis. RESULTS: One hundred and sixteen patients were included with a total of 208 patient-years. Overall drug survival was 76% after 1 year and 52% after 4.5 years. In patients who stopped due to ineffectiveness, longer drug survival was associated with the absence of specific comorbidities (P = 0.03). In patients who stopped due to side-effects, longer drug survival was associated with male gender (P = 0.02). CONCLUSIONS: Predictors of adalimumab drug survival in psoriasis differ by reason for discontinuation. Strong, specific predictors can lead to patient-tailored treatment.


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
8.
J Eur Acad Dermatol Venereol ; 29(4): 752-60, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25229823

RESUMO

BACKGROUND: Concerns exist about a risk of non-melanoma skin cancer (NMSC) in psoriasis patients and rheumatoid arthritis (RA) patients treated with TNF-inhibitors. However, current data also show that in some psoriasis patients, NMSC is diagnosed relatively short after the start of TNF-inhibitors, which suggests that these NMSC can be explained by previous therapies instead of by TNF-inhibitor therapy. OBJECTIVE: To investigate whether there was a difference in time until first NMSC and the rate of NMSC between psoriasis and RA patients on TNF-inhibitors. METHODS: Time until first NMSC and the rate of NMSC were compared between psoriasis and RA patients from the same region treated with TNF-inhibitors and followed up for at least one year in prospective cohort studies, by using Cox regression and Poisson regression. Both analyses were corrected for confounders (age, gender, disease duration, prior NMSC, duration of anti-TNF and other systemic therapies). RESULTS: The NMSC risk was significantly higher in the psoriasis group [fully adjusted HR 6.0 (1.6-22.4 95%CI)] with a shorter time until first NMSC in psoriasis compared to RA. By Poisson regression, psoriasis patients had a 5.5 (2.2-13.4 95%CI) higher rate of NMSC. CONCLUSION: The time until first NMSC was significantly shorter and the rate of NMSC was significantly higher in psoriasis compared with RA. This indicates that disease-related factors like phototherapy may be important contributing factors to NMSC diagnosed in psoriasis patients treated with TNF-inhibitors.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Psoríase/tratamento farmacológico , Neoplasias Cutâneas/epidemiologia , Adalimumab/uso terapêutico , Adulto , Idoso , Etanercepte/uso terapêutico , Feminino , Seguimentos , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fototerapia , Fatores de Risco , Fatores de Tempo , Fator de Necrose Tumoral alfa/antagonistas & inibidores
9.
Br J Dermatol ; 171(5): 1189-96, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24807471

RESUMO

BACKGROUND: Drug survival is a marker for treatment success. To date, no analyses relating dermatological quality-of-life measures to drug survival have been published. OBJECTIVES: (i) To describe 1-year drug survival for adalimumab, etanercept and ustekinumab in a daily practice psoriasis cohort, and (ii) to introduce the concept of 'happy' drug survival, defined as Dermatology Life Quality Index (DLQI) ≤ 5 combined with being 'on drug' at a specific time point. METHODS: Data were extracted from a prospective registry. Drug survival was analysed using Kaplan-Meier estimates. 'Happy' drug survival was calculated, with data split into 'happy' (DLQI ≤ 5) vs. 'unhappy' (DLQI > 5) at baseline and months 3, 6, 9 and 12. RESULTS: 249 treatment episodes were included (101 adalimumab, 82 etanercept, 66 ustekinumab). The 1-year drug survival rates for ustekinumab, adalimumab and etanercept were 85%, 74% and 68%, respectively. Ustekinumab showed a better confounder-corrected drug survival vs. etanercept [hazard ratio (HR) 3·8, P = 0·02] and a trend towards better survival vs. adalimumab (HR 2·3, P = 0·1). At baseline, the majority (n = 115, 73%) was considered 'unhappy' and a minority 'happy' (n = 42, 27%) (ratio 'happy':'unhappy' was 1 : 2.7). The percentage of treatment episodes with 'happy' on-drug patients increased to 79% after 1 year. CONCLUSIONS: Ustekinumab showed a better overall drug survival than etanercept, and a trend towards a better overall drug survival than adalimumab. After 1 year, patients reported to be 'happy' in 79% of episodes and 'unhappy' in 21%. We introduced the new concept of 'happy' drug survival because the proportion of on-drug patients with good quality of life is an important indicator for treatment success.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Imunoglobulina G/uso terapêutico , Psoríase/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab , Substituição de Medicamentos , Etanercepte , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Ustekinumab
10.
Br J Dermatol ; 170(2): 415-24, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24117023

RESUMO

BACKGROUND: Long-term data of etanercept drug survival in patients with psoriasis in daily practice are scarce. OBJECTIVES: The primary objective was to describe drug survival for etanercept in a long-term daily practice cohort of patients with psoriasis. The secondary objective was to identify determinants of drug survival for etanercept in general and separately for discontinuation due to adverse events or ineffectiveness of therapy. METHODS: Data were extracted from a prospective daily practice cohort of patients treated with biologics for psoriasis. Drug survival was analysed by Kaplan-Meier survival curves and split for two reasons for discontinuation: adverse events and ineffectiveness. Determinants of drug survival were analysed using univariate Cox regression analysis and multivariate Cox regression analysis with backward selection. RESULTS: We included 193 patients (512 patient-years treated) with a maximum treatment duration of 7·5 years. The overall drug survival rates were 77%, 41% and 30% after 1, 4 and 7·5 years, respectively. The mean survival duration was 3·8 years (95% confidence interval 3·4-4·3). Reasons for discontinuation were ineffectiveness (33·7%), adverse events (11·9%), both ineffectiveness and adverse events (4·7%) or other reasons (e.g. pregnancy planned) (5·7%). Determinants related to longer general drug survival were male sex [hazard ratio (HR) 0·55], prior anti-tumour necrosis factor (TNF)-α use (HR 0·57) and lower etanercept dose (HR 0·65). Younger age (HR 0·83), lower body mass index (HR 0·63) and lower etanercept dose (HR 0·71) were related to a decreased risk of discontinuation due to side-effects. A lower mean weekly dose of etanercept (HR 0·63) was related to a decreased risk of discontinuation due to ineffectiveness of therapy. CONCLUSIONS: We present the longest analysis of drug survival for etanercept in psoriasis to date. Determinants of longer overall etanercept drug survival were male sex, prior anti-TNF therapy and lower etanercept dose. The determinants of longer drug survival depended on the reason for discontinuation of etanercept.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Imunoglobulina G/administração & dosagem , Fatores Imunológicos/administração & dosagem , Psoríase/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/administração & dosagem , Esquema de Medicação , Etanercepte , Feminino , Humanos , Estimativa de Kaplan-Meier , Assistência de Longa Duração , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
11.
J Eur Acad Dermatol Venereol ; 28(1): 27-33, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23216663

RESUMO

BACKGROUND: Auto-immune inflammatory rheumatic diseases (AIRD) are often successfully treated with the immunosuppressant azathioprine for years. Treatment with azathioprine has been proven to increase the risk of non-melanoma skin cancer (NMSC) in transplant patients and possibly in patients with inflammatory bowel disease as well. Little is known about the risk of NMSC in AIRD patients treated with azathioprine. OBJECTIVES: The aim of this study is to determine the incidence of NMSC in patients with AIRD treated with azathioprine for at least 1 year, as compared with the general Dutch population. METHODS: Data were extracted from a historical cohort of patients with AIRD in a tertiary care centre. We compared the incidence to an age-matched control population and analysed risk factors for NMSC with univariate logistic regression. RESULTS: Fifty-nine patients were analysed. No patients were diagnosed with basal cell carcinoma and four patients with a single squamous cell carcinoma (SCC). Patients with SCC had a higher cumulative dose of azathioprine (≥ 500 g: OR 30.0 [95% CI 2.6-345.1]) and longer treatment duration (≥ 11 years: OR 13.5 [95% CI 1.3-143.6]). The risk of SCC compared with the general Dutch population was increased (standardized incidence ratio of 16.0 [95% CI 0.3-31.7]). CONCLUSIONS: In this cohort of patients with AIRD treated with azathioprine for at least 1 year, the risk of SCC was increased, as compared with the general population. An individual cumulative dose of at least 500 g azathioprine and a treatment duration of at least 11 years were quantified as risk factors.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Azatioprina/administração & dosagem , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Azatioprina/uso terapêutico , Carcinoma de Células Escamosas/induzido quimicamente , Criança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/induzido quimicamente , Adulto Jovem
12.
J Eur Acad Dermatol Venereol ; 27(5): 593-600, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22416818

RESUMO

BACKGROUND: Patients and the course of treatment in daily practice are different from randomized controlled trials (RCTs). PRIMARY OBJECTIVE: to analyse the percentage of patients achieving PASI 75. SECONDARY OBJECTIVES: PASI 50, PASI 90, PASI 100 responses, the percentage of patients experiencing at least one serious adverse event (SAE) and the response in biologic-naïve vs. non-naïve patients. METHODS: Prospectively collected efficacy and safety data of a cohort of psoriasis patients treated with adalimumab in daily practice between May 2007 and July 2011 were analyzed. Efficacy was determined using an intention-to-treat analysis and an as treated analysis, in comparison with the course baseline PASI before the start of adalimumab and the original baseline PASI before the start of any biologic therapy. RESULTS: Eighty-five patients received adalimumab therapy with a mean treatment duration of 1.4 (range 0.02-3.1) years. Compared with the original baseline PASI, PASI 75 response rates at week 12 and 24 were 34% and 38% (ITT). PASI 75 responses were well maintained until week 132. Only the PASI 75 response rate at week 12 differed significantly between biologic-naïve (56%) and non-naïve patients (29%). Sixteen patients (19%) experienced 28 SAEs. Seven patients (8%) experienced SAEs considered possibly or probably related to adalimumab. CONCLUSIONS: In this cohort, PASI75 responses were substantial but lower than in RCTs and other daily practice studies. Efficacy was well maintained during more than 2 years of follow-up and differed only between biologic-naïve and non-naïve patients at week 12. The incidence of SAEs was low but seems higher than observed in RCTs.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Adalimumab , Anticorpos Monoclonais Humanizados/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Humanos , Estudos Prospectivos
14.
J Eur Acad Dermatol Venereol ; 26(3): 283-91, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21435026

RESUMO

BACKGROUND: The cumulative exposition to biologics is increasing with prolonged treatment with a certain biologic or consecutive biological treatment. However, long-term safety data are limited available. OBJECTIVES: The aim of this study was to prospectively evaluate the 5-year safety of biological treatment for psoriasis in daily practice. METHODS: A cohort of 173 psoriasis patients on biologics was prospectively followed for 5 years. All adverse events reported were documented and analysed. Primary endpoint was the percentage of patients reporting at least one serious adverse event. The rate of malignancies, serious infections and serious cardiovascular events was compared with the general population incidence rate. The nature and rate of dermatological adverse events was compared with a group of prospectively followed rheumatoid arthritis patients on TNF-α blocking therapy. RESULTS: Between February 2005 and April 2010, 173 patients were enrolled in the registry and went through a total number of 263 treatment episodes. The total number of patient-years of follow-up in the registry was 409. The number of patient-years was the highest for etanercept. Forty-nine patients (28%) reported 88 serious adverse events. Only one serious adverse event was certainly causally related to the biologic and 21 events (24% of SAEs) were considered possibly related. The incidence of malignancies, serious infections and serious cardiovascular events was comparable with the population incidence rate, except for skin malignancies. The incidence of skin malignancies was significantly higher than the general population incidence rate. The nature and rate of dermatological adverse events differed from the rheumatoid arthritis cohort. CONCLUSIONS: In this cohort, the safety of biological therapies for psoriasis was favourable with a low incidence of therapy-related serious adverse events.


Assuntos
Produtos Biológicos/uso terapêutico , Psoríase/tratamento farmacológico , Idoso , Produtos Biológicos/efeitos adversos , Biomarcadores/sangue , Comorbidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Distribuição de Poisson , Estudos Prospectivos , Sistema de Registros , Resultado do Tratamento
15.
Br J Dermatol ; 165(2): 375-82, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21428975

RESUMO

BACKGROUND: Guidelines concerning biological treatment of patients with psoriasis recommend different pretreatment and monitoring laboratory panels in variable frequencies to monitor treatment. OBJECTIVES: To investigate the relevance of laboratory investigations in monitoring patients with psoriasis on etanercept or adalimumab. METHODS: A prospective cohort study over 5 years was conducted in all consecutive patients with psoriasis on etanercept or adalimumab. All laboratory investigations performed for monitoring treatment were analysed. Laboratory abnormalities were graded according to the Common Terminology Criteria for Adverse Events v4.03. The primary endpoint was the percentage of patients with a grade 3 or grade 4 laboratory abnormality. The secondary endpoints were defined as: (i) significant changes in laboratory parameters during etanercept or adalimumab treatment and (ii) the percentage of patients having a laboratory abnormality requiring discontinuation of etanercept or adalimumab treatment. RESULTS: Laboratory parameters were available for 162 patients treated with etanercept and/or adalimumab. The number of treatment episodes was 155 for etanercept and 58 for adalimumab. Follow-up was 316 patient-years for etanercept and 54 patient-years for adalimumab. Thirty-eight of 146 patients treated with etanercept (26%) had one or more grade 3 and/or grade 4 laboratory abnormalities. For adalimumab, this was eight of 58 (14%). These were predominantly considered unrelated to biologic therapy. For both biologics, significant changes were observed in mean laboratory parameters during treatment compared with pretreatment as well as significant trends. However, mean values during treatment remained within normal ranges. Laboratory abnormalities did not lead to permanent discontinuation of biologic treatment in any patient. CONCLUSIONS: In this cohort, the incidence of biologic therapy-related serious laboratory abnormalities was low. Our findings do not support a need for routine laboratory testing in patients with psoriasis on etanercept or adalimumab beyond the laboratory testing required for concomitant therapies or comorbidities.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Monitoramento de Medicamentos/métodos , Imunoglobulina G/efeitos adversos , Psoríase/tratamento farmacológico , Adalimumab , Adulto , Anticorpos Antinucleares/metabolismo , Anticorpos Monoclonais Humanizados , Proteína C-Reativa/metabolismo , Técnicas de Laboratório Clínico/estatística & dados numéricos , Etanercepte , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores do Fator de Necrose Tumoral
16.
Br J Dermatol ; 163(4): 838-46, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20649798

RESUMO

BACKGROUND: Knowledge on the sequential treatment of psoriasis with biologics with regard to efficacy and safety is sparse. This also applies to the efficacy and safety of adalimumab in patients previously treated with etanercept. The relationship between the reasons for discontinuation of etanercept and the response to adalimumab is not clear in psoriasis. OBJECTIVES: To evaluate the efficacy and safety of adalimumab in patients with psoriasis with primary failure, secondary failure or intolerance to etanercept in daily practice. METHODS: Data were extracted from two prospective registries from all patients with psoriasis with failure on etanercept treatment, who switched to adalimumab therapy. Thirty patients fulfilled these criteria. All patients were naive to biologics when etanercept was initiated. Primary endpoints were the percentage of patients achieving a 50% or 75% improvement of the baseline Psoriasis Area and Severity Index (PASI) score (PASI 50 and PASI 75, respectively) at weeks 12, 24 and 48. Secondary endpoints were the percentage of patients achieving PASI 90, the mean percentage improvement in the PASI score from baseline and the adverse event rate. RESULTS: Compared with the baseline PASI score before the start of etanercept, the mean percentage improvement in PASI and the PASI 50/75/90 response rates to adalimumab until week 48 were comparable to those achieved with etanercept. In the patients failing on etanercept, PASI 75 was achieved by 27%, 36% and 54% at weeks 12, 24 and 48 of adalimumab treatment, respectively. The majority of patients showed a beneficial response to adalimumab, irrespective of the reason for discontinuation of etanercept. Previous treatment with etanercept did not increase the adverse event rate nor change the nature of the side-effects. CONCLUSIONS: Adalimumab seems to be an effective and safe treatment option for patients with psoriasis who failed on etanercept treatment irrespective of the reason for discontinuation.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Imunoglobulina G/uso terapêutico , Imunossupressores/uso terapêutico , Psoríase/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Fármacos Dermatológicos/efeitos adversos , Etanercepte , Feminino , Humanos , Imunoglobulina G/efeitos adversos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Falha de Tratamento , Resultado do Tratamento
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