RESUMO
Psoriatic disease is a chronic, systemic immune-mediated inflammatory disorder comprising three major domains, skin, vascular and bone/joint inflammation. It is known for a long time that psoriatic disease is associated with a number of conditions such as hypertension, dyslipidemia, diabetes (metabolic syndrome) and depression. Up to one out of five people with psoriasis show concomitant depression. In the past, this was attributed to psychological stress of suffering from a chronic condition that is often visible and itchy, leading to stigmatization and adding to a significant burden of disease. Recent data provide evidence that depression associated with psoriatic disease is linked to the specific inflammatory pattern with IL-23, IL-17 family cytokines, TNF, IL-6 and IL-8 causing neuroinflammation and subsequently depression or depressive behaviour and/or anxiety. Psoriatic disease shows a distinct pattern of immune cells (e.g. dendritic cells, Th17 cells, neutrophils), mediators (e.g. IL-17A/F, IL-23, TNF) and tissue-related factors in all major domains that is different from other inflammatory dermatoses. There is a striking similarity between the inflammatory pattern in psoriatic disease and neuroinflammation that leads to depression. A number of risk factors have been identified in psoriatic disease, the most important of which are obesity and tobacco smoking. Obesity is known as a major risk factor for depression and anxiety due to its inflammatory signature. Apart from psychotherapy and anti-depressive medication, targeted treatments for psoriasis, including TNF, IL-17 and IL-23 inhibitors, can improve depression/depressive symptoms. The review summarizes the current knowledge about depression as a comorbidity in psoriatic disease.
Assuntos
Artrite Psoriásica , Psoríase , Humanos , Interleucina-17/metabolismo , Depressão/epidemiologia , Doenças Neuroinflamatórias , Psoríase/complicações , Psoríase/epidemiologia , Psoríase/tratamento farmacológico , Comorbidade , Inflamação/epidemiologia , Inflamação/complicações , Obesidade/complicações , Interleucina-23 , Artrite Psoriásica/diagnósticoRESUMO
BACKGROUND: Brodalumab is a monoclonal antibody that blocks multiple interleukin (IL)-17 family cytokines by binding to the shared A subunit of the IL-17 receptor. In Phase 3 trials, brodalumab provided high levels of skin clearance through 52 weeks in patients with moderate-to-severe psoriasis and was generally well tolerated. OBJECTIVES: To assess efficacy response rates and safety outcomes through 120 weeks for patients with moderate-to-severe psoriasis who received brodalumab. METHODS: Safety and efficacy data were pooled for patients from AMAGINE-2 and -3 who received continuous brodalumab 210 mg every 2 weeks, or brodalumab 210 mg every 2 weeks after receiving either brodalumab 140 mg or placebo through Week 12. Efficacy data are presented using observed data, non-responder imputation (NRI) and a combination of NRI and missing at random assumption to account for missing data. Absolute PASI scores are presented using mixed-effect model repeated measure modelling and multiple imputation. RESULTS: Based on observed data at Week 120, 86% of the continuous brodalumab 210 mg group achieved PASI 90 and 74% achieved PASI 100. At Week 12, 58% of this group achieved absolute PASI ≤1; this proportion increased to approximately 80% at Week 52 and persisted through Week 120. Among patients receiving continuous brodalumab 210 mg, median duration of brodalumab exposure was 747 days and the overall exposure-adjusted event rate of treatment emergent adverse events per 100 patient-years was 329. Safety through 120 weeks was comparable to the results of the primary AMAGINE-2 and -3 studies. Patients who switched to brodalumab 210 mg after receiving either brodalumab 140 mg or placebo through Week 12 showed similar skin clearance and safety profiles. CONCLUSIONS: Brodalumab treatment was well tolerated and resulted in high levels of skin clearance that were rapidly achieved and maintained through Week 120, supporting its long-term efficacy and safety profile.
Assuntos
Psoríase , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-Cego , Humanos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Treating to absolute treatment targets rather than relative measures such as Psoriasis Area and Severity Index (PASI)-75 is emerging as an important clinical concept included in psoriasis guidelines and clinical practice. Achieving treatment targets is associated with achievement of long-term outcomes. OBJECTIVE: To evaluate the relationship between psoriasis severity, disease characteristics and achievement of PASI ≤2 with apremilast in a pooled analysis of the phase 3 ESTEEM 1 and 2 (NCT01194219 and NCT01232283), phase 3b LIBERATE (NCT01690299) and phase 4 UNVEIL (NCT02425826) clinical trials. METHODS: Pooled data from patients with moderate-to-severe plaque psoriasis randomized to apremilast 30 mg BID were analysed by baseline PASI quartiles (Q1: 2.4-13.1; Q2: 13.2-15.9; Q3: 16.0-20.0; Q4: 20.1-57.8). Assessments included PASI, Dermatology Life Quality Index (DLQI), Scalp Physician's Global Assessment (ScPGA; ScPGA ≥1) and target (worst) Nail Psoriasis Severity Index (NAPSI; NAPSI ≥1). RESULTS: Of 1062 patients, 963 had ScPGA ≥1 and 643 had NAPSI ≥1; 771 patients with baseline and Week 32 PASI assessments were included in analyses of Week 32 PASI target achievement. Rates of PASI ≤2 at Week 32 were greater in lower PASI quartiles (Q1: 43.5%; Q2: 31.2%; Q3: 26.8%; Q4: 18.4%). Most patients achieving PASI ≤2 target (83.6%) achieved DLQI ≤5 at Week 32; 59.3% of patients who did not achieve PASI ≤2 target achieved DLQI ≤5. At Week 32, mean improvements in ScPGA and NAPSI were similar with more moderate vs. more severe disease (ScPGA, range: 1.1-1.4; NAPSI, range: 1.6-2.5). In a subgroup analysis, achievement of PASI ≤2 target was higher in the lowest PASI quartile and with disease duration <5 years. CONCLUSIONS: Greater achievement of PASI ≤2 was observed in patients with more moderate vs. more severe skin disease. Apremilast may be particularly beneficial in more moderate disease early in the treatment paradigm.
Assuntos
Doenças da Unha , Psoríase , Ensaios Clínicos Fase III como Assunto , Humanos , Psoríase/tratamento farmacológico , Qualidade de Vida , Índice de Gravidade de Doença , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Resultado do TratamentoRESUMO
Systemic treatment together with radical surgical excision is the most important treatment option for all severity grades of hidradenitis suppurativa. Tetracycline in mild-to-moderate forms and clindamycin in combination with rifampicin in moderate-to-severe forms are guideline-compliant first-line therapy with a good clinical response. Other antibiotics such as ertepenem or multiple combinations are recommended as last-line therapy due to a lack of data. Success rate with dapsone and retinoids, on the other hand, are insufficient-only acitretin can be recommended on the basis of the available studies, but with limited success. With the TNF-alpha blocker adalimumab, an effective and safe long-term therapy is available-further biologics are in clinical trials and could significantly expand the treatment portfolio in the future.
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Produtos Biológicos , Hidradenite Supurativa , Adalimumab , Antibacterianos/uso terapêutico , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/tratamento farmacológico , Humanos , Retinoides/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Assessment of psoriasis is exclusively done measuring severity using somatic scores such as the psoriasis area and severity index or patient-reported outcomes such as the dermatology life quality index. There is no established tool to measure a patient's individual psoriasis activity over time. OBJECTIVES: Development of a new tool to classify psoriasis activity types. METHODS: Open patient interviews were performed and adapted in several steps and by using different groups of patients. Wording of the tool's axis and description how to use it was optimized with the input of patients. The final ActiPso tool was used in a prospective study in psoriasis patients. RESULTS: Four activity types could be identified describing psoriasis intensity (e.g. severity, itch, pain) over one typical year and an event/trigger type describing flares. In the study in 586 psoriasis patients of the 536 patients eligible for analysis 40.9% self-classified as type 1 ('stable'), 22.6% as type 2 ('unstable'), 30.6% as type 3 ('winter type') and 6.0% as type 4 ('summer type'), respectively. Flares of psoriasis as identified by the event/trigger type were reported in 36.1% of patients with activity type 1, 67.8% with type 2, 73.8% of type 3 and 59.4% of type 4, respectively. CONCLUSIONS: Interviewed patients were able to describe their course of psoriatic disease and to name potential triggering factors. By doing so, activity types of psoriasis were defined for the first time and the importance of events/triggers for flares described and integrated into ActiPso types as a basis for advanced patient-centric management. A limitation of ActiPso is that in regions with no seasonal variations types 3 and 4 may not apply.
Assuntos
Artrite Psoriásica , Psoríase , Humanos , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Few systematic data on sex-related treatment responses exist for psoriasis. OBJECTIVES: To evaluate sex differences with respect to systemic antipsoriatic treatment. METHODS: Data from patients with moderate-to-severe psoriasis in the PsoBest or Swiss Dermatology Network of Targeted Therapies (SDNTT) registries were analysed. Treatment response was defined as achieving a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) or PASI ≤ 3 at treatment months 3, 6 and 12, supplemented by patient-reported outcomes [i.e. Dermatology Life Quality Index (DLQI) ≤ 1 and delta DLQI ≥ 4]. RESULTS: In total, 5346 patients registered between 2007 and 2016 were included (PsoBest, n = 4896; SDNTT, n = 450). The majority received nonbiological treatment (67·3% male, 69·8% female). Women showed slightly higher PASI response rates after 3 (54·8% vs. 47·2%; P ≤ 0·001), 6 (70·8% vs. 63·8%; P ≤ 0·001) and 12 months (72·3% vs. 66·1%; P ≤ 0·004). A significantly higher proportion of women achieved a reduction in DLQI ≥ 4 [month 3: 61·4% vs 54·8% (P ≤ 0·001); month 6: 69·6% vs. 62·4% (P ≤ 0·001); month 12: 70·7% vs. 64·4% (P ≤ 0·002)]. Regarding PASI ≤ 3, women on biologics showed a significantly superior treatment response compared with men at 3 (57·8% vs. 48·5%; P ≤ 0·004) and 6 months (69·2% vs. 60·9%; P ≤ 0·018). Women in the nonbiological treatment group had a significantly better treatment response (PASI response, PASI 75 and PASI ≤ 3) over 12 months compared with men. CONCLUSIONS: We provide evidence that women experience better treatment outcomes with systemic antipsoriatic therapy than men.
Assuntos
Fármacos Dermatológicos , Psoríase , Fármacos Dermatológicos/uso terapêutico , Feminino , Humanos , Masculino , Estudos Prospectivos , Psoríase/tratamento farmacológico , Qualidade de Vida , Sistema de Registros , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Dimethyl fumarate (DMF) is a treatment for moderate-to-severe psoriasis and multiple sclerosis. DMF therapy typically improves skin inflammation within the first 3 months of treatment. DMF is a prodrug that generates the hydroxycarboxylic acid receptor 2 (HCA2) agonist, monomethyl fumarate (MMF). Despite widespread clinical use, DMF's mechanism of action is not fully understood. OBJECTIVES: We wished to characterize the changes induced by DMF in peripheral neutrophils within the first 3 months of treatment to better understand its early antipsoriatic effects. METHODS: Flow cytometry was used to assess T-cell and neutrophil frequencies, apoptosis and activation phenotype. In vitro culture of neutrophils with DMF and MMF was used to evaluate apoptosis and HCA2 internalization. Serum levels of neutrophil degranulation products were measured by enzyme-linked immunosorbent assay. RESULTS: Patients with psoriasis had significantly higher leucocyte counts at baseline compared with controls, with a large population of pro-inflammatory CD62Llo CD11bbright neutrophils. Analysis revealed that DMF treatment reduced the frequency of CD62Llo CD11bbright neutrophils and serum levels of neutrophil activation markers. This reduction was not linked to increased apoptosis. CONCLUSIONS: Our results reveal a novel in vivo effect of DMF therapy on pro-inflammatory neutrophils that likely contributes to this treatment's antipsoriatic efficacy.
Assuntos
Fármacos Dermatológicos , Esclerose Múltipla , Psoríase , Fumarato de Dimetilo , Humanos , Neutrófilos , Psoríase/tratamento farmacológicoRESUMO
BACKGROUND: In the study series PsoHealth first data from 2004/05 showed a poor quality of health care for psoriasis in Germany. Most patients lacked sufficient care and only a minor proportion received systemic drugs. Since 2007, a national psoriasis programme has been conducted. OBJECTIVES: (1) To analyse the quality of health care for psoriasis in the most recent PsoHealth4 survey 2016/17, (2) to compare health care quality indicators with prior assessments since 2004/05. MATERIALS AND METHODS: The recent cross-sectional PsoHealth4 survey was conducted 2016/17, and three preceding studies were performed in 2004/05, 2007 and 2013/14, each including at least 1500 patients. The common set of quality indicators included disease severity (PASI and proportion of patients with PASI > 20, indicating high severity), quality of life (DLQI and proportion of patients with DLQI > 10, indicating strong impairments in quality of life), systemic therapy and inpatient treatment of the last five years. RESULTS: Between December 2015 and December 2017, n = 1827 patients from 93 dermatological centres were included in the most recent survey (mean age: 50.8 ± 14.6 years, 45.2% female). 7.3% showed a PASI > 20, compared to 17.8% in 2004/05. 21.4% reported a DLQI > 10, compared to 34.0% in 2004/05. 57.6% of all participants stated to have received a systemic therapy at least once within the last five years, compared to 32.9% in 2004/05. 18.0% received inpatient hospital treatment at least once within the last five years, compared to 26.9% in 2004/05. CONCLUSION: A remarkable improvement in the health care quality for psoriasis patients in Germany within the past 12 years can be assumed. Major determinants could be the innovation shift which included programmes such as the S3 guideline, a consensus on treatment goals, national health care goals for psoriasis and higher utilisation of innovative drugs.
Assuntos
Psoríase , Qualidade de Vida , Adulto , Idoso , Estudos Transversais , Atenção à Saúde , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Psoríase/epidemiologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: While the risk of tuberculosis (TB) reactivation is adequately documented in relation to TNF-alpha inhibitors (TNFi), the question of what the tuberculosis risk is for newer, non-TNF biologics (non-TNFi) has not been thoroughly addressed. METHODS: We conducted a systematic review of randomized phase 2 and phase 3 studies, and long-term extensions of same, published through March 2019.âOf interest was information pertaining to screening and treating of latent tuberculosis (LTBI) in association with the use of 12 particular non-TNFi. Only rituximab was excluded. We searched MEDLINE and the ClinicalTrial.gov database for any and all candidate studies meeting these criteria. RESULTS: 677 citations were retrieved; 127 studies comprising a total of 34,293 patients who received non-TNFi were eligible for evaluation. Only 80 out of the 127 studies, or 63â%, captured active TB (or at least opportunistic diseases) as potential outcomes and 25 TB cases were reported. More than two thirds of publications (86/127, 68â%) mentioned LTBI screening prior to inclusion of study participants in the respective trial, whereas in only 4 studies LTBI screening was explicitly considered redundant. In 21 studies, patients with LTBI were generally excluded from the trials and in 42 out of the 127 trials, or 33â%, latently infected patients were reported to receive preventive therapy (PT) at least 3 weeks prior to non-TNFi treatment. CONCLUSIONS: The lack of information in many non-TNFi studies on the number of patients with LTBI who were either excluded prior to participating or had been offered PT hampers assessment of the actual TB risk when applying the novel biologics. Therefore, in case of insufficient information about drugs or drug classes, the existing recommendations of the German Central Committee against Tuberculosis should be applied in the same way as is done prior to administering TNFi. Well designed, long-term "real world" register studies on TB progression risk in relation to individual substances for IGRA-positive cases without prior or concomitant PT may help to reduce selection bias and to achieve valid conclusions in the future.
Assuntos
Produtos Biológicos , Tuberculose Latente , Tuberculose , Produtos Biológicos/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Programas de Rastreamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Fator de Necrose Tumoral alfaRESUMO
This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arthritis, concomitant inflammatory bowel disease, a history of malignancies or a history of depression or suicidal ideation. It further holds recommendations for concomitant diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or patients with a wish for a child in the near future. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.
Assuntos
Psoríase/complicações , Psoríase/terapia , Humanos , Psoríase/psicologiaRESUMO
BACKGROUND: In practice, the goal of treatment for patients with psoriasis is to achieve almost clear or clear skin and maintain disease control, regardless of baseline disease severity. However, identifying absolute Psoriasis Area and Severity Index (PASI) values for new treatment goals is challenging, as most clinical trials report relative PASI 50, 75, 90 or 100 improvements but rarely absolute PASI values achieved. OBJECTIVE: Our objective was to illustrate a statistical conversion method that was developed to derive absolute PASI values from available clinical trial data on relative PASI improvements. The results of network meta-analyses (NMAs) based on these derived data were then compared with those of NMAs based on the corresponding relative PASI improvement data for selected biologics for moderate-to-severe psoriasis. METHODS: The PASI statistical conversion method was applied to relative PASI improvement data for 11 biologic treatment regimens and placebo at 12 weeks using data from 50 published studies. The respective proportions of patients reaching absolute PASI values ≤1, 2, 3 or 5 were then calculated. Frequentist NMAs (Rücker method) were subsequently used to compare efficacy results across relative and absolute PASI data. RESULTS: The ranking of included treatment regimens for patients achieving absolute PASI 0 to 8 was aligned with results for relative PASI scores (from 100 to 60) at end of induction therapy. Across the range of PASI scores considered, the most effective treatment regimens based on both absolute and relative PASI NMAs were brodalumab 210 mg every 2 weeks and ixekizumab 80 mg every 2 weeks, followed by guselkumab 100 mg every 8 weeks and risankizumab 150 mg every 12 weeks. CONCLUSION: Data generated using this mathematical model will be useful to inform ongoing scientific discussions on treatment goals in the absence of primary absolute PASI data for all available treatments for moderate-to-severe plaque psoriasis.
Assuntos
Produtos Biológicos , Psoríase , Produtos Biológicos/uso terapêutico , Humanos , Metanálise em Rede , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Brodalumab is a fully human monoclonal immunoglobulin IgG2 antibody that binds to the human IL-17 receptor subunit A and by that inhibits the biologic action of IL-17A, IL-17F, IL-17C and IL-17E. Therapy with fumaric acid esters (FAE) is a well established and widely used first-line systemic treatment for subjects with moderate-to-severe plaque psoriasis. OBJECTIVES: To compare brodalumab to FAE in terms of clinical efficacy, patient-reported outcomes and safety in subjects with moderate-to-severe plaque psoriasis who were naïve to systemic treatment. METHODS: Eligible subjects were randomized 1 : 1 to 210 mg brodalumab injections or oral FAE according to product label in this 24-week, open-label, assessor-blinded, multi-centre, head-to-head phase 4 trial. The primary endpoints were having PASI75 and having sPGA score of 0 or 1 (sPGA 0/1). Subjects with missing values for the primary endpoints were considered non-responders. RESULTS: A total of 210 subjects were randomized. 91/105 subjects completed brodalumab treatment and 58/105 subjects completed FAE treatment. At Week 24, significantly more subjects in the brodalumab group compared to the FAE group had PASI75 (81.0% vs. 38.1%, P < 0.001) and sPGA 0/1 (64.8% vs. 20.0%, P < 0.001). In the brodalumab group, the median time to both PASI75 and to PASI90 was significantly shorter than in the FAE group (4.1 weeks vs. 16.4 weeks, and 7.4 weeks vs. 24.4 weeks, respectively, P < 0.0001 for both). The rate of adverse events was lower in subjects treated with brodalumab compared to subjects treated with FAE (616.4 vs. 1195.8 events per 100 exposure years). No new safety signals were detected for brodalumab. CONCLUSIONS: Brodalumab was associated with rapid and significant improvements in signs and symptoms of moderate-to-severe plaque psoriasis, with a superior efficacy profile to what was observed with FAE in systemic-naïve subjects over 24 weeks.
Assuntos
Fumaratos , Psoríase , Administração Oral , Adulto , Anticorpos Monoclonais Humanizados , Fumaratos/uso terapêutico , Humanos , Injeções Subcutâneas , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Fármacos Dermatológicos , Psoríase , Anticorpos Monoclonais Humanizados/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Fumaratos/efeitos adversos , Humanos , Metotrexato/efeitos adversos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A, a cornerstone cytokine in psoriasis, has shown long-lasting efficacy and safety in the complete spectrum of psoriasis manifestations. OBJECTIVES: To report the long-term (2·5-year) efficacy and safety of secukinumab in nail psoriasis. METHODS: TRANSFIGURE, a double-blind, randomized, placebo-controlled, parallel-group, multicentre phase IIIb study in 198 patients, investigated secukinumab 150 mg and 300 mg in patients with moderate-to-severe nail psoriasis. RESULTS: At week 16, the primary endpoint Nail Psoriasis Severity Index (NAPSI) was met, demonstrating superiority of secukinumab to placebo. The effect was sustained over 2·5 years with a large benefit for nail clearance, with mean NAPSI improvement of -73·3% and -63·6% with secukinumab 300 mg and 150 mg, respectively. At 2·5 years, secukinumab demonstrated sustained clinically significant reductions in total mean Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) quality-of-life (QoL) scores of -52·4% and -18·1%, and 70% and 71% of patients achieved a weighted NAPPA Patient Benefit Index global score of ≥ 2 with secukinumab 300 mg and 150 mg, respectively. Patients showed considerable improvements in the EuroQol 5-Dimension health status questionnaire at 2·5 years, reporting a decrease in pain and discomfort. No new safety findings were observed. CONCLUSIONS: Secukinumab demonstrated strong and clinically meaningful efficacy for up to 2·5 years in nail psoriasis, with significant sustained QoL improvements and a favourable safety profile.
Assuntos
Psoríase , Qualidade de Vida , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Humanos , 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) 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.
Assuntos
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
BACKGROUND: Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17A and shows long-lasting efficacy and safety in plaque psoriasis. More evidence is required to optimize secukinumab dosing according to clinical response. OBJECTIVES: GAIN compared the efficacy and safety of secukinumab 300 mg every 2 weeks (q2w) with 300 mg every 4 weeks (q4w) in patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) but not PASI 90 after 16 weeks. METHODS: In total, 772 patients with moderate-to-severe plaque psoriasis received secukinumab 300 mg subcutaneously at baseline and weeks 1, 2, 3 and 4, then q4w until week 16. At week 16, patients with PASI ≥ 75 to PASI < 90 were randomized 1: 1 to continue q4w dosing (n = 162) or switch to q2w (n = 163) to week 32. The primary endpoint was superiority of q2w to q4w dosing for PASI 90 response at week 32. RESULTS: PASI 90 response at week 32 was numerically greater with secukinumab 300 mg q2w than with secukinumab 300 mg q4w in suboptimal responders, but this did not reach statistical significance (64·4% vs. 57·4%; odds ratio 0·64, 95% confidence interval 0·39-1·07; P = 0·087). Although the primary endpoint was not met, absolute PASI was significantly lower at week 32 in q2w vs. q4w patients (2·11 vs. 2·84, P = 0·024). Significantly more patients with q2w vs. q4w dosing showed minimal disease activity (Investigator's Global Assessment score 0 or 1: 73·0% vs. 64·1%, P < 0·05) and improved quality of life (Dermatology Life Quality Index score 0 or 1: 58·9% vs. 50·6%, P < 0·05) at week 32. No new or unexpected safety signals arose. CONCLUSIONS: Most patients achieved PASI 90 response with secukinumab q4w. There was potential benefit of q2w dosing in some suboptimal responders. Continued q4w treatment can improve response even after 16 weeks.
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Psoríase , Qualidade de Vida , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Humanos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The first part of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline. Suggestions for disease severity grading and treatment goals are provided. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs. The treatment options discussed in this guideline are as follows: acitretin, ciclosporin, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab.