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BACKGROUND: Psychological therapies can be effective in reducing symptoms of depression and anxiety in people living with dementia (PLWD). However, factors associated with better therapy outcomes in PLWD are currently unknown. AIMS: To investigate whether dementia-specific and non-dementia-specific factors are associated with therapy outcomes in PLWD. METHOD: National linked healthcare records were used to identify 1522 PLWD who attended psychological therapy services across England. Associations between various factors and therapy outcomes were explored. RESULTS: People with frontotemporal dementia were more likely to experience reliable deterioration in depression/anxiety symptoms compared with people with vascular dementia (odds ratio 2.98, 95% CI 1.08-8.22; P = 0.03) or Alzheimer's disease (odds ratio 2.95, 95% CI 1.15-7.55; P = 0.03). Greater depression severity (reliable recovery: odds ratio 0.95, 95% CI 0.92-0.98, P < 0.001; reliable deterioration: odds ratio 1.73, 95% CI 1.04-2.90, P = 0.04), lower work and social functioning (recovery: odds ratio 0.98, 95% CI 0.96-0.99, P = 0.002), psychotropic medication use (recovery: odds ratio 0.67, 95% CI 0.51-0.90, P = 0.01), being of working age (recovery: odds ratio 2.03, 95% CI 1.10-3.73, P = 0.02) and fewer therapy sessions (recovery: odds ratio 1.12, 95% CI 1.09-1.16, P < 0.001) were associated with worse therapy outcomes in PLWD. CONCLUSIONS: Dementia type was generally not associated with outcomes, whereas clinical factors were consistent with those identified for the general population. Additional support and adaptations may be required to improve therapy outcomes in PLWD, particularly in those who are younger and have more severe depression.
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Demência , Atenção Primária à Saúde , Humanos , Masculino , Feminino , Inglaterra , Idoso , Atenção Primária à Saúde/estatística & dados numéricos , Demência/terapia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Ansiedade/terapia , Ansiedade/epidemiologia , Psicoterapia/estatística & dados numéricos , Psicoterapia/métodos , Depressão/terapia , Depressão/epidemiologia , Resultado do Tratamento , Demência Vascular/terapia , Demência Vascular/psicologia , Demência Frontotemporal/terapia , Demência Frontotemporal/psicologia , Doença de Alzheimer/terapiaRESUMO
AIMS: People with depression are up to 72% more at risk to develop cardiovascular disease (CVD) in their lifetime. Evidence-based psychotherapies are first-line interventions for the treatment of depression and are delivered nationally in England through the National Health Service via the Improving Access to Psychological Therapy (IAPT) primary care programme. It is currently unknown whether positive therapy outcomes may be associated with cardiovascular risk reduction. This study aimed to examine the association between psychotherapy outcomes for depression and incident CVD. METHODS AND RESULTS: A cohort of 636 955 individuals who have completed a course of psychotherapy was built from linked electronic healthcare record databases of national coverage in England: the national IAPT database, the Hospital Episode Statistics (HES) database, and the HES-ONS (Office of National Statistics) mortality database. Multivariable Cox models adjusting for clinical and demographic covariates were run to estimate the association between reliable improvement from depression and the risk of subsequent incidence of cardiovascular events. After a median follow-up of 3.1 years, reliable improvement from depression symptoms was associated with a lower risk of new onset of any CVD [hazard ratio (HR): 0.88, 95% confidence interval (CI): 0.86, 0.89], coronary heart disease (HR: 0.89, 95% CI: 0.86, 0.92), stroke (HR: 0.88, 95% CI: 0.83, 0.94), and all-cause mortality (HR: 0.81, 95% CI: 0.78, 0.84). This association was stronger in the under 60 compared with the over 60 for all outcomes. Results were confirmed in sensitivity analyses. CONCLUSION: Management of depression through psychological interventions may be associated with reduced risk of CVD. More research is needed to understand the causality of these associations.
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Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Depressão/epidemiologia , Depressão/terapia , Medicina Estatal , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , Atenção à SaúdeRESUMO
Nail psoriasis is a chronic, difficult-to-treat condition affecting almost half of patients with psoriasis. It is associated with considerable social stigma and impairment of patients' quality of life. The aim of this study was to assess improvements in objective measures of nail psoriasis among patients from the long-term extension of the UNCOVER-3 study who received the interleukin-17A inhibitor ixekizumab and had either any degree of nail psoriasis (Nail Psoriasis Severity Index (NAPSI) >=1) or significant nail psoriasis (fingernail NAPSI ≥ 16 and ≥ 4 fingernails involved) at baseline. Efficacy outcomes reported through week 264 included the mean percentage improvements from baseline in NAPSI score and the proportion of patients achieving nail psoriasis resolution (NAPSI=0). In UNCOVER-3, 56.9% (219/385) of patients had nail psoriasis at baseline; of those, 61.2% (134/219) had significant nail psoriasis. At week 60, a total of 66.9% and 59.1% of patients with baseline nail psoriasis and significant baseline nail psoriasis, respectively, reported complete clearance of nail psoriasis, an effect which was sustained through week 264. This analysis demonstrates that continuous treatment with ixekizumab in adult patients with moderate-to-severe-psoriasis through 264 weeks was associated with improvements and clearance of fingernail psoriasis, irrespective of the severity of nail psoriasis at baseline.
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Doenças da Unha , Psoríase , Adulto , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Humanos , Interleucina-17 , Doenças da Unha/diagnóstico , Doenças da Unha/tratamento farmacológico , Psoríase/complicações , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
In clinical practice, interruption of treatment may not result in immediate cessation of disease control, and some patients even experience sustained treatment response following treatment interruption. This post hoc analysis of UNCOVER-1 and -2 Phase 3 clinical trials characterized the time to loss of treatment response in patients with psoriasis who responded to ixekizumab through a 12-week treatment period, and who were then re-randomized to placebo for the following 48 weeks. For those with static Physician Global Assessment [sPGA]0/1 and Psoriasis Area and Severity Index [PASI]90 at Week 12, the median time to loss of PASI90 was 16.1 weeks (95% confidence interval 12.7-16.4). For those with PASI100 at Week 12, the median time to loss of PASI100 was 12.1 weeks (95% confidence interval 9.0-13.0). A small subset of patients maintained high levels of disease control through Week 60. This study adds to the growing body of evidence on sustained treatment response following treatment interruption.
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Fármacos Dermatológicos , Psoríase , Anticorpos Monoclonais Humanizados , Humanos , Psoríase/induzido quimicamente , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
PURPOSE: To estimate the risk of dyskinesia and impulse control disorders (ICDs) in patients with Parkinson's disease (PD) prescribed ropinirole prolonged-release (R-PR) compared to those prescribed immediate-release dopamine agonists (IR-DA) as monotherapy. METHODS: PD patients initiating R-PR or IR-DA as monotherapy between 2008 and 2013 were identified on the Clinical Practice Research Datalink. The cohorts were propensity score matched on a 1:1 basis. The incidence of dyskinesia and ICD in each treatment cohort and the incidence rate ratios were calculated. Adherence to medication and time to levodopa initiation were also evaluated. RESULTS: We identified 341 patients in each treatment cohort after propensity score matching. The baseline characteristics were generally comparable. Dyskinesia incidence in R-PR and IR-DA cohorts was 2.98 (95% CI: 0.74-11.9) and 3.93 (95% CI: 0.98-15.7) per 1000 person-years, respectively (incidence rate ratio of R-PR vs ID-DA: 0.76, 95% CI: 0.11-5.38). Less than five cases of ICD were identified and all occurred in the IR-DA cohort. The patients in the R-PR cohort remained on treatment for a significantly longer duration than those in the IR-DA cohort (682 days vs 444 days; P < .0001) and had greater adherence to the medication. The median time to levodopa initiation was 417 days (IQR: 205-736) in R-PR vs 297 days (IQR: 111-552) in IR-DA cohort. CONCLUSIONS: The number of dyskinesia and ICD events was lower than expected, resulting in an underpowered study. A significantly longer persistence and greater adherence to medication was observed in patients receiving R-PR compared to IR-DA.
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Agonistas de Dopamina/uso terapêutico , Discinesias/epidemiologia , Indóis/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Preparações de Ação Retardada , Agonistas de Dopamina/administração & dosagem , Formas de Dosagem , Discinesias/etiologia , Feminino , Humanos , Incidência , Indóis/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Fatores de Risco , Reino Unido/epidemiologiaRESUMO
CORRECTION: After publication of this work [1] it was noticed that the author name Rachael L. DiSantostefano was not spelt correctly as there was a space in her surname between 'Di' and 'Santostefano'. The publisher apologises for this error.
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BACKGROUND: Inhaled corticosteroids (ICS) are the primary treatment for persistent asthma. Currently available ICS have differing particle size due to both formulation and propellant, and it has been postulated that this may impact patient outcomes. This structured literature review and meta-analysis compared the effect of small and standard particle size ICS on lung function, symptoms, rescue use (when available) and safety in patients with asthma as assessed in head-to-head randomized controlled trials (RCTs). METHODS: A systematic literature search of MEDLINE was performed to identify RCTs (1998-2014) evaluating standard size (fluticasone propionate-containing medications) versus small particle size ICS medication in adults and children with asthma. Efficacy outcomes included forced expiratory volume in 1 s (FEV1), morning peak expiratory flow (PEF), symptom scores, % predicted forced expiratory flow between 25 and 75% of forced vital capacity (FEF25-75%), and rescue medication use. Safety outcomes were also evaluated when available. RESULTS: Twenty-three independent trials that met the eligibility criteria were identified. Benefit-risk plots did not demonstrate any clinically meaningful differences across the five efficacy endpoints considered and no appreciable differences were noted for most safety endpoints. Meta-analysis results, using a random-effects model, demonstrated no significant difference between standard and small size particle ICS medications in terms of effects on mean change from baseline FEV1 (L) (-0.011, 95% confidence interval [CI]: -0.037, 0.014 [N = 3524]), morning PEF (L/min) (medium/low doses: -3.874, 95% CI: -10.915, 3.166 [N = 1911]; high/high-medium doses: 5.551, 95% CI: -1.948, 13.049 [N = 749]) and FEF25-75% predicted (-2.418, 95% CI: -6.400; 1.564 [N = 115]). CONCLUSIONS: Based on the available literature, no clinically significant differences in efficacy or safety were observed comparing small and standard particle size ICS medications for the treatment of asthma. TRIAL REGISTRATION: GSK Clinical Study Register No: 202012 .
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Corticosteroides/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Tamanho da Partícula , Administração por Inalação , Volume Expiratório Forçado , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
We used quantitative text analysis to examine conversations in a series of online support groups attended by care partners of people living with rare dementias (PLWRD). We used transcripts of 14 sessions (>100,000 words) to explore patterns of communication in trained facilitators' (n = 2) and participants' (n = 11) speech and to investigate the impact of session agenda on language use. We investigated the features of their communication via Poisson regression and a clustering algorithm. We also compared their speech with a natural speech corpus. We found that differences to natural speech emerged, notably in emotional tone (d = -3.2, p < 0.001) and cognitive processes (d = 2.8, p < 0.001). We observed further differences between facilitators and participants and between sessions based on agenda. The clustering algorithm categorised participants' contributions into three groups: sharing experience, self-reflection, and group processes. We discuss the findings in the context of Social Comparison Theory. We argue that dedicated online spaces have a positive impact on care partners in combatting isolation and stress via affiliation with peers. We then discuss the linguistic mechanisms by which social support was experienced in the group. The present paper has implications for any services seeking insight into how peer support is designed, delivered, and experienced by participants.
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Dementia is a global health concern with increasing numbers of people living long enough to develop dementia. People with dementia (PwD) may be particularly vulnerable to suicidality. However, suicide in PwD has not been thoroughly explored. The objective of this review was to determine the prevalence and risk factors of suicide in PwD. Five databases were searched from inception to July 2023. Peer-reviewed publications reporting prevalence, risk factors or quantitative summary data for suicide outcomes in PwD were included. Random effects models were used to calculate the pooled prevalence and effect sizes. 54 studies met inclusion criteria. In PwD, the point prevalence of suicidal ideation was 10â¯% (95â¯%CI=6â¯%;16â¯%), 2-year period prevalence of suicide attempts was 0.8â¯% (95â¯%CI=0.3â¯%;2â¯%), 10-year period prevalence of suicide attempts was 8.7â¯% (95â¯%CI=6.0â¯%%;12.7â¯%) and the incidence of death by suicide 0.1â¯% (95â¯%CI=0.1â¯%;0.2â¯%). Compared to not having dementia, a diagnosis of dementia increased risk of suicidal ideation (OR=1.62[95â¯%CI=1.17;2.24]) but not risk of suicide attempt (OR=1.77 [95â¯%CI=0.85;3.69]) or death by suicide (OR=1.30 [95â¯%CI=0.81;2.10]). People with moderate dementia had significantly increased risk of suicidal ideation than those with mild dementia (OR=1.59[95â¯%CI=1.11;2.28]), younger PwD were at increased risk of dying by suicide (OR=2.82[95â¯%CI=2.16;3.68]) and men with dementia were more likely to attempt (OR=1.28[95â¯%CI=1.25;1.31]) and die by suicide (OR=2.88[95â¯%CI=1.54;5.39]) than women with dementia. This review emphasises the need for mental health support and suicide prevention in dementia care, emphasising tailored approaches based on age, symptoms, and being male.
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Background: Autistic people are disproportionately likely to experience premature mortality and most mental and physical health conditions. We measured the incidence of diagnosed conditions accounting for the most disability-adjusted life years in the UK population according to the Global Burden of Disease study (anxiety, depression, self-harm, harmful alcohol use, substance use, migraine, neck or back pain, and gynaecological conditions). Methods: Participants were aged 18 years or above and had an autism diagnosis recorded in the IQVIA Medical Research Database between 01/01/2000 and 16/01/2019. We included 15,675 autistic adults without intellectual disability, 6437 autistic adults with intellectual disability, and a comparison group matched (1:10) by age, sex, and primary care practice. We estimated crude incidences and incidence rate ratios (IRRs) adjusted for age and sex. Findings: Autistic adults without intellectual disability experienced a higher incidence (IRR, 95% CI) of self-harm (2.07, 1.79-2.40), anxiety (1.91, 1.76-2.06), depressive disorders (1.79, 1.67-1.92), and substance use (1.24, 1.02-1.51) relative to comparison participants. Incidences of harmful alcohol use (1.01, 0.85-1.18), migraine (0.99, 0.84-1.17), and gynaecological conditions (1.19, 0.95-1.49) did not differ. Neck or back pain incidence was lower (0.88, 0.82-0.95). Autistic adults with intellectual disability experienced a higher incidence of self-harm (2.08, 1.69-2.56). Incidences of anxiety (1.14, 1.00-1.30), gynaecological conditions (1.22, 0.93-1.62), and substance use (1.08, 0.80-1.47) did not differ, and lower incidences were found for depressive disorders (0.73, 0.64-0.83), harmful alcohol use (0.65, 0.50-0.84), migraine (0.55, 0.42-0.74), and neck or back pain (0.49, 0.44-0.55). Interpretation: Although our findings cannot be directly compared to previous prevalence studies, they contrast with the higher frequency of mental and physical health conditions in autistic adults reported in studies that directly assessed and/or surveyed autistic people about co-occurring conditions. The present findings may suggest under-diagnosis of common conditions in autistic people, particularly those with intellectual disability. Improved detection should be a clinical and policy priority to reduce health inequalities. Funding: Dunhill Medical Trust, Economic and Social Research Council, National Institute of Health and Care Research.
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Background: Previous research has shown that people who have been diagnosed autistic are more likely to die prematurely than the general population. However, statistics on premature mortality in autistic people have often been misinterpreted. In this study we aimed to estimate the life expectancy and years of life lost experienced by autistic people living in the UK. Methods: We studied people in the IQVIA Medical Research Database with an autism diagnosis between January 1, 1989 and January 16, 2019. For each participant diagnosed autistic, we included ten comparison participants without an autism diagnosis, matched by age, sex, and primary care practice. We calculated age- and sex-standardised mortality ratios comparing people diagnosed autistic to the reference group. We used Poisson regression to estimate age-specific mortality rates, and life tables to estimate life expectancy at age 18 and years of life lost. We analysed the data separately by sex, and for people with and without a record of intellectual disability. We discuss the findings in the light of the prevalence of recorded diagnosis of autism in primary care compared to community estimates. Findings: From a cohort of nearly 10 million people, we identified 17,130 participants diagnosed autistic without an intellectual disability (matched with 171,300 comparison participants), and 6450 participants diagnosed autistic with an intellectual disability (matched with 64,500 comparison participants). The apparent estimates indicated that people diagnosed with autism but not intellectual disability had 1.71 (95% CI: 1.39-2.11) times the mortality rate of people without these diagnoses. People diagnosed with autism and intellectual disability had 2.83 (95% CI: 2.33-3.43) times the mortality rate of people without these diagnoses. Likewise, the apparent reduction in life expectancy for people diagnosed with autism but not intellectual disability was 6.14 years (95% CI: 2.84-9.07) for men and 6.45 years (95% CI: 1.37-11.58 years) for women. The apparent reduction in life expectancy for people diagnosed with autism and intellectual disability was 7.28 years (95% CI: 3.78-10.27) for men and 14.59 years (95% CI: 9.45-19.02 years) for women. However, these findings are likely to be subject to exposure misclassification biases: very few autistic adults and older-adults have been diagnosed, meaning that we could only study a fraction of the total autistic population. Those who have been diagnosed may well be those with greater support needs and more co-occurring health conditions than autistic people on average. Interpretation: The findings indicate that there is a group of autistic people who experience premature mortality, which is of significant concern. There is an urgent need for investigation into the reasons behind this. However, our estimates suggest that the widely reported statistic that autistic people live 16-years less on average is likely incorrect. Nine out of 10 autistic people may have been undiagnosed across the time-period studied. Hence, the results of our study do not generalise to all autistic people. Diagnosed autistic adults, and particularly older adults, are likely those with greater-than-average support needs. Therefore, we may have over-estimated the reduction in life expectancy experienced by autistic people on average. The larger reduction in life expectancy for women diagnosed with autism and intellectual disability vs. men may in part reflect disproportionate underdiagnosis of autism and/or intellectual disability in women. Funding: Dunhill Medical Trust, Medical Research Council, National Institute for Health and Care Research, and the Royal College of Psychiatrists.
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BACKGROUND: Cognitive stimulation therapy (CST) is an evidence-based, group psychosocial intervention for people with dementia, and it has a positive impact on cognition and quality of life. CST has been culturally adapted for use globally. It was developed as a face-to-face intervention but has recently been adapted for online delivery. OBJECTIVE: In this study, we aimed to explore the feasibility and acceptability of online or virtual CST (vCST) delivery in India and Brazil, emphasizing barriers and facilitators to implementation. METHODS: A single-group, multisite, mixed methods, feasibility study was conducted, with nested qualitative interviews. Primary feasibility outcomes were recruitment rate, attendance, attrition, acceptability, and outcome measure completion. Exploratory pre- and postintervention measures, including cognition and quality of life, were assessed. Qualitative interviews were conducted with people with dementia, family caregivers, and group and organizational leaders following intervention delivery, and the data were analyzed using the Consolidated Framework for Implementation Research. RESULTS: A total of 17 vCST group sessions with 59 participants were conducted for 7 weeks, with 53% (31/59) of participants attending all 14 sessions. Attrition rate was 7% (4/59), and outcome measure completion rate at follow-up was 68% (40/59). Interviews took place with 36 stakeholders. vCST was acceptable to participants and group leaders and enabled vital access to services during pandemic restrictions. While online services broadened geographic access, challenges emerged concerning inadequate computer literacy, poor technology access, and establishing interpersonal connections online. Exploratory, uncontrolled analyses indicated positive trends in quality of life but negative trends in cognition and activities of daily living, but these results were not statistically significant. CONCLUSIONS: vCST demonstrated feasibility and acceptability, serving as a crucial resource during the pandemic but raised challenges related to technology access, computer literacy, and long-term implementation. The study highlights the potential of vCST while emphasizing ongoing development and solutions to address implementation challenges.
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Terapia Cognitivo-Comportamental , Demência , Estudos de Viabilidade , Qualidade de Vida , Humanos , Demência/terapia , Índia/epidemiologia , Brasil/epidemiologia , Feminino , Masculino , Idoso , Terapia Cognitivo-Comportamental/métodos , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Idoso de 80 Anos ou mais , Cuidadores/psicologiaRESUMO
BACKGROUND: Autistic adults report a higher prevalence of anxiety and depression than adults without identified autism but have poorer access to appropriate mental health care. Evidence-based psychological therapies are recommended in treatment guidelines for autistic adults, but no study has investigated their effectiveness in large samples representative of the autistic population accessing routine care. This study aimed to examine therapy outcomes for autistic adults in a primary care service. METHODS: In this retrospective, matched, observational cohort study of national health-care records, we used the MODIFY dataset that used linked electronic health-care records, including national data, for individuals who accessed psychological therapy in primary care in Improving Access to Psychological Therapies (IAPT) services in 211 clinical commissioning group areas in England, UK. All adults aged 18 years or older who had completed a course of IAPT in 2012-19 were eligible, and were propensity score matched (1:1) with a comparison group without identified autism. Exact matching was used, when possible, for a range of sociodemographic factors. Primary outcomes were routine metrics that have been nationally defined and used to evaluate IAPT treatments: reliable improvement, reliable recovery, and reliable deterioration. Secondary outcomes were calculated pre-post treatment changes in scores for Patient Health Questionnaire-9, Generalised Anxiety Disorder Assessment-7, and Work and Social Adjustment Scale measures. Subgroup analyses investigated differential effects across a range of sociodemographic factors. FINDINGS: Of 2â515â402 adults who completed at least two sessions of IAPT in 2012-19, 8761 had an autism diagnosis (5054 [57·7%] male and 3707 [42·3%] female) and 1â918â504 did not (631â606 [32·9%] male and 1â286â898 [67·0%] female). After propensity score matching, 8593 autistic individuals were matched with an individual in the comparison group. During IAPT treatment, symptoms of depression and generalised anxiety disorder decreased for most autistic adults, but symptoms were less likely to improve in the autism group than in the comparison group (4820 [56·1%] of 8593 autistic adults had reliable improvement vs 5304 [61·7%] of 8593 adults in the matched group; adjusted odds ratio [ORadj] 0·75, 95% CI 0·70-0·80; p<0·0001) and symptoms were more likely to deteriorate (792 [9·2%] vs 619 [7·2%]; ORadj 1·34, 1·18-1·48; p<0·0001). In the comparison group, improved outcomes were associated with employment and belonging to a higher socioeconomic deprivation category, but this was not the case for autistic adults. INTERPRETATION: Evidence-based psychological therapy for depression or anxiety might be effective for autistic adults but less so than for adults without identified autism. Treatment moderators appear different for autistic individuals, so more research is needed to allow for better targeted and personalised care. FUNDING: Alzheimer's Society.
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Transtorno Autístico , Terapia Cognitivo-Comportamental , Humanos , Adulto , Masculino , Feminino , Depressão/epidemiologia , Depressão/terapia , Estudos Retrospectivos , Resultado do Tratamento , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/terapia , Ansiedade/epidemiologia , Ansiedade/terapia , Inglaterra/epidemiologia , Estudos de Coortes , Atenção Primária à SaúdeRESUMO
INTRODUCTION: Ixekizumab, a selective interleukin-17A antagonist, was compared with adalimumab in the SPIRIT-H2H study (NCT03151551) in patients with psoriatic arthritis (PsA) and concomitant psoriasis. This post hoc analysis reports outcomes to week 52 in patients from SPIRIT-H2H, stratified by baseline psoriasis severity. METHODS: SPIRIT-H2H was a 52-week, multicenter, randomized, open-label, rater-blinded, parallel-group study of biologic disease-modifying antirheumatic drug (DMARD)-naïve patients (N = 566) with PsA and active psoriasis (≥ 3% body surface area involvement). Patients were randomized to ixekizumab or adalimumab (1:1) with stratification by baseline concomitant use of conventional synthetic DMARDs and psoriasis severity (with/without moderate-to-severe psoriasis). Patients received on-label dosing according to psoriasis severity. The primary endpoint was the proportion of patients simultaneously achieving ≥ 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100) at week 24. Secondary endpoints included musculoskeletal, disease activity (defined by composite indices), skin and nail, quality of life and safety outcomes. In this post hoc analysis, primary and secondary endpoints of SPIRIT-H2H were analyzed by baseline psoriasis severity. RESULTS: A greater proportion of patients achieved the combined endpoint of ACR50 + PASI100 and PASI100 with ixekizumab compared with adalimumab at weeks 24 and 52, regardless of baseline psoriasis severity. ACR response rates were similar for ixekizumab and adalimumab across both patient subgroups. For musculoskeletal outcomes, similar efficacy was seen for ixekizumab and adalimumab, but ixekizumab showed greater responses for skin outcomes regardless of psoriasis severity. The safety profiles of ixekizumab and adalimumab were consistent between subgroups. CONCLUSIONS: Regardless of baseline psoriasis severity, ixekizumab demonstrated greater efficacy than adalimumab with respect to simultaneous achievement of ACR50 + PASI100, and showed consistent and sustained efficacy across PsA-related domains. It also demonstrated higher response rates for skin outcomes. These subgroup analyses highlight the efficacy of ixekizumab in patients with PsA irrespective of the severity of concomitant psoriasis.
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PURPOSE: Understanding risk factors for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is important for optimizing patient care. We re-analyzed data from the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study (NCT00292552) to identify factors predictive of re-exacerbations and associated with prolonged AECOPDs. METHODS: Patients with COPD from ECLIPSE with moderate/severe AECOPDs were included. The end of the first exacerbation was the index date. Timing of re-exacerbation risk was assessed in patients with 180 days' post-index-date follow-up data. Factors predictive of early (1-90 days) vs late (91-180 days) vs no re-exacerbation were identified using a multivariable partial-proportional-odds-predictive model. Explanatory logistic-regression modeling identified factors associated with prolonged AECOPDs. RESULTS: Of the 1,554 eligible patients from ECLIPSE, 1,420 had 180 days' follow-up data: more patients experienced early (30.9%) than late (18.7%) re-exacerbations; 50.4% had no re-exacerbation within 180 days. Lower post-bronchodilator FEV1 (P=0.0019), a higher number of moderate/severe exacerbations on/before index date (P<0.0001), higher St. George's Respiratory Questionnaire total score (P=0.0036), and season of index exacerbation (autumn vs winter, P=0.00164) were identified as predictors of early (vs late/none) re-exacerbation risk within 180 days. Similarly, these were all predictors of any (vs none) re-exacerbation risk within 180 days. Median moderate/severe AECOPD duration was 12 days; 22.7% of patients experienced a prolonged AECOPD. The odds of experiencing a prolonged AECOPD were greater for severe vs moderate AECOPDs (adjusted odds ratio=1.917, P=0.002) and lower for spring vs winter AECOPDs (adjusted odds ratio=0.578, P=0.017). CONCLUSION: Prior exacerbation history, reduced lung function, poorer respiratory-related quality-of-life (greater disease burden), and season may help identify patients who will re-exacerbate within 90 days of an AECOPD. Severe AECOPDs and winter AECOPDs are likely to be prolonged and may require close monitoring.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Estudos de Coortes , Progressão da Doença , Humanos , Razão de Chances , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Índice de Gravidade de DoençaRESUMO
Background: Chronic cough and phlegm are frequently reported chronic obstructive pulmonary disease (COPD) symptoms. Prior research classified chronic mucus hypersecretion (CMH) based on the presence of these symptoms for ≥3 months, called chronic bronchitis (CB) if respiratory infection symptoms were present for 1-2 years (Medical Research Council [MRC] definition). We explored whether the COPD Assessment Test (CAT), a simple measure developed for routine clinical use, captures CMH populations and outcomes similarly to MRC and St. George's Respiratory Questionnaire (SGRQ) definitions. Methods: We identified CMH in the SPIROMICS COPD cohort using (a) MRC definitions, (b) SGRQ questions for cough and phlegm (both as most/several days a week), and (c) CAT cough and phlegm questions. We determined optimal cut-points for CAT items and described exacerbation frequencies for different CMH definitions. Moderate exacerbations required a new prescription for antibiotics/oral corticosteroids or emergency department visit; severe exacerbations required hospitalization. Results were stratified by smoking status. Results: In a population of 1431 participants (57% male; mean FEV1% predicted 61%), 47% and 49% of evaluable participants had SGRQ- or CAT-defined CMH, respectively. A cut-point of ≥2 for cough and phlegm items defined CMH in CAT. Among SGRQ-CMH+ participants, 80% were also defined as CMH+ by the CAT. CMH+ participants were more likely to be current smokers. A higher exacerbation frequency was observed for presence of CMH+ versus CMH- in the year prior to baseline for all CMH definitions; this trend continued across 3 years of follow-up, regardless of smoking status. Conclusion: Items from the CAT identified SGRQ-defined CMH, a frequent COPD trait that correlated with exacerbation frequency. The CAT is a short, simple questionnaire and a potentially valuable tool for telemedicine or real-world trials. CAT-based CMH is a novel approach for identifying clinically important characteristics in COPD that can be ascertained in these settings.