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BackgroundPatients with psoriasis are often concerned about the risk of serious infection associated with systemic psoriasis treatments.ObjectivesTo develop and externally validate a prediction model for serious infection in patients with psoriasis within 1 year of starting systemic therapies.MethodsThe risk prediction model was developed using the British Association of Dermatologists Biologic Interventions Register (BADBIR), and the German Psoriasis Registry PsoBest was used as the validation dataset. Model discrimination and calibration were assessed internally and externally using the C‐statistic, the calibration slope and the calibration in the large.ResultsOverall 175 (1·7%) out of 10 033 participants from BADBIR and 41 (1·7%) out of 2423 participants from PsoBest developed a serious infection within 1 year of therapy initiation. Selected predictors in a multiple logistic regression model included nine baseline covariates, and starting infliximab was the strongest predictor. Evaluation of model performance showed a bootstrap optimism‐corrected C‐statistic of 0·64 [95% confidence interval (CI) 0·60–0·69], calibration in the large of 0·02 (95% CI −0·14 to 0·17) and a calibration slope of 0·88 (95% CI 0·70–1·07), while external validation performance was poor, with C‐statistic 0·52 (95% CI 0·42–0·62), calibration in the large 0·06 (95% CI −0·25 to 0·37) and calibration slope 0·36 (95% CI −0·24 to 0·97).ConclusionsWe present the first results of the development of a multivariable prediction model. This model may help patients and dermatologists in the U.K. and the Republic of Ireland to identify modifiable risk factors and inform therapy choice in a shared decision‐making process.

BackgroundPatients with psoriasis and clinicians are concerned that infliximab may be associated with a risk of serious infections.ObjectivesTo compare the risk of serious infections associated with infliximab in patients with chronic plaque psoriasis against a cohort on nonbiologic systemic therapies.MethodsA prospective cohort study was performed using data from the British Association of Dermatologists Biologic Interventions Register (BADBIR). Infliximab was compared with nonbiologic systemic therapies, inclusive of any exposure to methotrexate, ciclosporin, acitretin, fumaric acid esters, psoralen‐ultraviolet A or hydroxycarbamide. Serious infections were those associated with hospitalization, the use of intravenous antimicrobial therapy and/or those that led to death. Propensity score inverse probability treatment weights were used to adjust for potential confounding from a priori identified covariates. Cox proportional hazards models were calculated to obtain hazard ratios (HRs).ResultsIn total, 3843 participants were included for analysis up to October 2016. The incidence rates were significantly higher in the infliximab cohort (47·8 per 1000 person‐years) [95% confidence interval (CI) 35·7–64·0], compared with 14·2 per 1000 person‐years (95% CI 11·5–17·4) in the nonbiologic systemic cohort. Infliximab was associated with an overall increase in the risk of serious infection compared with nonbiologics [adjusted HR (adjHR) 1·95, 95% CI 1·01–3·75] and methotrexate only (adjHR 2·96, 95% CI 1·58–5·57) and a higher risk of serious infection in the first 6 months of therapy (adjHR 3·49, 95% CI 1·14–10·70).ConclusionsInfliximab is associated with an increased risk of serious infections compared with nonbiologic systemic therapies in patients with psoriasis in the U.K. and the Republic of Ireland.

SummaryBackgroundSince the mid-1990s, excess mortality has increased markedly for adults aged 25–44 years in the north compared with the south of England. We examined the underlying causes of this excess mortality and the contribution of socioeconomic deprivation.MethodsMortality data from the Office of National Statistics for adults aged 25–44 years were aggregated and compared between England's five most northern versus five most southern government office regions between Jan 1, 1981, and Dec 31, 2016. Poisson regression models, adjusted for age and sex, were used to quantify excess mortality in the north compared with the south by underlying cause of death (accidents, alcohol related, cardiovascular disease and diabetes, drug related, suicide, cancer, and other causes). The role of socioeconomic deprivation, as measured by the 2015 Index of Multiple Deprivation, in explaining the excess and regional variability was also explored.FindingsA mortality divide between the north and south appeared in the mid-1990s and rapidly expanded thereafter for deaths attributed to accidents, alcohol misuse, and drug misuse. In the 2014–16 period, the northern excess was incidence rate ratio (IRR) 1·47 (95% CI 1·39–1·54) for cardiovascular reasons, 2·09 (1·94–2·25) for alcohol misuse, and 1·60 (1·51–1·70) for drug misuse, across both men and women aged 25–44 years. National mortality rates for cardiovascular deaths declined over the study period but a longstanding gap between north and south persisted (from 33·3 [95% CI 31·8–34·8] in 1981 to 15·0 [14·0–15·9] in 2016 in the north vs from 23·5 [22·3–24·8] to 9·9 [9·2–10·5] in the south). Between 2014 and 2016, estimated excess numbers of death in the north versus the south for those aged 25–44 years were 1881 (95% CI 726–2627) for women and 3530 (2216–4511) for men. Socioeconomic deprivation explained up to two-thirds of the excess mortality in the north (IRR for northern effect reduced from 1·15 [95% CI 1·14–1·15; unadjusted] to 1·05 [1·04–1·05; adjusted for Index of Multiple Deprivation]). By 2016, in addition to the persistent north–south gap, mortality rates in London were lower than in all other regions, with IRRs ranging from IRR 1·13 (95% CI 1·12–1·15) for the East England to 1·22 (1·20–1·24) for the North East, even after adjusting for deprivation.InterpretationSharp relative rises in deaths from cardiovascular reasons, alcohol misuse and drug misuse in the north compared with the south seem to have created new health divisions between England's regions. This gap might be due to exacerbation of existing social and health inequalities that have been experienced for many years. These divisions might suggest increasing psychological distress, despair, and risk taking among young and middle-aged adults, particularly outside of London.FundingMedical Research Council and Wellcome Trust.

BACKGROUND: Patients with psoriasis and clinicians are concerned that infliximab may be associated with a risk of serious infections.OBJECTIVES: To compare the risk of serious infections associated with infliximab in patients with chronic plaque psoriasis against a cohort on non-biologic systemic therapies.METHODS: A prospective cohort study was performed using data from BADBIR. Infliximab was compared to non-biologic systemic therapies, inclusive of any exposure to methotrexate, ciclosporin, acitretin, fumaric acid esters, psoralen-ultraviolet A or hydroxycarbamide. Serious infections were those associated with hospitalisation; the use of intravenous antimicrobial therapy; and/or led to death. Propensity-score inverse probability treatment weights were used to adjust for potential confounding from a priori identified covariates. Cox proportional hazards models were calculated to obtain hazard ratios.RESULTS: 3843 participants were included for analysis up to October 2016. The incidence rates were significantly higher in the infliximab cohort (47.8 per 1000 person-years (95% confidence interval (CI) 35.7, 64.0) compared to 14.2 per 1000 person-years (95% CI 11.5, 17.4) in the non-biologic systemic cohort. Infliximab was associated with an overall increase in the risk of serious infection against non-biologics (adjusted hazard ratio (adjHR) 1.95, 95% CI 1.01, 3.75) and methotrexate only (adjHR 2.96, 95% CI 1.58, 5.57) and a higher risk of serious infection in the first 6 months of therapy (adjHR 3.49, 95% CI 1.14, 10.70).CONCLUSIONS: Infliximab is associated with an increased risk of serious infections compared with non-biologic systemic therapies in patients with psoriasis in the United Kingdom and the Republic of Ireland. This article is protected by copyright. All rights reserved.

BACKGROUND: The burden of psoriasis across many world regions is high and there is a recognised need to better understand the epidemiology of this common skin disorder.OBJECTIVES: To examine changes in the prevalence and incidence of psoriasis, and mortality rates over a 15 year period.METHODS: Cohort study involving analysis of longitudinal electronic health records between 1999 and 2013 using the UK Clinical Practice Research Datalink (CPRD).RESULTS: The prevalence of psoriasis increased steadily from 2.3% (2297 cases per 100,000) in 1999 to 2.8% (2815 per 100,000) in 2013, which does not appear to be attributable to changes in incidence rates. We observed peaks in age-bands characteristic of early (type I) and late-onset (type II) psoriasis, and changes in incidence and prevalence rates with increasing latitude in the UK. All-cause mortality rates for the general population and for patients with psoriasis have decreased over the last 15 years. However, the risk of all-cause mortality for psoriasis patients remains elevated compared to people without psoriasis (hazard ratio (HR) 1.21; 95% CI 1.13-1.3) and we found no significant change in this relative excess mortality gap over time.CONCLUSIONS: We found an increasing population living longer with psoriasis in the UK which has important implications for healthcare service delivery and for resource allocation. Importantly, early mortality in patients with psoriasis remains elevated compared to the general population and we found no evidence of change in this premature mortality gap. This article is protected by copyright. All rights reserved.

BACKGROUND: Medication non-adherence is known to limit the effectiveness of available therapies, however little is known specifically about medication adherence in people with psoriasis. Medicines self-management can feel onerous to those with dermatological conditions due to the nature of therapies prescribed and many individuals with psoriasis experience additional challenges such as physical and psychological comorbidities that place significant additional demands on individuals and may undermine adherence. Viewing non-adherence to medication as an outcome of limited personal coping resources and conflicting goals may help explain medication non-adherence OBJECTIVE: To explore individuals' perspectives of their psoriasis, medication and its management.METHODS: Twenty people with psoriasis were recruited from community samples in England and interviewed in-depth about their perceptions of their psoriasis, medication, and adherence to medication and self-management advice. Data were analysed using Framework Analysis.RESULTS: Participants reported that adhering to recommended treatment regimens conflicted with the management of the physical and psychological demands of living with psoriasis. Medication usage was viewed as a source of unresolved emotional distress and, for some, resulted in poor self-reported adherence which included medication overuse, underuse and rejection of prescribed therapies. Perceived lack of engagement by clinicians with participants' self-management difficulties was viewed as an additional source of stress and distress.CONCLUSIONS: Adhering to medication in psoriasis can be an additional source of considerable emotional distress. We interpreted some episodes of non-adherence to psoriasis medication as rational attempts by individuals to minimise distress and to gain control over their life. This article is protected by copyright. All rights reserved.

BACKGROUND: The British Association of Dermatologists Biologic Interventions Register (BADBIR) is a prospective, observational cohort designed to assess the long-term safety of biologic and conventional systemic therapies used for adults with moderate-severe psoriasis in the UK and Republic of Ireland. OBJECTIVES: To describe the demographics, disease severity and co-morbidities of psoriasis patients on enrolment into BADBIR, and to highlight differences in those commencing biologic compared to conventional systemic therapies. METHOD: Baseline data were collected from 151 Dermatology departments in the UK and Republic of Ireland. Descriptive analysis was conducted.RESULTS: As of August 2014, 8399 patients were registered with BADBIR; 5065(60%) received biologics of whom 52.8% received adalimumab, 24.6% etanercept, 18.7% ustekinumab and 3.9% infliximab. In the comparator cohort 44.1% received methotrexate, 23.1% ciclosporin, 18.0% acitretin and 7.6% fumaric acid esters. 4897(58%) were male. Patients on biologics had a higher mean (±SD) age and disease duration than patients on conventional systemic therapies (46.3±12.7vs.44.3±14.3 years; 23.0±12.6vs.19.0±13.4 years, respectively; p1 co-morbidity. The most frequent co-morbidities were obesity (42.1%), hypertension (25.7%), depression (22.1%) and psoriatic arthritis (17.1%). CONCLUSION: BADBIR is an invaluable resource to study the safety and effectiveness of both biologic and conventional systemic therapies. Understanding differences in baseline characteristics between cohorts is crucial in undertaking future pharmacovigilance studies. This article is protected by copyright. All rights reserved.