Association between inflammatory joint disease and severe or treatment-resistant depression: population-based cohort and case-control studies in Sweden.

OBJECTIVE: To investigate whether the association between depression and inflammatory joint disease (IJD; rheumatoid arthritis [RA], psoriatic arthritis [PsA], ankylosing spondylitis/spondyloarthropathies [AS], and juvenile idiopathic arthritis [JIA]) is affected by the severity or treatment-resistance of depression. METHOD: Parallel cohort studies and case-control studies among 600,404 patients with a depressive episode identified in Swedish nationwide administrative registers. Prospective and retrospective risk for IJD in patients with depression was compared to matched population comparators, and the same associations were investigated in severe or treatment-resistant depression. Analyses were adjusted for comorbidities and sociodemographic covariates. RESULTS: Patients with depression had an increased risk for later IJD compared to population comparators (adjusted hazard ratio (aHR) for any IJD 1.34 [95% CI 1.30-1.39]; for RA 1.27 [1.15-1.41]; PsA 1.45 [1.29-1.63]; AS 1.32 [1.15-1.52]). In case-control studies, patients with depression more frequently had a history of IJD compared to population controls (adjusted odds ratio (aOR) for any IJD 1.43 [1.37-1.50]; RA 1.39 [1.29-1.49]; PsA 1.59 [1.46-1.73]; AS 1.49 [1.36-1.64]; JIA 1.52 [1.35-1.71]). These associations were not significantly different for severe depression or TRD. CONCLUSION: IJD and depression are bidirectionally associated, but this association does not seem to be influenced by the severity or treatment resistance of depression.

Estrogen-modulating treatment among mid-life women and COVID-19 morbidity and mortality: a multiregister nationwide matched cohort study in Sweden.

BACKGROUND: It has been repeatedly shown that men infected by SARS-CoV-2 face a twofold higher likelihood of dying, being hospitalized or admitted to the intensive care unit compared to women, despite taking into account relevant confounders. It has been hypothesized that these discrepancies are related to sex steroid hormone differences with estrogens being negatively correlated with disease severity. The objective of this study was therefore to evaluate COVID-19-related mortality and morbidity among peri- and postmenopausal women in relation to estrogen-containing menopause hormonal treatments (MHT). METHODS: This is a national register-based matched cohort study performed in Sweden between January 1 to December 31, 2020. Study participants comprised women over the age of 53 years residing in Sweden. Exposure was defined as prescriptions of local estrogens, systemic estrogens with and without progestogens, progestogens alone, or tibolone. MHT users were then compared with a matched cohort of non-users. The primary outcome consisted of COVID-19 mortality, whereas the secondary outcomes included inpatient hospitalizations/outpatient visits and confirmed SARS-CoV-2 infection. Multivariable adjusted Cox regression-derived hazard ratios (HRs) were calculated. RESULTS: Use of systemic estrogens alone is associated with increased COVID-19 mortality among older women (aHR 4.73, 1.22 to 18.32), but the association is no longer significant when discontinuation of estrogen use is accounted for. An increased risk for COVID-19 infection is further observed for women using combined systemic estrogens and progestogens (aHR 1.06, 1.00 to 1.13) or tibolone (aHR 1.21, 1.01 to 1.45). Use of local estrogens is associated with an increased risk for COVID-19-related death (aHR 2.02,1.45 to 2.81) as well as for all secondary outcomes. CONCLUSIONS: Systemic or local use of estrogens does not decrease COVID-19 morbidity and mortality to premenopausal background levels. Excess risk for COVID-19 morbidity and mortality was noted among older women and those discontinuing systemic estrogens. Higher risk for death was also noted among women using local estrogens, for which non-causal mechanisms such as confounding by comorbidity or frailty seem to be the most plausible underlying explanations. TRIAL REGISTRATION DETAILS: Not applicable.

Methodology of the brodalumab assessment of hazards: a multicentre observational safety (BRAHMS) study.

INTRODUCTION: Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections. METHODS AND ANALYSIS: BRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed. ETHICS AND DISSEMINATION: The study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EUPAS30280.

Risk of Major Cardiovascular and Cerebrovascular Events in Users of Lisdexamfetamine and Other Medications for Attention-Deficit/Hyperactivity Disorder in Denmark and Sweden: A Population-Based Cohort Study.

INTRODUCTION: This study aimed to estimate risks of cardiovascular and cerebrovascular events in patients treated with lisdexamfetamine dimesylate (LDX) compared with patients previously treated with other attention-deficit/hyperactivity disorder (ADHD) medications (amphetamine, dexamphetamine, methylphenidate or atomoxetine). METHODS: This population-based cohort study used data from Danish and Swedish medical and administrative national registers. The LDX cohort included adult patients initiating LDX with at least 12 months' data preceding first LDX dispensing (index date). A random sample of patients treated with at least one non-LDX ADHD medication in the 6-24 months (but not less than 6 months) before index date (previous-users cohort) were matched to LDX users on age, sex, region and calendar year. The primary outcome, a composite of major adverse cardiovascular and cerebrovascular events (MACE), included first hospitalisation for acute myocardial infarction or stroke and out-of-hospital coronary heart disease or cerebrovascular disease death. Incidence rates (IRs) and IR ratios (IRRs) with 95% confidence intervals (CIs) of MACE were estimated using Poisson regression. RESULTS: From Denmark/Sweden, 5516/40,163 LDX users and 27,494/200,389 previous users were included. In Denmark, IRs of MACE/1000 person-years (95% CI) were similar for LDX (1.63 [0.85-3.14]) and previous users (1.61 [1.28-2.01]). In Sweden, IRs (95% CI) were 1.40 (1.09-1.79) in LDX users and 1.17 (1.00-1.38) in previous users. Adjusted MACE IRRs (95% CI) for LDX versus previous use were 1.01 (0.48-2.13) in Denmark, 1.13 (0.75-1.71) in Sweden, and 1.10 (0.77-1.58) in the pooled analysis. CONCLUSION: Our findings suggest little to no increased risk of cardiovascular and cerebrovascular events in patients treated with LDX compared with patients previously treated with other ADHD medications.

Health care utilisation in treatment-resistant depression: a Swedish population-based cohort study.

OBJECTIVE: To investigate the health care utilisation (HCU) among patients with treatment-resistant depression (TRD) compared to patients with depression not meeting TRD criteria. METHODS: Nationwide Swedish registers were used to identify patients 18-69 years old with incident depression and antidepressant treatment. Patients were followed prospectively and defined as having TRD at start of the third distinct consecutive treatment episode. Each of the 16,329 identified TRD patients were matched with five comparators with depression not meeting criteria for TRD. Main outcome measure was total number of inpatient days and outpatient visits, and secondary outcome was HCU in connection with a main diagnosis of depression or suicide attempt. RESULTS: TRD patients had a significantly higher risk of all-cause inpatient care than comparators (first year adjusted risk ratio [aRR] 3.03 [95%CI 3.01-3.05], years 1-3 aRR 2.15 [2.13-2.16]). This was more pronounced when the main diagnosis was depression (first year aRR 4.41 [4.36-4.45]), and after suicide attempt (first year aRR 4.43 [4.26-4.60]). Outpatient visits were also markedly more frequent for patients with TRD (first year aRR 2.05 [2.03-2.07]). Higher HCU among TRD patients persisted throughout follow-up. CONCLUSIONS: Patients with TRD may have a twofold to fourfold higher HCU than other patients with depression.KEYPOINTSThis register-based prospective study investigated health care utilisation (HCU) among patients with treatment-resistant depression (TRD) compared to other patients with depression.Patients with TRD had a two to fourfold higher HCU regarding all measured outcomes, including inpatient hospital days and outpatient visits.The elevated HCU persisted for more than three years, although decreasing gradually. This should correspond to increased costs and individual burden for patients with TRD.

Societal impact for patients with psoriasis: A nationwide Swedish register study.

BACKGROUND: Psoriasis is an immune-mediated chronic inflammatory disease having a significant negative health impact. Psoriasis has societal impact; loss of productivity has been estimated at approximately 10% and it may influence the patient's financial status. Relationships between quality of life, disease severity, and cost of care need exploration. Understanding the disease burden is important for health policy and research allocation. Few studies address the research gaps in socioeconomics, comorbidity, and medication use. OBJECTIVE: Observing differences in education, income, employment status, marital status, health care consumption, and drug utilization between patients with psoriasis and matched controls. METHODS: Cohort study following socioeconomics and health care consumption for all psoriasis patients from the Swedish patient register. All individuals with a first diagnosis of psoriasis in outpatient or inpatient care from 2002 to 2013 were followed until death, emigration, or end of the study. RESULTS: Overall, 109,803 patients were included (mean age 51.2 years, 53% women) and matched with 1.08 million controls. The levels of education and income were similar, but the proportion employed was significantly lower for patients with psoriasis. There was a tendency for fewer patients with psoriasis to be married. LIMITATIONS: Generalizability, lack of primary care diagnoses, and lack of early treatments (available from 2005). CONCLUSION: Understanding of the socioeconomic impact of psoriasis is extended by showing reductions in employment.

The Occurrence of Metabolic Risk Factors Stratified by Psoriasis Severity: A Swedish Population-Based Matched Cohort Study.

PURPOSE: To assess the relative risk of metabolic risk factors in patients stratified by psoriasis severity compared with population controls. PATIENTS AND METHODS: A retrospective cohort study was conducted using national Swedish registers. Adult patients with psoriasis were selected if they had a dispensing of anti-psoriasis prescription (2007-2013) and at least one diagnosis within five years before the dispensing date. The patients with psoriasis were matched 1:10 to controls from the general population on birth year, sex, and county. The cohort was further divided into three disease severity groups (mild, moderate, or severe) based on their dispensed anti-psoriasis medication. Subjects were followed from the index date until censoring. We applied flexible parametric modeling to understand the risks of the incident comorbidities hypertension, hypercholesterolemia, and diabetes mellitus among patients with psoriasis from 6 months through 10 years. Hazard ratios and predicted risk (ie, 1 minus the survival probability) of comorbidities were reported. RESULTS: The hazard of hypertension, hypercholesterolemia, and diabetes mellitus is higher among psoriasis patients compared with population controls, and the hazard ratio increases with psoriasis severity. For example, HRs of hypertension for patients with mild, moderate, and severe psoriasis are 1.29 (95% CI: 1.27-1.32), 1.35 (95% CI: 1.32-1.38), and 1.73 (95% CI: 1.64-1.82), respectively. The predicted risk of hypertension, hypercholesterolemia, and diabetes mellitus among patients with severe psoriasis at year ten was 0.58 (95% CI: 0.56, 0.59), 0.33 (95% CI: 0.32, 0.35), and 0.21 (95% CI: 0.20, 0.23), respectively, while it was 0.42 (0.41, 0.43), 0.23 (0.22, 0.23), 0.11 (0.10, 0.11) among controls, respectively. The predicted risk at year ten was similar among patients with mild or moderate psoriasis. CONCLUSION: The HRs and predicted risks of metabolic risk factors are higher among patients with psoriasis compared with matched controls and are more prominent among the severe psoriasis group.

A register-based approach to identifying treatment-resistant depression-Comparison with clinical definitions.

BACKGROUND: Several definitions of treatment-resistant depression (TRD) are used for clinical research, but no verified model for use in register data exists. We aimed to compare a novel model created for use in register data-the Karolinska Institutet Model (KIM)-to the clinical definitions regarding the proportion of patients identified with TRD, their characteristics and clinical outcomes. METHODS: All patients in Sweden initiating antidepressant treatment with a diagnosis of depression in specialized healthcare 2006-2014 were identified and followed in national registers. In KIM, patients who initiated a third sequential, >28-day antidepressant treatment trial were defined as having TRD. Proportion of TRD and patient characteristics were compared with register adaptations of the European Staging Model (ESM), Massachusetts General Hospital Staging Method (MGH-s), and Maudsley Staging Model (MSM). Differences in patient characteristics were assessed with Chi-square tests and one-way ANOVAs. Hazard ratios for psychiatric hospitalization and for death from external causes were estimated by Cox proportional hazard regressions. RESULTS: Out of 127,108 antidepressant initiators with depression, the highest proportion of TRD was found using the MGH-s (19.0%), followed by MSM (15.3%), KIM (12.9%), and ESM (9.5%). Clinical characteristics were similar across the models. Compared with TRD patients identified by KIM, those identified by ESM had a marginally higher risk for psychiatric hospitalization (adjusted hazard ratio [aHR] 1.03, 95%CI 1.00-1.05), whereas those identified by MGH-s (aHR 0.92; 0.90-0.94) and MSM (aHR 0.95; 0.94-0.97) had a slightly reduced risk. Patients identified by MGH-s showed a reduced mortality compared with KIM (aHR 0.84; 0.72-0.98). CONCLUSIONS: This study provides insight into the differing characteristics of patients captured by various TRD models when used for register research. Models yielding lower proportions of TRD seemed to identify patients with greater morbidity. The KIM may be useful for register based research in TRD.

Risk of Acute Liver Injury in Agomelatine and Other Antidepressant Users in Four European Countries: A Cohort and Nested Case-Control Study Using Automated Health Data Sources.

BACKGROUND: Agomelatine is a melatonin receptor agonist and serotonin 5-HT2C receptor antagonist indicated for depression in adults. Hepatotoxic reactions like acute liver injury (ALI) are an identified risk in the European risk management plan for agomelatine. Hepatotoxic reactions have been reported for other antidepressants, but population studies quantifying these risks are scarce. Antidepressants are widely prescribed, and users often have risk factors for ALI (e.g. metabolic syndrome). OBJECTIVE: The goal was to estimate the risk of ALI associated with agomelatine and other antidepressants (fluoxetine, paroxetine, sertraline, escitalopram, mirtazapine, venlafaxine, duloxetine, and amitriptyline) when compared with citalopram in routine clinical practice. METHOD: A nested case-control study was conducted using data sources in Denmark, Germany, Spain, and Sweden (study period 2009-2014). Three ALI endpoints were defined using International Classification of Diseases (ICD) codes: primary (specific codes) and secondary (all codes) endpoints used only hospital discharge codes; the tertiary endpoint included both inpatient and outpatient settings (all codes). Validation of endpoints was implemented. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for current use were estimated for each data source and combined. RESULTS: We evaluated 3,238,495 new antidepressant and 74,440 agomelatine users. For the primary endpoint, the OR for agomelatine versus citalopram was 0.48 (CI 0.13-1.71). Results were also < 1 when no exclusion criteria were applied (OR 0.37; CI 0.19-0.74), when all exclusion criteria except alcohol and drug abuse were applied (OR 0.47; CI 0.20-1.07), and for the secondary (OR 0.40; CI 0.05-3.11) and tertiary (OR 0.79; CI 0.50-1.25) endpoints. Regarding other antidepressants versus citalopram, most OR point estimates were also below one, although with varying widths of the 95% CIs. The result of the tertiary endpoint and the sensitivity analyses of the primary endpoint were the most precise. CONCLUSION: In this study, using citalopram as a comparator, agomelatine was not associated with an increased risk of ALI hospitalisation. The results for agomelatine should be interpreted in the context of the European risk minimisation measures in place. Those measures may have induced selective prescribing and could explain the lower risk of ALI for agomelatine when compared with citalopram. Most other antidepressants evaluated had ORs suggesting a lower risk than citalopram, but additional studies are required to confirm or refute these results.

Antidepressant use in Denmark, Germany, Spain, and Sweden between 2009 and 2014: Incidence and comorbidities of antidepressant initiators.

BACKGROUND: We aimed to describe patterns of use and characteristics of 10 commonly used antidepressants for the period 2009-2014 in Denmark, Germany, Spain, and Sweden. METHODS: Adult initiators from 2009 to 2014 of each study antidepressant were identified in four countries using five data sources: the Danish National registers, GePaRD (Germany), EpiChron (Aragon, Spain), SIDIAP (Catalonia, Spain), and the Swedish National Registers. The study included 10 study antidepressants: citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, mirtazapine, and agomelatine. RESULTS: Citalopram was the most prescribed study antidepressant, followed by mirtazapine. Paroxetine and agomelatine were the least prescribed antidepressants. Mirtazapine was widely used among older antidepressant initiators with higher percentages of comorbidities at baseline, and fluoxetine was used among young patients. Citalopram and amitriptyline had the lowest percentage of multiple antidepressant use in the 12 months prior to the current treatment episode, while agomelatine, duloxetine, and venlafaxine had the highest percentage of multiple antidepressant use in the year prior to the current treatment episode. LIMITATIONS: The most important limitations are exposure information based on filled prescriptions, focus on antidepressant initiators only, lack of information on the indication, and heterogeneity of the type of data across data sources. CONCLUSIONS: Results of this study including 4.8 million study antidepressant initiators of study antidepressants suggest that citalopram and mirtazapine are the most commonly prescribed antidepressants. Agomelatine and paroxetine were the least used antidepressants in the participating populations. Mirtazapine was the antidepressant most commonly prescribed among older antidepressant initiators with high percentage of comorbidities at baseline, whereas fluoxetine was commonly used among young patients.

Mortality in treatment-resistant unipolar depression: A register-based cohort study in Sweden.

BACKGROUND: The impact of treatment resistant depression (TRD) on mortality is not established. METHODS: Using Swedish national registers, 118,774 patients between 18-69 years of age who had been prescribed an antidepressant and been diagnosed with depression in specialized care were identified. Patients with at least two additional treatment trials during the same depressive episode were classified as having TRD. Data on the covariates of sex, age, history of depression, self-harm, substance use disorders, and other psychiatric and somatic comorbidities was also used. Relative risks comparing TRD patients with other depressed patients were calculated as hazard ratios (HR) for all-cause mortality and for external and non-external causes of death, as well as excess mortality rate ratios (EMRR), with 95% confidence intervals (CI). RESULTS: In total 15,013 patients (13%) were classified with TRD. Adjusted HR for all-cause mortality was 1.35 (95% CI 1.21-1.50). Mortality from external causes (including suicides and accidents) was markedly higher in TRD patients than in other depressed patients (HR 1.97; 1.69-2.29), while mortality from non-external causes was similar. The adjusted EMRR was 1.52 (1.31-1.76), highest among patients 18-29 years old (EMRR 2.03; 1.31-1.76) and patients without somatic comorbidity (EMRR 1.99; 1.63-2.43). LIMITATIONS: Severity of depression and adherence to treatment were not available in the data. CONCLUSIONS: Patients with TRD may have an increased all-cause mortality compared to other depressed patients, mainly for external causes of death. The relative mortality is highest among young and physically healthy patients.

Young patients with risk factors prevalent in the elderly - differences in comorbidity depending on severity of psoriasis: a nationwide cross-sectional study in Swedish health registers.

BACKGROUND: Association between psoriasis severity and cerebro- and cardiovascular comorbidities has rarely been investigated. AIM: We aimed to investigate differences in cerebro- and cardiovascular comorbidities by psoriasis severity. MATERIALS AND METHODS: Using Swedish nationwide health-care registers, new adult users of anti-psoriatic drugs (2007-2013) with a recorded diagnosis of psoriasis/psoriatic arthritis or a filled prescription for calcipotriol were included. Psoriasis severity was based on the type of anti-psoriatic treatment (topical/mild, non-biologic systemic/moderate-to-severe, and biologics/ severe). Age standardized prevalence rates of cerebro- and cardiovascular comorbidities and their risk factors were compared between the groups. RESULTS: We found that severe psoriasis patients (N=2147) were younger than moderate-to-severe (N=11,919) or mild (N=70,796) patients (median 44, 52, and 55 years). Prevalence of hypertension was 29.9%, 32.6%, and 36.5%, myocardial infarction was 2.5%, 2.3%, and 1.8%, and stroke was 2.4%, 2.2%, and 1.1% in mild, moderate-to-severe, and severe psoriasis patients, respectively. Diabetes prevalence was 7.6% in mild, 8.0% in moderate-to-severe, and 10.7% in severe psoriasis. CONCLUSION: Myocardial infarction and stroke were less common in patients with severe psoriasis while, despite being younger, they had a higher prevalence of diabetes and hypertension.

Severity of Psoriasis Differs Between Men and Women: A Study of the Clinical Outcome Measure Psoriasis Area and Severity Index (PASI) in 5438 Swedish Register Patients.

BACKGROUND: Psoriasis is a common skin disease and moderate to severe psoriasis is associated with a dose-dependent risk for metabolic and cardiovascular morbidity. It has previously been speculated that women have less severe psoriasis, as men are overrepresented in psoriasis registers and consume more care. OBJECTIVE: The objective of this study was to investigate, for the first time, the sex differences in the severity of psoriasis using the gold standard of severity measurement, the Psoriasis Area and Severity Index (PASI), and the distinct elements of the PASI score. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional study based on the national registry for systemic treatment of psoriasis in Sweden (PsoReg), with 5438 patients experiencing moderate to severe psoriasis. Differences in the PASI score and its elements at enrolment were tested by multivariable ordinal logistic regressions. MAIN OUTCOME MEASURES: The different components of the PASI score were used to analyze the assessment of disease severity. For each body area (head, arms, trunk, and legs), the score of the plaque characteristics and degree of skin involvement were used as outcomes. RESULTS: Women had statistically significantly lower median PASI scores (5.4) than men (7.3) [p < 0.001], which was consistent across all ages. The difference remained statistically significant in a multivariable linear regression. The itemized PASI analyses from the Mann-Whitney-Wilcoxon tests and the adjusted ordinal logistic regressions confirmed that women had significantly lower scores than men in all areas of the body, except for the head. No differences in the use of medications prior to enrolment could be found that may cause this difference between the sexes. CONCLUSIONS: As the PsoReg contains the detailed disease measurement PASI, which was traditionally used for selected participants in clinical studies only, a nationwide unselected population could be investigated. The fact that women have less severe psoriasis can explain the dominance of males in the systemic treatment of psoriasis. These findings motivate a gender perspective in the management of psoriasis and in the prevention and management of its comorbidities.

The higher proportion of men with psoriasis treated with biologics may be explained by more severe disease in men.

OBJECTIVES: Moderate to severe psoriasis, once regarded as merely a skin disease, is today seen as an inflammatory systemic disease. The sex ratio of the prevalence of psoriasis is balanced. In recent years several reports have documented that men receive more systemic or UV treatment than women, and different hypotheses were made. In PsoReg, the national registry for systemic treatment of psoriasis in Sweden, we have, like other European registries, observed a predominance of men (59%), especially of men treated with biologics (63%). Biologics are a relatively new group of very effective but high-priced drugs. The objective of this study was to analyse if women are discriminated by not having the same access to the high-priced biologics. DESIGN: Population based cohort study using data from a nationwide quality register of psoriasis patients. POPULATION: 2294 patients with moderate to severe psoriasis receiving systemic treatment from a specialist in dermatology. MAIN OUTCOME MEASURES: Time to initiation of biologic treatment. A multiple Cox proportional hazard's regression was performed, with time to initiating a biologic treatment as the outcome in order to assess the independent role of the patient's sex in initiating such therapy. The psoriasis severity was defined as a time-varying variable. RESULTS: Men had more severe psoriasis than women according to the Psoriasis Area and Severity Index (PASI), regardless of age at enrolment, and throughout the study period. The analysis in the multiple Cox regression show that age, psoriasis severity and psoriasis arthropathy were relevant factors for initiating biologic therapy, whereas sex is not. CONCLUSIONS: Although as many women as men are believed to suffer from psoriasis, men seem to be more severely affected by psoriasis. The asymmetry in allocation of biologic therapy thereby probably reflects the differing disease activity between the sexes, and is not a discrimination against women per se.