Risk of major cardiovascular events in patients with psoriasis receiving biologic therapies: a prospective cohort study.

BACKGROUND: The cardiovascular safety profile of biologic therapies used for psoriasis is unclear. OBJECTIVES: To compare the risk of major cardiovascular events (CVEs; acute coronary syndrome, unstable angina, myocardial infarction and stroke) in patients with chronic plaque psoriasis treated with adalimumab, etanercept or ustekinumab in a large prospective cohort. METHODS: Prospective cohort study examining the comparative risk of major CVEs was conducted using the British Association of Dermatologists Biologics and Immunomodulators Register. The main analysis compared adults with chronic plaque psoriasis receiving ustekinumab with tumour necrosis-α inhibitors (TNFi: etanercept and adalimumab), whilst the secondary analyses compared ustekinumab, etanercept or methotrexate against adalimumab. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using overlap weights by propensity score to balance baseline covariates among comparison groups. RESULTS: We included 5468 biologic-naïve patients subsequently exposed (951 ustekinumab; 1313 etanercept; and 3204 adalimumab) in the main analysis. The secondary analyses also included 2189 patients receiving methotrexate. The median (p25-p75) follow-up times for patients using ustekinumab, TNFi, adalimumab, etanercept and methotrexate were as follows: 2.01 (1.16-3.21), 1.93 (1.05-3.34), 1.94 (1.09-3.32), 1.92 (0.93-3.45) and 1.43 (0.84-2.53) years, respectively. Ustekinumab, TNFi, adalimumab, etanercept and methotrexate groups had 7, 29, 23, 6 and 9 patients experiencing major CVEs, respectively. No differences in the risk of major CVEs were observed between biologic therapies [adjusted HR for ustekinumab vs. TNFi: 0.96 (95% CI 0.41-2.22); ustekinumab vs. adalimumab: 0.81 (0.30-2.17); etanercept vs. adalimumab: 0.81 (0.28-2.30)] and methotrexate against adalimumab [1.05 (0.34-3.28)]. CONCLUSIONS: In this large prospective cohort study, we found no significant differences in the risk of major CVEs between three different biologic therapies and methotrexate. Additional studies, with longer term follow-up, are needed to investigate the potential effects of biologic therapies on incidence of major CVEs.

Comparative effectiveness of biological therapies on improvements in quality of life in patients with psoriasis.

BACKGROUND: Evidence of the comparative effectiveness of biological therapies for psoriasis on health-related quality of life (HRQoL) in routine clinical practice is limited. OBJECTIVES: To examine the comparative effectiveness of adalimumab, etanercept and ustekinumab on HRQoL in patients with psoriasis, and to identify potential predictors for improved HRQoL. METHODS: This was a prospective cohort study in which changes in HRQoL were assessed using the Dermatology Life Quality Index (DLQI) and EuroQoL-5D (EQ-5D) at 6 and 12 months. Multivariable regression models were developed to identify factors associated with achieving a DLQI of 0/1 and improvements in the EQ-5D utility score. RESULTS: In total, 2152 patients with psoriasis were included, with 1239 patients on adalimumab, 517 on etanercept and 396 on ustekinumab; 81% were biologic naïve. For the entire cohort, the median (interquartile range) DLQI and EQ-5D improved from 18 (13-24) and 0·73 (0·69-0·80) at baseline to 2 (0-7) and 0·85 (0·69-1·00) at 6 months, respectively (P < 0·001). Similar improvements were achieved at 12 months. At 12 months, multivariable regression modelling showed that female sex, multiple comorbidities, smoking and a higher DLQI or a lower EQ-5D utility score at baseline predicted a lower likelihood of achieving a DLQI of 0/1 or improvement in the EQ-5D. Compared with adalimumab, patients receiving etanercept, but not ustekinumab, were less likely to achieve a DLQI of 0/1. There was no significant difference between the biological therapies in EQ-5D improvement. CONCLUSIONS: In routine clinical practice biological therapies produce marked improvement in HRQoL, which is influenced by the choice of biological therapy, baseline impairment in HRQoL, lifestyle characteristics and comorbidities. These findings should help inform selection of optimal biological therapy for patients related to improvements in HRQoL.

Identification of factors that may influence the selection of first-line biological therapy for people with psoriasis: a prospective, multicentre cohort study.

BACKGROUND: The Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium has a collective aim to develop a prescribing algorithm to help stratify eligible patients with psoriasis to the most appropriate biological treatment. To facilitate the adoption of a stratified approach, it is necessary to first understand the factors driving the choice of first-line biological therapy. OBJECTIVES: To identify and quantify factors that influence the selection of the first-line biological therapy for people with psoriasis. METHODS: Multinomial logistic regression was used to determine the factors that influenced the probability of treatment selection, using data from the British Association of Dermatologists Biologic Interventions Register from January 2012 to December 2015. Sensitivity analyses were performed to assess the robustness of the findings to key assumptions. RESULTS: The main analysis was based on a dataset comprising 3040 people with psoriasis. The identified factors affecting first-line biological selection within the available therapies were: presence of psoriatic arthritis; patient weight; employment status; country of registration; and baseline disease severity. Importantly, the analysis showed a general shift in prescribing behaviour over time. These results were robust to sensitivity analysis. CONCLUSIONS: This study offers important insights into the factors influencing current prescribing practice for first-line biological therapies for people with psoriasis. It provides baseline data to inform the evaluation of future potential changes that may affect prescribing behaviour, such as stratified medicine.

Patterns of biologic therapy use in the management of psoriasis: cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

BACKGROUND: Treatment modifications, including dose escalations, dose reductions, switches, discontinuations and restarts of biologics may be necessary in the management of psoriasis but the patterns of usage are incompletely defined. OBJECTIVES: To examine the treatment utilization patterns of adalimumab, etanercept and ustekinumab among biologic-naïve and non-naïve patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register (BADBIR). METHODS: The study cohort included adults with chronic plaque psoriasis who were followed up for ≥ 12 months. Treatment modifications were assessed during the first year of therapy. The time-trend method, comparing the cumulative dose (CD) patients received with the recommended cumulative dose (RCD), was used to assess dosing patterns. Concomitant use of other systemic treatments was also examined. RESULTS: In total, 2980 patients (adalimumab: 1675; etanercept: 996; ustekinumab: 309) were included; 79·2% were biologic-naïve. Over 12 months, 77·4% of patients continued the biologic, 2·6% restarted therapy after a break of ≥ 90 days, 2·5% discontinued, and 17·5% switched biologic therapy. Most patients (85·7%) received the RCD of the biologic, although 8·1% were exposed to a higher CD. In total, 749 (25·1%) patients used conventional systemic therapies concomitantly with a biologic at some stage; methotrexate was used most commonly (458; 61·2%). Of those using combination therapy, 454 (60·6%) continued the use of the conventional systemic therapy for > 120 days after the start of the biologic. CONCLUSIONS: More than one-third of patients experienced treatment modifications within the first year of initiating a biologic. Conventional systemic therapies, particularly methotrexate, were commonly used concurrently, which should be considered when evaluating treatment response and adverse events to biologics in real-world observational studies.

Successful treatment of psoriasis improves psoriasis-specific but not more general aspects of patients' well-being.

BACKGROUND: Psoriasis has a detrimental effect on patients' quality of life. However, there is a relative dearth of information on which aspects of a patient's well-being are affected by successful treatment. OBJECTIVES: To investigate whether, and to what extent, improvement in the clinical severity of psoriasis induced by photochemotherapy with psoralen plus ultraviolet A (PUVA) translates into meaningful changes in beliefs about psoriasis, coping, stress, distress or disability. METHODS: In a prospective study, 72 patients were assessed before PUVA therapy and again when they had achieved clearance of their psoriasis. RESULTS: Patients demonstrated significant reductions in psoriasis-related disability, psoriasis-related stress or daily hassles and in the frequency of psoriasis-related symptoms. By comparison, there were no significant differences in levels of anxiety, depression or worrying. Similarly, patients' perceptions about cure, potential chronicity, causes, consequences and coping also remained unchanged. CONCLUSIONS: These results suggest that while clearance of psoriasis produces a significant reduction in factors specific to psoriasis (disability and stress), it does not impact upon psychological distress, on patients' beliefs about psoriasis or on coping. This observation highlights the complex features of patients' psychological experience of psoriasis and may provide further impetus for integration of psychological interventions into standard care protocols.