Drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis: a prospective cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR).

BACKGROUND: Real-world biologic drug survival is an important proxy measure for effectiveness. Predictors of drug survival may help patients with psoriasis choose between biologic therapies. OBJECTIVES: (i) To assess the relative drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis. (ii) To investigate predictors of biologic drug survival. METHODS: A prospective cohort study was performed in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2019. We performed survival analysis and fitted a flexible parametric survival model for biologic discontinuation due to ineffectiveness. RESULTS: In total 9652 patients were included: 5543 starting on adalimumab (57·4%), 991 on secukinumab (10·3%) and 3118 on ustekinumab (32·3%). The overall drug survivals of adalimumab, secukinumab and ustekinumab in year 1 were 0·78 [95% confidence interval (CI) 0·77-0·79], 0·88 (95% CI 0·86-0·91) and 0·88 (95% CI 0·87-0·89), respectively. The adjusted hazard ratios (adjHRs) for discontinuation of adalimumab and secukinumab compared with ustekinumab were 2·11 (95% CI 1·76-2·54) and 0·67 (95% CI 0·40-1·11), respectively. The presence of psoriatic arthritis predicted for survival in the adalimumab and secukinumab cohorts (adjHR 0·67, 95% CI 0·51-0·88 and 0·70, 95% CI 0·40-1·24, respectively), but for discontinuation in the ustekinumab cohort (adjHR 1·42, 95% CI 1·12-1·81). Previous exposure to biologic therapies predicted for discontinuation in the ustekinumab and secukinumab cohorts (adjHR 1·54, 95% CI 1·26-1·89 and 1·49, 95% CI 0·91-2·45, respectively) and for survival in the adalimumab cohort (adjHR 0·71, 95% CI 0·55-0·92). CONCLUSIONS: Secukinumab and ustekinumab have similar sustained drug survival, while adalimumab has a lower drug survival in patients with psoriasis. Psoriatic arthritis and previous biologic experience were predictors with differential effects between the biologic therapies. What is already known about this topic? There is conflicting evidence over the real-world drug survival of secukinumab in patients with psoriasis. Data from registries to date suggest that secukinumab has a lower drug survival than that reported from clinical trials. What does this study add? This study found that secukinumab and ustekinumab had similar sustained drug survival in the real world, while the drug survival of adalimumab was lower, suggesting that the real-world drug survival of secukinumab is higher than previously reported. We found that psoriatic arthritis and previous biologic experience had differential effects on drug discontinuation in the three biologic cohorts. These predictors may help patients and clinicians choose the most appropriate biologic therapy

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

Does message framing affect changes in behavioural intentions in people with psoriasis? A randomized exploratory study examining health risk communication

Message framing is important in health communication research to encourage behaviour change. Psoriasis, a long-term inflammatory skin condition, has additional comorbidities including high levels of anxiety and cardiovascular disease (CVD), making message framing particularly important. This experimental study aimed to: (1) identify whether health messages about psoriasis presented as either gain- or loss-framed were more effective for prompting changes in behavioural intentions (BI), (2) examine whether BI were driven by a desire to improve psoriasis or reduce CVD risk; (3) examine emotional reactions to message frame; and (4) examine predictors of BI. A two by two experiment examined the effects on BI of message frame (loss vs. gain) and message focus (psoriasis symptom reduction vs. CVD risk reduction). Participants with psoriasis (n = 217) were randomly allocated to one of four evidence-based health messages related to either smoking, alcohol, diet or physical activity, using an online questionnaire. BI was the primary outcome. Analysis of variance tests and hierarchical multiple regression analyses were conducted. A significant frame by focus interaction was found for BI to reduce alcohol intake (p = .023); loss-framed messages were more effective for CVD risk reduction information, whilst gain-framed messages were more effective for psoriasis symptom reduction information. Message framing effects were not found for BI for increased physical activity and improving diet. High CVD risk was a significant predictor of increased BI for both alcohol reduction (β = .290, p < .01) and increased physical activity (β = −.231, p < .001). Message framing may be an important factor to consider depending on the health benefit emphasised (disease symptom reduction or CVD risk reduction) and patient-stated priorities. Condition-specific health messages in psoriasis populations may increase the likelihood of message effectiveness for alcohol reduction

A standardization approach to compare treatment safety and effectiveness outcomes between clinical trials and real‐world populations in psoriasis

Background: Patients recruited in randomized controlled trials (RCTs) for biologic therapies in psoriasis are not fully representative of the real‐world psoriasis population. Objectives: Firstly, to investigate whether patient characteristics are associated with being included in a psoriasis RCT. Secondly, to estimate the differences in the incidence of severe adverse events (SAEs) and the response rate between RCT and real‐world populations of patients on biologic therapies for psoriasis using a standardization method. Methods: Data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) were appended to individual participant‐level data from two RCTs assessing ustekinumab in patients with psoriasis. Baseline variables were assessed for association of being in an RCT using a multivariable logistic regression model. Propensity score weights were derived to reweigh the registry population so that variables had the distribution of the trial population. We measured the C‐statistic of the model with trial status as the dependent variable, and the risk differences in the incidence rate of SAEs in the first year and Psoriasis Area and Severity Index (PASI) after 6 months in the BADBIR cohort before and after weighting. Results: In total 6790 registry and 2021 RCT participants were included. The multivariable logistic regression model had a C‐statistic of 0.82 [95% confidence interval (CI) 0.81–0.83]. The risk differences for the incidence rate of SAEs and the proportion of patients with PASI &lt; 1.5 were 9.27 (95% CI −3.91–22.5) per 1000 person‐years and 0.95 (95% CI −1.98–4.15), respectively. Conclusions: Our results suggest that RCTs of biologic therapies in patients with psoriasis are not fully representative of the real‐world population, but this lack of external validity does not account for the efficacy–effectiveness gap

The ICAM-3/LFA-1 interaction is critical for epidermal Langerhans cell alloantigen presentation to CD4 + T cells

Intercellular adhesion molecule (ICAM)-3 is a recently described member of the immunoglobulin superfamily and, as such, is closely related to ICAM-1 and ICAM-2. All three ICAMS are cognate for the counter-receptor lymphocyte function associated antigen-1 (LFA-L CD11a/CD18). Unlike ICAM-1 and ICAM-2. ICAM-3 is constitutively expressed at high levels on resting leucocytes. We investigated the expression and function of ICAM-3 in normal skin ( n = 5), as well as its expression in psoriasis ( n = 4). atopic eczema ( n = 4), allergic (rhus) contact dermatitis ( n =3). and cutaneous T-cell lymphoma (CTCL. n =2). Five-micrometre cryostat sections of skin were stained using monoclonal antibodies to ICAM-3 and A well characterized immunoperoxidase technique. In normal skin. ICAM-3 was expressed by all cutaneous leucocytes hut most striking was the strong expression of ICAM-3 by Langerhans cells within both epidermis and dermis. This observation was confirmed by double-labelling with CD1a and negative staining with an IgG1 isotype control. In psoriasis, atopic eczema, allergic contact dermatitis, and CTCL. ICAM-3 was co-expressed on all CD1a + cells, although, in psoriasis, the intensity of ICAM-3 expression was reduced. Functional blocking experiments were performed to determine whether the observed ICAM-3 expression on Langerhans cells was functionally important in antigen presentation. CD4 + T cells were prepared from peripheral blood and 10 5 CD4 + T cells combined with 10 5 epidermal cells harvested from keratome biopsies of normal skin of an individual allogeneic to the T-cell donor. Addition of 50 Μg anti-ICAM-3 to the co-culture resulted in a consistent (50%) reduction in degree of alloantigen presentation by Langerhans cells to T cells. Inhibition was 77% of that produced by the addition of anti-LFA-1. These data indicate that ICAM-3 is constitutively expressed by Langerhans cells and is a major ligand for LFA-1 on CD4 + T cells during their response to Langerhans cells. Because fresh Langerhans ceils constitutively express little ICAM-1. whereas ICAM-3 is constitutively expressed at high levels, it would appear that 1CAM-3 is the dominant functional ICAM on in situ Langerhans cells in the normal epidermis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73969/1/j.1365-2133.1995.tb06911.x.pd