Abstract
Objectives: This study evaluated self-reported patient adherence to different types of treatment in psoriasis and factors that affect adherence. Patients and methods: Patients attending a ...Dermatology Department for treatments of psoriasis completed a questionnaire about adherence to each of their therapies, Self-assessed Psoriasis Area and Severity Index (SAPASI) and Dermatology Life Quality Index (DLQI). Results: Hundred and six patients participated, 98 on topical treatments, 43 on oral systemic therapies, 39 on phototherapy and 29 were on biologic therapies. The overall rate of self-reported treatment adherence was 85.8%. There was a significant relationship between the types of treatment (topical, oral systemic, phototherapy and biologic therapy) and the number of combinations of treatments and adherence. Adherence ranked significantly better on biologic therapies 100%, followed by oral therapy 96%, phototherapy 93% and then topical therapy 75%. Being too busy, being fed up and cigarette smoking were associated with reduced adherence. About 56.8% of patients reported that messiness of treatment prevented them from adhering. Patients with mild psoriasis and those with DLQI of 5 or less adhered less to topical therapy. Conclusions: There is a significant relationship between the types of treatment (topical, oral systemic, phototherapy and biologic therapy) and the number of combinations of treatments and adherence.
Malignant melanoma is an aggressive form of cancer, which can be treated with anti-CTLA-4 and anti-PD-1 checkpoint inhibitor antibodies but while anti-CTLA-4 antibodies have clear benefits for some ...patients with melanoma, productive responses are difficult to predict and often associated with serious immune related adverse events. Antibodies specific to CTLA-4 bind two major isoforms of CTLA-4 in humans, the receptor isoform and a second naturally secretable, soluble isoform - sCTLA-4. The primary aim here was to examine the effect of selectively blocking the function of sCTLA-4 on
immune responses from volunteer healthy or melanoma patient PBMC samples. Addition of recombinant sCTLA-4 to healthy PBMC samples demonstrated sCTLA-4 to have immunosuppressive capacity comparable to recombinant CTLA4-Ig, partially reversible upon antibody blockade. Further, we identified a mechanistic relationship where melanoma patient TGFβ2 serum levels correlated with sCTLA-4 levels and provided the basis for a novel protocol to enhance sCTLA-4 production and secretion by T cells with TGFβ2. Finally, a comparison of selective antibody blockade of sCTLA-4 demonstrated that both healthy and melanoma patient effector cytokine responses can be significantly increased. Overall, the data support the notion that sCTLA-4 is a contributory factor in cancer immune evasion.
Examining the other side of the textbook image of the role of the early 20th century press as "crusader," this book presents a policy history of government regulation of the print media's business ...practices in the early 20th century. The first part of the book documents the press's inner workings,including its excesses and abuses, as it evolved from a collection of small businesses in the mid-1800s to an established commercial institution of the twentieth century. The second part of the book examines the regulatory actions brought about by publishers' fierce competition for advertisers and readers. In analyzing what this episode in policy making reveals about Progressive ideology's reliance on publicity and regulation to solve social and economic problems, the book integrates many of the apparently paradoxical strands of scholarship on the Progressive period. Chapters in the book are: (1) Introduction; (2) Hidden Ownership; (3) Disguised Advertisements; (4) Circulation Liars; (5) The Press Examined; (6) Ownership Disclosed; (7) Advertisements Identified; (8) Circulation Revealed; (9) Publicity as an Antidote for Press Abuses. A selected bibliography of books, journal articles, special archival collections, trade journal and newspapers, and government documents is attached. (RS)
Background:
Healthcare organizations need to attract and retain qualified nurses, and break areas may influence nurse engagement with breaks, but this has not been studied in situ. The goal of this ...study was to understand nurse perception of breaks and ways building design and culture impact the frequency, duration, and location of nurse breaks.
Methods:
This was Part 1 of a two-part study. Mixed-method approaches included on-site behavior mapping, focus groups, online survey, and break room usage rates analysis.
Findings:
In this study, nurses did not take restorative breaks but focused on quick “bio” breaks in rooms nearest the central nurse station. When nurses left care floors, they preferred the cafeteria and outdoor eating spaces.
Conclusion:
Nurses’ proclivity to minimize restorative breaks remains a major organizational concern. Future studies should investigate leadership activities impacting nurses’ perception of shifts and break-taking behavior.
Application to Practice:
By optimizing the break setting and changing the cultural perspective of breaks, occupational health services and healthcare management can support nurses’ engagement in restorative activities.
During times of nursing shortage and economic downturn, nurse leaders are challenged to find creative ways to recruit, retain, reward, and professionally develop their nursing workforce. Clinical ...ladders are two options frequently reported in the literature. However, both programs may be expensive, time consuming to manage, complex to understand, and difficult to institute in a collective bargaining agreement environment. Here, Lawson et al offer ways on how to recognize nursing professional growth and development in a collective bargaining environment through their Professional Recognition Program, which encompasses elements of traditional clinical ladder programs, such as a reward for obtaining a higher educational degree or achieving specific certification, and is grounded in Patricia Benner's Novice to Expert Model.
Drug survival of biologic therapies for psoriasis is a proxy for longer-term treatment effectiveness and safety. Patient factors that are associated with the survival of each biologic differently ...(effect modifiers) may inform the decision to choose between biologics.
To assess the drug survival associated with the effectiveness and safety of commonly used biologics for psoriasis in the UK and Ireland and identify effect modifiers for these biologics and their survival.
We conducted a prospective cohort study of patients with psoriasis using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2021.
Adalimumab, ustekinumab, secukinumab, guselkumab, ixekizumab.
We conducted a survival analysis and fitted separate flexible parametric models for drug survival as a proxy for effectiveness and safety.
A total of 16 122 treatment courses were included: 6607 (41.0%) in which treatment with adalimumab was initiated, 5405 (33.5%) with ustekinumab, 2677 (16.6%) with secukinumab, 730 (4.5%) with guselkumab, and 703 (4.4%) with ixekizumab. The crude survival functions at year 1 for measures of effectiveness for treatment with adalimumab was 0.81 (95% CI, 0.80-0.82), 0.89 for ustekinumab (95% CI, 0.88-0.89), 0.86 for secukinumab (95% CI, 0.85-0.87), 0.94 for guselkumab (95% CI, 0.92-0.96), and 0.86 for ixekizumab (95% CI, 0.83-0.89). The adjusted survival curves from the multivariable model for effectiveness showed that treatment with guselkumab had the higher survival (adjusted hazard ratio, 0.13; 95% CI, 0.03-0.56) and adalimumab had the lower survival (adjusted hazard ratio, 2.37; 95% CI, 2.03-2.76) compared with ustekinumab. Secukinumab and ixekizumab had similar survival curves over time. Psoriatic arthritis, previous biologic exposure, nail involvement, and ethnicity were effect modifiers for survival in association with treatment effectiveness. The crude survival functions at year 1 for safety were 0.91 for treatment with adalimumab (95% CI, 0.90-0.91), 0.94 for ustekinumab (95% CI, 0.94-0.95), 0.94 for secukinumab (95% CI, 0.92-0.94), 0.96 for guselkumab (95% CI, 0.94-0.98), and 0.92 for ixekizumab (95% CI, 0.89-0.94). Guselkumab, ustekinumab, and secukinumab had similar adjusted survival curves for safety, while adalimumab (adjusted hazard ratio, 1.66; 95% CI, 1.46-1.89) and ixekizumab (adjusted hazard ratio, 1.52; 95% CI, 1.13-2.03) had lower survival compared with ustekinumab.
The results of this cohort study suggest that guselkumab had the highest drug survival in BADBIR of the included biologics for treatment persistence that was associated with effectiveness, and guselkumab had highest drug survival for safety compared with other biologics except ustekinumab. Psoriatic arthritis, nail involvement, previous biologic exposure, and ethnicity were effect modifiers for biologics and their survival in association with treatment effectiveness. This information on longer-term treatment persistence, safety, and tolerability may help patients and their clinicians make an informed decision to initiate treatment with a biologic therapy.
Biologic therapies can be highly effective for the treatment of severe psoriasis, but response for individual patients can vary according to drug. Predictive biomarkers to guide treatment selection ...could improve patient outcomes and treatment cost-effectiveness.
We sought to test whether HLA-C*06:02, the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the 2 most commonly prescribed biologics for psoriasis: adalimumab (anti–TNF-α) and ustekinumab (anti–IL-12/23).
This study uses a national psoriasis registry that includes longitudinal treatment and response observations and detailed clinical data. HLA alleles were imputed from genome-wide genotype data for 1326 patients for whom 90% reduction in Psoriasis Area and Severity Index score (PASI90) response status was observed after 3, 6, or 12 months of treatment. We developed regression models of PASI90 response, examining the interaction between HLA-C*06:02 and drug type (adalimumab or ustekinumab) while accounting for potentially confounding clinical variables.
HLA-C*06:02–negative patients were significantly more likely to respond to adalimumab than ustekinumab at all time points (most strongly at 6 months: odds ratio OR, 2.95; P = 5.85 × 10−7), and the difference was greater in HLA-C*06:02–negative patients with psoriatic arthritis (OR, 5.98; P = 6.89 × 10−5). Biologic-naive patients who were HLA-C*06:02 positive and psoriatic arthritis negative demonstrated significantly poorer response to adalimumab at 12 months (OR, 0.31; P = 3.42 × 10−4). Results from HLA-wide analyses were consistent with HLA-C*06:02 itself being the primary effect allele. We found no evidence for genetic interaction between HLA-C*06:02 and ERAP1.
This large observational study suggests that reference to HLA-C*06:02 status could offer substantial clinical benefit when selecting treatments for severe psoriasis.
Summary
Background
Biologic therapies have revolutionized the treatment of moderate‐to‐severe psoriasis. However, for reasons largely unknown, many patients do not respond or lose response to these ...drugs.
Objectives
To evaluate demographic, social and clinical factors that could be used to predict effectiveness and stratify response to biologic therapies in psoriasis.
Methods
Using a multicentre, observational, prospective pharmacovigilance study (BADBIR), we identified biologic‐naive patients starting biologics with outcome data at 6 (n = 3079) and 12 (n = 3110) months. Associations between 31 putative predictors and outcomes were investigated in univariate and multivariable regression analyses. Potential stratifiers of treatment response were investigated with statistical interactions.
Results
Eight factors associated with reduced odds of achieving ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) at 6 months were identified (described as odds ratio and 95% confidence interval): demographic (female sex, 0·78, 0·66–0·93); social (unemployment, 0·67, 0·45–0·99); unemployment due to ill health (0·62, 0·48–0·82); ex‐ and current smoking (0·81, 0·66–0·99 and 0·79, 0·63–0·99, respectively); clinical factors (high weight, 0·99, 0·99–0·99); psoriasis of the palms and/or soles (0·75, 0·61–0·91); and presence of small plaques only compared with small and large plaques (0·78, 0·62–0·96). White ethnicity (1·48, 1·12–1·97) and higher baseline PASI (1·04, 1·03–1·04) were associated with increased odds of achieving PASI 90. The findings were largely consistent at 12 months. There was little evidence for predictors of differential treatment response.
Conclusions
Psoriasis phenotype and potentially modifiable factors are associated with poor outcomes with biologics, underscoring the need for lifestyle management. Effect sizes suggest that these factors alone cannot inform treatment selection.
What's already known about this topic?
Biologic therapy used in the treatment of moderate‐to‐severe psoriasis differs in its effectiveness across patients.
Previous research has indicated that patients with a higher body mass index, who smoke or who have smoked, and with a lower baseline Psoriasis Area and Severity Index (PASI) are less likely to have a good outcome with biologic therapy for the treatment of moderate‐to‐severe psoriasis.
What does this study add?
This large‐scale study in a real‐world setting confirms that weight, smoking status and baseline PASI are associated with effectiveness of biologic therapy.
There is evidence that non‐white ethnicity, female sex, unemployment, psoriasis of the palms and soles and the presence of small chronic plaques are associated with poor outcomes with biologics.
There is some evidence that men have a comparatively worse response to etanercept, relative to adalimumab, than women. Otherwise, most factors do not appear to be predictors of differential treatment response.
Respond to this article
Medication non-adherence is a missed opportunity for therapeutic benefit. We assessed “real-world” levels of self-reported non-adherence to conventional and biologic systemic therapies used for ...psoriasis and evaluated psychological and biomedical factors associated with non-adherence using multivariable analyses. Latent profile analysis was used to investigate whether patients can be categorized into groups with similar medication beliefs. Latent profile analysis categorizes individuals with similar profiles on a set of continuous variables into discrete groups represented by a categorical latent variable. Eight hundred and eleven patients enrolled in the British Association of Dermatologists Biologic Interventions Register were included. Six hundred and seventeen patients were using a self-administered systemic therapy; 22.4% were classified as “non-adherent” (12% intentionally and 10.9% unintentionally). Patients using an oral conventional systemic agent were more likely to be non-adherent compared to those using etanercept or adalimumab (29.2% vs. 16.4%; P ≤ 0.001). Latent profile analysis supported a three-group model; all groups held strong beliefs about their need for systemic therapy but differed in levels of medication concerns. Group 1 (26.4% of the sample) reported the strongest concerns, followed by Group 2 (61%), with Group 3 (12.6%) reporting the weakest concerns. Group 1 membership was associated with intentional non-adherence (odds ratio = 2.27, 95% confidence interval = 1.16−4.47) and weaker medication-taking routine or habit strength was associated with unintentional non-adherence (odds ratio = 0.92, 95% confidence interval = 0.89−0.96). Medication beliefs and habit strength are modifiable targets for strategies to improve adherence in psoriasis.
Patients with psoriasis enrolled in clinical trials of biologics may not be representative of the real-world population. There is evidence that patients ineligible for such trials have a greater risk ...of serious adverse events (SAEs), but the effect on drug discontinuation and effectiveness are unknown.
To determine whether (1) drug discontinuation, (2) effectiveness, and (3) rates of SAEs differ in patients with psoriasis categorized as eligible or ineligible for clinical trials.
An observational study using 157 dermatology centers in the United Kingdom and Republic of Ireland was carried out wherein we applied the eligibility criteria of clinical trials of biologic therapies for psoriasis to patients who were being followed up in the British Association of Dermatologists Biologic Interventions Register (BADBIR) and being prescribed biologics as part of standard clinical care. Patients with psoriasis registered to BADBIR who were taking etanercept (enbrel only; n = 1509), adalimumab (n = 4000), and ustekinumab (n = 1627) with at least 1 follow-up visit. Eligibility criteria were extracted from phase 3 licensing trials for etanercept, adalimumab, and ustekinumab for the treatment of moderate to severe psoriasis. Patients in BADBIR with a missing baseline Psoriasis Area and Severity Index (PASI) or baseline PASI value less than 10 (etanercept) or less than 12 (adalimumab; ustekinumab) but who would otherwise be eligible were investigated separately. Eligibility categories applied to BADBIR included: eligible, ineligible, insufficient baseline PASI only, and missing baseline PASI only.
(1) Drug discontinuation: cumulative incidence at 12 months by stop reason per eligibility category and drug; (2) effectiveness: linear regression of absolute change in PASI from baseline to 6 and 12 months; and (3) SAEs: incidence rate ratio (IRR) at 12 months between eligibility categories per drug.
The mean (SD) age of the 7136 patients included in the analysis was 45 (13) years and 2924 (41%) were women and 4212 (59%) were men. Of 7136 patients, 839 (56%) etanercept, 2219 (56%) adalimumab, and 754 (46%) ustekinumab registrations were categorized as eligible. The most common reasons for ineligibility were diabetes (etanercept, 143 9%; ustekinumab, 201 12%) and nonchronic plaque psoriasis (adalimumab, 157 4%). Patients categorized as ineligible (etanercept, 367 24%; adalimumab, 282 7%; ustekinumab, 394 24%) achieved a smaller absolute change in PASI after 6 and 12 months (adalimumab, ustekinumab), and had significantly higher rates of SAEs compared with the eligible category (etanercept: IRR, 1.9; 95% CI, 1.4-2.6; adalimumab: IRR, 2.0; 95% CI, 1.5-2.6; ustekinumab: IRR, 2.8; 95% CI, 2.1-3.8). No significant differences in drug discontinuation were observed between categories.
Clinical trial effectiveness and safety outcomes are not representative of real-world patients in BADBIR patients categorized as ineligible for such trials.
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