Value-Based Healthcare: A primer for the dermatologist.

BACKGROUND: Value-based healthcare (VBHC) is an increasingly employed strategy to transform healthcare organizations into economically sustainable systems that deliver high-value care. In dermatology, the need for VBHC is evident as chronic skin diseases require long-term, often expensive treatments. This narrative review aims to introduce dermatologists to the principles and implementation of VBHC. SUMMARY: VBHC emphasizes maximizing outcomes that are directly relevant to patients. Key components of VBHC include a systematic assessment of standardized patient-relevant outcomes by using core outcome sets and measurement of healthcare cost for the individual patient. Systematic reporting and comparing of risk-adjusted outcomes across the full cycle of care for a specific condition provide benchmarked feedback and actionable insights to promote high-value care and reduce low-value care. VBHC aims to organize care around the patient in condition-specific and team-based integrated practice units with multidisciplinary collaboration, utilize information technology platforms to enable digital data monitoring, reduce cost and eventually reform payment systems to support bundled payments for the overall care cycle. VBHC implementation in practice necessitates the establishment of a systematic framework for outcome-based quality improvement, the incorporation of value and outcomes in shared decision-making practices, and the cultivation of a value-centric culture among healthcare professionals through continuous training. Key-messages: Dermatologists can benefit from implementing VBHC principles in their practice. An essential step towards value-driven dermatological care is to start measuring outcomes relevant for patients for each patient, which is lacking partly due to the absence of core outcome sets developed for clinical practice. By reducing low-value care and emphasizing optimal patient-centered outcomes, VBHC has the potential to improve the quality of care and ensuring cost-containment. Efforts are needed to enhance the development and uptake of VBHC in dermatological clinical practice to realize these benefits.

Initiating value-based healthcare in psoriasis: Proposing a value-based outcome set for daily clinical practice.

BACKGROUND: With the current trend in healthcare moving towards a more value-based approach, it is essential to understand what value encompasses. OBJECTIVES: To develop an actionable value-based outcome set (VOS) for daily practice. METHODS: A mixed method approach was used consisting of four phases. Formerly, a systematic review was conducted, providing an overview of all patient-relevant outcomes defined in current literature. These 23 outcomes were then presented to a group of patients, using a modified nominal group technique (NGT), to establish whether these results represented all of their relevant outcomes. Subsequently, these outcomes were ranked according to importance by patients attending our academic specialized psoriasis clinic. A review of the literature was performed to assess which instruments were available and suitable to evaluate the outcomes in this VOS. Finally, a pilot feasibility test was performed amongst patients. RESULTS: Of the 23 outcomes, two were omitted from the ranking exercise after the NGT. In the ranking exercise, 120 patients participated. The median age was 50.0 (IQR 25.0) years and 36.7% were female. Median PASI score was 2.4 (IQR 5.2), and treatments varied from topicals to biologicals. The outcomes scored as most important were symptom control, treatment efficacy, confidence in care and control of disease. The least important outcomes were comorbidity control, productivity and cost of care. A significant difference was shown between the ranking of the outcomes (p < 0.001). In total, 12 instruments were selected, which are reported by both patient and provider, to measure the outcomes in this VOS. Median completion time for the patient part was 30 min (IQR 2.8). CONCLUSIONS: This VOS is a first proposal to evaluate psoriasis care in a value-based manner. Measuring these outcomes can enable us to critically appraise and improve current care processes, within the reality of available resources, thereby increasing value for patients.

Systemic glucocorticoid use and the occurrence of flares in psoriatic arthritis and psoriasis: a systematic review.

OBJECTIVES: The use of systemic glucocorticoids (SGCs) is traditionally discouraged in the treatment of PsA and psoriasis due to the risk of psoriatic flares. However, despite this recommendation, SGCs are frequently prescribed for these patients. In this study we reappraise the old paradigm that SGCs are contra-indicated in the treatment of PsA and psoriasis. METHODS: A systematic search of MEDLINE, EMBASE and the Cochrane Library databases was performed in November 2019 to identify articles on any SGC use compared with no use in the PsA and psoriasis population. Topical glucocorticoid treatment was excluded. Our two primary outcomes focused on the prescribing characteristics and the occurrence of any type of flare. RESULTS: Our search yielded 4922 articles, and of these 21 full-text articles were eligible for inclusion. There were 11 retro- and prospective cohorts involving a total of 4,171,307 patients. Of these, 6727 (37.82%) of the patients with PsA and 1 460 793 (35.17%) of the patients with psoriasis were treated with any type of SGC. Ten observational/interventional studies did not report an increased risk or occurrence of psoriatic flares related to SGC use. CONCLUSION: Our results indicate that SGCs are frequently prescribed for PsA and psoriasis patients. The occurrence of psoriatic flares appears to be low upon SGC exposure. In patients with a clear indication for SGCs, e.g. in need of rapid anti-inflammatory therapy or bridging of therapies, the use of SGCs should be considered in view of the low risk of skin flaring. It remains of importance to weigh risks for short- and long-term SGC-related side effects in clinical decision making.

Do Patients with Psoriatic Arthritis Have More Severe Skin Disease than Patients with Psoriasis Only? A Systematic Review and Meta-Analysis.

BACKGROUND: Early identification of patients at risk of psoriatic arthritis (PsA) is essential to facilitate early diagnosis and improve clinical outcomes. Severe cutaneous psoriasis has been proposed to be associated with PsA, but a recent assessment of the evidence is lacking. Therefore, in this systematic review, we address the association of psoriasis skin severity with the presence and development of PsA. SUMMARY: We included articles from a review published in 2014 and supplemented these with recent literature by performing an additional systematic search to identify studies published between 1 January 2013 and 11 February 2021. A meta-analysis was performed when sufficient comparable evidence was available. Of 2,000 screened articles, we included 29 in the analysis, of which 16 were identified by our updated search. Nineteen studies reported psoriasis severity as psoriasis area and severity index (PASI), ten studies as body surface area (BSA), and two studies as "number of affected sites." Most studies show that more extensive skin disease is associated with the presence of PsA. The quantitative pooled analyses demonstrate higher PASI (mean difference [Δ] 1.59; 95% confidence interval [CI] 0.29-2.89) and higher BSA (Δ 5.31; 95% CI 1.78-8.83) in patients with PsA as compared to psoriasis patients without PsA. Results from prospective studies - that assess the risk of future development of PsA in psoriasis patients - were inconclusive. KEY MESSAGES: In patients with psoriasis, more severe skin involvement is associated with the presence of PsA, underpinning the importance of optimal dermatology-rheumatology collaboration in clinical care. There are insufficient data to support the use of psoriasis skin severity to predict the future development of PsA in psoriasis patients.

Broad proteomic screen reveals shared serum proteomic signature in patients with psoriatic arthritis and psoriasis without arthritis.

OBJECTIVE: To identify novel serum proteins involved in the pathogenesis of PsA as compared with healthy controls, psoriasis (Pso) and AS, and to explore which proteins best correlated to major clinical features of the disease. METHODS: A high-throughput serum biomarker platform (Olink) was used to assess the level of 951 unique proteins in serum of patients with PsA (n = 20), Pso (n = 18) and AS (n = 19), as well as healthy controls (HC, n = 20). Pso and PsA were matched for Psoriasis Area and Severity Index (PASI) and other clinical parameters. RESULTS: We found 68 differentially expressed proteins (DEPs) in PsA as compared with HC. Of those DEPs, 48 proteins (71%) were also dysregulated in Pso and/or AS. Strikingly, there were no DEPs when comparing PsA with Pso directly. On the contrary, hierarchical cluster analysis and multidimensional scaling revealed that HC clustered distinctly from all patients, and that PsA and Pso grouped together. The number of swollen joints had the strongest positive correlation to ICAM-1 (r = 0.81, P < 0.001) and CCL18 (0.76, P < 0.001). PASI score was best correlated to PI3 (r = 0.54, P < 0.001) and IL-17 receptor A (r = -0.51, P < 0.01). There were more proteins correlated to PASI score when analysing Pso and PsA patients separately, as compared with analysing Pso and PsA patients pooled together. CONCLUSION: PsA and Pso patients share a serum proteomic signature, which supports the concept of a single psoriatic spectrum of disease. Future studies should target skin and synovial tissues to uncover differences in local factors driving arthritis development in Pso.

Dupilumab is very effective in a large cohort of difficult-to-treat adult atopic dermatitis patients: First clinical and biomarker results from the BioDay registry.

INTRODUCTION: Dupilumab has recently been approved for the treatment of moderate to severe atopic dermatitis (AD) in adults. Daily practice data on dupilumab treatment are scarce. OBJECTIVE: To study the effect of 16-week treatment with dupilumab on clinical response and serum biomarkers in adult patients with moderate-severe AD in daily practice. METHODS: Data were extracted from the BioDay registry, a prospective multicenter registry. Sixteen-week clinical effectiveness of dupilumab was expressed as number of patients achieving EASI-50 (Eczema Area and Severity Index) or EASI-75, as well as patient-reported outcomes measures (Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Numeric Rating Scale pruritus). Twenty-one biomarkers were measured in patients treated with dupilumab without concomitant use of oral immunosuppressive drugs at five different time points (baseline, 4, 8, 12, and 16 weeks). RESULTS: In total, 138 patients treated with dupilumab in daily practice were included. This cohort consisted of patients with very difficult-to-treat AD, including 84 (61%) patients who failed treatment on ≥2 immunosuppressive drugs. At week 16, the mean percent change in EASI score was 73%. The EASI-50 and EASI-75 were achieved by 114 (86%) and 82 (62%) patients after 16 weeks of treatment. The most reported side effect was conjunctivitis, occurring in 47 (34%) patients. During dupilumab treatment, disease severity-related serum biomarkers (TARC, PARC, periostin, and IL-22), eotaxin-1, and eotaxin-3 significantly decreased. CONCLUSION: Treatment with dupilumab significantly improved disease severity and decreased severity-related serum biomarkers in patients with very difficult-to-treat AD in a daily practice setting.

IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Aberrant toll-like receptors (TLRs) 7, 8, and 9 activation by self-nucleic acids is implicated in immune-mediated inflammatory diseases (IMIDs) such as psoriasis. In preclinical IMID models, blocking TLR-activation reduced disease severity. IMO-8400 is a first-in-class, oligonucleotide-based antagonist of TLRs 7, 8, and 9. We evaluated the short-term safety and proof-of-concept for efficacy of IMO-8400 in a first-in-patient phase 2 trial. METHODS: Forty-six psoriasis patients were randomly assigned to IMO-8400 in four dose levels or placebo for 12weeks. Post-treatment follow-up was seven weeks. Primary outcome was incidence of adverse events. Secondary, exploratory outcomes included changes in psoriasis area and severity index (PASI). RESULTS: IMO-8400 across all dose levels did not cause any serious or severe adverse events. The most common treatment-related adverse events were dose-dependent injection-site reactions. All IMO-8400 groups showed clinical improvement, but a clear dose-response relationship and statistically significant differences with placebo were not observed (P=0.26). Eleven (38%) of 29 subjects on IMO-8400 achieved ≥50% PASI-reduction, compared to 1 (11%) of 9 subjects on placebo. Five (17%) and 2 (7%) IMO-8400-treated subjects achieved PASI-75 and PASI-90, respectively, compared to none on placebo. CONCLUSIONS: Short-term IMO-8400-treatment was well tolerated and reduced psoriasis severity. These findings warrant further investigation of endosomal TLR-antagonism as a therapeutic approach in psoriasis and other TLR-mediated IMIDs. TRIAL REGISTRATION: EudraCT 2013-000164-28 and Clinicaltrials.govNCT01899729.

Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study.

BACKGROUND: Biologics are a safe and efficacious therapy for psoriasis. The drug survival of biologics may be disappointing, primarily due to loss of efficacy. Therefore, safe combination treatments are sought to improve their clinical response. OBJECTIVE: To assess the efficacy, safety and tolerability of the combination therapy of etanercept with fumarates versus etanercept monotherapy. METHODS: Thirty-three patients with psoriasis were randomized 1:1 to receive etanercept combined with fumarates or etanercept monotherapy. The primary outcome measure was the difference in PASI-75 response after 24 weeks; additionally, a longitudinal analysis was performed. An important secondary outcome measure was the proportion of patients with a Physician Global Assessment (PGA) of clear or almost clear. Adverse events were collected throughout the study. RESULTS: In the combination therapy group, 78% (14 out of 18 patients) reached PASI-75 at week 24 versus 57% (8 out of 14 patients) in the monotherapy group (p = 0.27). The longitudinal analysis showed a PASI reduction of 5.97% per week for the combination therapy group and of 4.76% for the monotherapy group (p = 0.11). In the combination therapy group, 94% (17 out of 18 patients) of patients had a PGA of clear/almost clear versus 64% (9 out of 14 patients) in the monotherapy group (p = 0.064). The incidence of mild gastrointestinal complaints was higher in the combination group than in the monotherapy group. CONCLUSION: Using the PGA, combination therapy showed a trend towards faster improvement in the first 24 weeks. The difference in the PASI score between the two groups was not statistically significant. Addition of fumarates to etanercept for 48 weeks appeared safe with an acceptable tolerability.

A benchmark for comparison of cell tracking algorithms.

MOTIVATION: Automatic tracking of cells in multidimensional time-lapse fluorescence microscopy is an important task in many biomedical applications. A novel framework for objective evaluation of cell tracking algorithms has been established under the auspices of the IEEE International Symposium on Biomedical Imaging 2013 Cell Tracking Challenge. In this article, we present the logistics, datasets, methods and results of the challenge and lay down the principles for future uses of this benchmark. RESULTS: The main contributions of the challenge include the creation of a comprehensive video dataset repository and the definition of objective measures for comparison and ranking of the algorithms. With this benchmark, six algorithms covering a variety of segmentation and tracking paradigms have been compared and ranked based on their performance on both synthetic and real datasets. Given the diversity of the datasets, we do not declare a single winner of the challenge. Instead, we present and discuss the results for each individual dataset separately. AVAILABILITY AND IMPLEMENTATION: The challenge Web site (http://www.codesolorzano.com/celltrackingchallenge) provides access to the training and competition datasets, along with the ground truth of the training videos. It also provides access to Windows and Linux executable files of the evaluation software and most of the algorithms that competed in the challenge.

Is mipomersen ready for clinical implementation? A transatlantic dilemma.

PURPOSE OF REVIEW: Mipomersen has been approved by the US Food and Drug Administration as an orphan drug for patients with homozygous familial hypercholesterolemia (HoFH). In contrast, the European Medicines Agency advised negatively on the use of mipomersen. In this review, we discuss the efficacy and safety considerations for this discrepancy. RECENT FINDINGS: On the basis of the results of clinical trials with mipomersen, safety concerns have been raised regarding cardiovascular risk reduction and development of hepatic steatosis. In addition, (long-term) tolerability concerns have been raised predominantly regarding injection site reactions. A pooled analysis of cardiovascular events in phase III trials with mipomersen did not provide evidence for either a positive or negative effect on cardiovascular disease. Although long-term studies with mipomersen are eagerly awaited, hepatic fat content appears to stabilize after 6-12 months notwithstanding continued mipomersen administration. SUMMARY: HoFH is a disease with an unmet medical need for new lipid-lowering therapies. On the basis of a mean 2.9 mmol/l LDL-cholesterol reduction, mipomersen is expected to reduce cardiovascular risk in HoFH. Available evidence suggests that the fat accumulation associated with this treatment differs from steatohepatitis, which is a progressive and damaging liver disease. No evidence is available suggesting that injection site reactions because of mipomersen treatment will result in safety issues.

Patient-Reported Outcome Measures for Health-Related Quality of Life in Patients With Psoriasis: A Systematic Review.

Importance: Multiple patient-reported outcome measures (PROMs) for health-related quality of life (HRQL) exist for patients with psoriasis. Evidence for the content validity and other measurement properties of these PROMs is critical to determine which HRQL PROMs could be recommended for use. Objective: To systematically review the validity of HRQL-focused PROMs used in patients with psoriasis. Evidence Review: Using PubMed and Embase, full-text articles published in English or Spanish on development or validation studies for psoriasis-specific, dermatology-specific, or generic HRQL PROMs were included. Development studies included original development studies, even if not studied in psoriasis patients per Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) recommendations. If a study included multiple diagnoses, more than 50% of patients had to have psoriasis or psoriasis-specific subgroup analyses available. Data extraction and analysis followed the COSMIN guidelines. Two independent reviewers extracted and analyzed the data, including PROM characteristics, quality of measurement properties (structural validity, internal consistency, cross-cultural validity, reliability, measurement error, criterion validity, construct validity, and responsiveness), and level of evidence. PROMs were classified into 3 levels of recommendations: (1) PROM recommended for use; (2) PROM requires further validation; and (3) PROM not recommended for use. Findings: Overall, 97 articles were identified for extraction. This included 19 psoriasis-specific, 8 skin-specific, and 6 generic PROMs. According to COSMIN standards, most measures identified received a B recommendation for use, indicating their potential but requiring further validation. Only the Rasch reduced version of the Impact of Psoriasis Questionnaire (IPSO-11 Rasch) received an A recommendation for use given that it had sufficient content validity, structural validity, and internal consistency. Conclusions and Relevance: This study identified a significant lack of information concerning the quality of HRQL measures in psoriasis. This gap in knowledge can be attributed to the fact that traditional measures were developed using validation criteria that differ from the current standards in use. Consequently, additional validation studies in accordance with contemporary standards will be useful in aiding researchers and clinicians in determining the most suitable measure for assessing HRQL in patients with psoriasis.