A value-based healthcare model for initiating and switching psoriasis therapies-Results from the prospective multicentre IMPROVE study.

BACKGROUND: Little is known about the therapeutic benefits of a value-based healthcare model compared to a traditional activity-based incentive model in psoriasis (PsO). OBJECTIVES: This prospective non-interventional study evaluated an outcome-based, patient-centred management model for patients with PsO. METHODS: In total, 49 patients with a Psoriasis Area and Severity Index (PASI) ≥3 who were starting or switching between treatments were included. Patients were assessed at baseline, 3 and 9 months. The patient benefit index (PBI) was calculated using predefined questionnaires. An expected PBI was calculated and adjusted for risk factors known to complicate treatment, that is overweight and smoking. The model remunerated the department on whether the observed PBI exceeded the expected PBI to incentivize over-performance. RESULTS: In total, 40 patients (80%) completed all three visits; 32.7% were smokers and 73.5% were overweight. Mean PASI at baseline was 11.5 (SD 9.1); PASI improved significantly from baseline through 3 months: mean reduction, 8.0 (SD 9.2), p < 0.001 and was maintained until 9 months: mean further reduction, 0.1 (SD 3.3), p = 0.893. The mean PBI was 2.5 (SD 1.3) and 2.8 (SD 1.1) at 3 and 9 months, respectively. A PBI ≥1 was achieved by 87.8% at 3 and 95.1% at 9 months. Overall, the department was remunerated a mean 2721.1 DKK (SD 4472.8) per patient. In subgroup analysis, the department was remunerated a mean of, respectively, 2428.6 (SD 5089.5), 2636.6 (SD 4471.3) and 3196.5 (SD 4497.1) DKK for patients with none, 1 or 2 risk factors, that is smoking or/and overweight. CONCLUSIONS: The model evaluated herein is the first value-based model to calculate remuneration from patient reported outcomes and showed to successfully predict the expected PBI and remunerate treatment based on whether the expected treatment goal was met or exceeded. This can be utilized in the patient-centred management of PsO.

Prevalence of and association between atopic dermatitis and food sensitivity, food allergy and challenge-proven food allergy: A systematic review and meta-analysis.

Atopic dermatitis (AD) and food allergy (FA) share similar type 2 inflammation and commonly co-occur, but the precise proportion of AD patients with FA and vice versa, as well as the effect of AD disease severity on the strength of this association remains uncertain. The aim of this comprehensive systematic review and meta-analysis was to determine the prevalence and bidirectional associations of AD with food sensitivity (FS), FA and challenge-proven food allergy (CPFA). We searched PubMed and EMBASE and three independent reviewers performed title/abstract and full-text review and data extraction. Overall, 557 articles (n = 225,568 individuals with AD, n = 1,128,322 reference individuals; n = 1,357,793 individuals with FS, FA or CPFA, n = 1,244,596 reference individuals) were included in quantitative analyses. The overall pooled prevalence of FS, FA and CPFA in individuals with AD were 48.4% (95% confidence interval: 43.7-53.2), 32.7% (28.8-36.6) and 40.7% (34.1-47.5) respectively. AD prevalence among individuals with FS, FA and CPFA were 51.2% (46.3-56.2), 45.3% (41.4-49.3) and 54.9% (47.0-62.8) respectively. Children with AD had higher pooled FS (49.8% (44.4-55.1)) and FA (31.4% (26.9-36.1)) prevalences than adults with AD (28.6% (13.4-46.8) and 24.1% (12.1-38.7) respectively). Prevalences of FS and FA numerically increased with AD severity. FS, FA and CPFA are common comorbidities of AD and are closely related. Physicians should be attentive to this relationship to optimize management and treatment strategies in patients.

Antimicrobial peptides in hidradenitis suppurativa: a systematic review.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease of the hair follicle defined by recurrent nodules, tunnels and scarring involving the intertriginous regions. HS is associated with microbial dysbiosis and immune dysregulation. In HS, an increasing number of studies have investigated antimicrobial peptides (AMPs). OBJECTIVES: To provide an overview of the literature on AMPs in HS, and to discuss the potential role of AMPs in the pathogenesis of HS. METHODS: PubMed, Embase and the Cochrane Library were searched. The titles, abstracts and full texts of all articles were manually screened. Additionally, the reference lists of the included articles were screened and hand searched for relevant studies. RESULTS: The final literature sample comprised 18 retrospective and prospective studies (no reviews or commentaries) published between 2009 and 2020. CONCLUSIONS: This review demonstrates the multitude of AMPs in HS. Although the methodology of the studies varied, the included studies indicate a consistent overexpression of human ß-defensin (hBD)-2, S100A7, S100A8 and S100A9 at both the mRNA and protein levels, and a decreased expression of hBD-1. Overall, the studies point to a dysregulation of AMPs in both lesional and nonlesional HS skin.

Adults with concomitant atopic dermatitis and asthma have more frequent urgent healthcare utilization and less frequent scheduled follow-up visits than adults with atopic dermatitis or asthma only: a nationwide cohort study.

BACKGROUND: Atopic dermatitis (AD) and asthma often co-occur in the same patient, and healthcare utilization is related to disease severity of these diseases. OBJECTIVE: The objective of the study was to investigate differences in healthcare utilization in adults with concomitant AD and asthma compared to patients with asthma or AD only. METHODS: All Danish adults with a hospital diagnosis of AD, asthma or concomitant AD, and asthma recorded in national registries were included. Healthcare utilization data were obtained in 3-month intervals from 2 years prior to index date (the date of the first hospital diagnosis) and to 5 years after. RESULTS: A total of 12 409 patients with AD were included (11 590 with AD only and 819 with concomitant AD and asthma), and 65 539 with asthma only. Adults with concomitant AD and asthma had higher risk of hospitalization for AD (OR 1.38, 95% CI (1.15-1.67), P = 0.001) and asthma (OR 1.16, 95% CI (1.00-1.35), P = 0.047) compared to patients with only AD and asthma, respectively. These patients also had fewer visits in outpatient clinics for AD (OR 0.10, 95% CI (0.08-0.12), P < 0.001) and asthma (OR 0.34, 95% CI (0.29-0.39), P < 0.001) compared to patients with only AD or asthma. Outpatient clinic visits for rhinitis were more frequent among patients with concomitant AD and asthma compared to patients with only AD or asthma. CONCLUSION: Adults with concomitant AD and asthma had different patterns of healthcare utilization compared to adults with AD or asthma alone, suggesting that improvements in management and monitoring may reduce unscheduled healthcare visits and lower healthcare costs.

Burden, predictors and temporal relationships of comorbidities in patients with hidradenitis suppurativa: a hospital-based cohort study.

AIM: To examine the burden, predictors and temporal relationships of comorbidities in patients with hidradenitis suppurativa (HS). METHODS: Information on HS and ten systemic comorbidities was obtained by interview and clinical examination, including blood pressure, body mass index (BMI) and blood samples, in a cohort of consecutive HS outpatients. RESULTS: A total of 302 patients were included. About 86.6% had at least one comorbidity. The mean number of comorbidities per patient was 2.1. One or more cardiovascular comorbidities were observed in 76.5% with evidence of substantial unawareness and undertreatment; 48.4% had hypertension, 9.3% had diabetes, 57.7% had dyslipidaemia and 36.7% were obese. About 6.6% had inflammatory bowel disease, 6.3% had arthritis, 29.5% had a psychiatric diagnosis, 5.6% had psoriasis, 7.9% had obstructive lung disease, and 6.6% had polycystic ovary syndrome. These comorbidities occurred at different time points in relation to the onset of HS with evidence of shared as well as differential risk factors. Age (per year), HR = 0.87 (0.79-0.96), P < 0.006, age of onset of HS (per year), HR = 1.26 (1.14-1.40), P < 0.001, male sex, HR = 2.51 (0.88-7.16), P = 0.086, Hurley stage III (vs. Hurley I + II), HR = 3.46 (1.25-9.58), P = 0.017, BMI (per unit), HR = 1.12 (1.04-1.20), P = 0.002, and blood glucose (per unit), HR = 1.27 (1.16-1.39), P < 0.001 were significant predictors for onset of diabetes. CONCLUSION: There is a substantial burden, unawareness and undertreatment of several systemic comorbidities in patients with HS. Comorbidities occur at different time points in relation to the onset of HS. This should lead to higher awareness among treating specialists.

Atopic dermatitis is associated with increased use of social benefits: a register-based cohort study.

BACKGROUND: The comprehensive consequences of atopic dermatitis (AD) include a negative influence on work life. However, data regarding use of social benefits in patients with AD are sparse. OBJECTIVE: To examine the association between AD and use of social benefits, with a specific focus on paid sick leave and disability pension. METHODS: The study cohort comprises citizens born in the period 1964-1999 with a diagnosis of AD registered in the Danish National Patient Registry (DNPR) and a 20-fold match control group from the background population. Cross-linkage of data from 1964 up to 2015 by four national registers (the DNPR; the Central Person Register; the Register of Medicinal Product Statistics; and the Danish Register for Evaluation of Marginalisation) enabled the comparison of AD patients and controls with respect to social benefits. Prescription of systemic medication served as a proxy for AD severity. Social benefits were analysed as a function of AD status using Cox regression. RESULTS: A total of 28 156 AD patients were registered in the DNPR, and the control group comprised 473 836 individuals not registered with AD in the DNPR. AD was found to be associated with increased risk of receiving social benefits, paid sick leave in particular, and most pronounced for younger patients with severe AD (OR = 1.37, 95% CI: 1.25-1.52). The use of disability pension was increased for all groups of AD patients compared to controls and most pronounced for older patients with severe AD [HR 1.67 (95% CI: 1.45-1.93)]. CONCLUSION: Our data emphasize that AD significantly impacts work life negatively for the patients and is a financial burden for the society.

Cause-specific mortality in patients with psoriasis and psoriatic arthritis.

BACKGROUND: There are limited data regarding causes of mortality in patients with psoriasis or psoriatic arthritis (PsA). OBJECTIVES: This retrospective cohort study evaluated the risk and leading causes of mortality in patients with psoriasis or PsA. METHODS: Individuals with a hospital-based diagnosis of PsA or psoriasis were identified using the Danish National Patient Registry. Matched control individuals were identified from the general population. The main outcome measures were risk of death and cause-specific mortality in patients with psoriasis or PsA. RESULTS: Death rates per 1000 patient-years (with 95% confidence intervals) vs. controls were 22·3 (19·7-24·9) vs. 13·9 (11·8-16·0) for patients with psoriasis and 10·8 (8·9-12·8) vs. 11·6 (9·6-13·6) for patients with PsA. Survival, according to stratified hazard ratios (HRs), was significantly lower in patients with psoriasis than in controls (HR 1·74, P < 0·001), but not in patients with PsA (HR 1·06, P = 0·19). Significantly increased risk of death was observed in patients with psoriasis vs. controls due to a number of causes; the highest risks were observed for diseases of the digestive system; endocrine, nutritional and metabolic diseases; and certain infectious and parasitic diseases (HRs 3·61, 3·02 and 2·71, respectively). In patients with PsA, increased mortality was observed only for certain infectious and parasitic diseases (HR 2·80) and diseases of the respiratory system (HR 1·46). Patients with psoriasis died at a younger age than controls (mean age 71·0 vs. 74·5 years, P < 0·001). CONCLUSIONS: Patients with severe psoriasis have increased mortality risk compared with matched controls, due to a number of causes. Evidence to support an increased risk for patients with PsA was less convincing.

Treatment of atopic dermatitis with dupilumab: experience from a tertiary referral centre.

BACKGROUND: Management of moderate-to-severe atopic dermatitis (AD) frequently requires treatment with systemic therapies. Dupilumab is the first biological agent approved for treatment of moderate-to-severe AD. Although promising results have appeared in clinical trials, real-life data on efficacy and safety are lacking. OBJECTIVES: To assess effectiveness and safety of treatment with dupilumab in the real-life clinical setting at a Danish tertiary referral centre. METHODS: All patients with AD treated with dupilumab from October 2017 to October 2018 at Bispebjerg Hospital, Denmark, were included in the study. Patients were evaluated three times: at treatment initiation and at 1 and 3 months after first dupilumab injection. At each visit, disease activity was assessed by severity score (Eczema Area and Severity Index, EASI), patient-reported outcomes (Dermatology Life Quality Index, DLQI, pruritus and sleep score) and serological markers [immunoglobulin (Ig)E, eosinophil count and lactate dehydrogenase (LDH)]. RESULTS: A total of 43 patients were included in the study. The mean reduction in EASI score from baseline was 19.6 points (72.4%) at 1-month and 22.6 points (76.7%) at 3-month follow-up. EASI, DLQI, pruritus score, sleep score, IgE and LDH were all statistically significantly reduced between baseline and 1- and 3-month follow-up. Mean reductions in EASI score and LDH at 3-month follow-up were significantly correlated (P = 0.003). One patient (2.3%) discontinued treatment due to side-effects, and seven patients (18.4%) developed conjunctivitis during the study period. CONCLUSION: The effectiveness and safety of dupilumab treatment in a real-life clinical setting are comparable to that of phase 3 clinical trials. LDH is suggested as a potential serological marker predictive of treatment response.

Is atopic dermatitis associated with obesity? A systematic review of observational studies.

Obesity has been associated with atopic dermatitis (AD); however, the results have been conflicting. Our aim was to provide an update on current knowledge from observational studies addressing the possible association between obesity and AD. Systematic literature review was performed by identifying studies addressing a possible link between AD and overweight/obesity from PubMed, EMBASE and the Cochrane Library in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. A total of 45 studies (comprising more than 90 000 individuals with AD) fulfilled the criteria and were included in the present review. The available studies revealed inconsistencies, but the majority indicated that obesity is associated with AD. Studies addressing obesity in infancy or early childhood (age < 2 years) and AD reported a positive association. From childhood into adulthood, there is a discrepancy in the observations, as the more recent prospective studies found a positive association, whereas this was not observed in older cross-sectional studies. The inconsistency might be explained by the difference in study design, the diagnostic criteria of AD, regional differences, and by the varied definitions of overweight and obesity used in the studies. In Conclusion, overweight/obesity is associated with an increased risk of AD. Large prospective cohort studies are required to confirm the association between AD and obesity and the possibility that weight control in childhood may help to mitigate or reverse AD symptoms.

Effectiveness of omalizumab in chronic spontaneous urticaria assessed with patient-reported outcomes: a prospective study.

AIM: To examine the effectiveness of omalizumab (anti-IgE) on symptoms and disease-related quality of life in chronic spontaneous urticaria (CSU) and to identify possible patient-specific factors associated with response to omalizumab in patients with antihistamine refractory CSU. METHODS: Six months prospective trial of omalizumab 300 mg every 4 weeks among patients with CSU from a dermatological university department. The primary outcome was the urticaria activity score in the past week (UAS7) at 3 months. RESULTS: A total of 117 patients (39 men and 78 women) with a mean age of 42 years were included. The mean baseline UAS7 score was 29.3 points (SD = 10.8), which improved to 11.9 points (SD = 12.9) at 3 months follow-up, difference = 17.4 points (95% CI: 14.8-19.9), P < 0.0001. Other patient-reported outcomes (PROs) also improved significantly during 3 months of treatment. No significant further improvement was seen between three and 6 months follow-up. None of the following patient-specific factors: sex, age, age of onset of CSU, symptom duration, presence of chronic inducible urticaria (CINDU), comorbidities, positive urticaria HR test, smoking, ethnicity, angio-oedema, serum total IgE level, CRP, leucocytes, absolute neutrophil count or previous treatment with prednisolone or montelukast were significantly associated with response to omalizumab at 3 months, P > 0.05 for all comparisons. Previous treatment with traditional immunosuppressant drugs (azathioprine, cyclosporine or methotrexate) was associated with poorer treatment response to omalizumab at 3 months, P < 0.001. A strong correlation was seen between different patient-reported outcomes (PROs) at baseline and 3 months follow-up. Fifteen patients (12.8%) reported side-effects of the treatment. CONCLUSION: Omalizumab is a highly effective therapy for antihistamine refractory CSU with treatment effects similar to those observed in randomized controlled trials. Validated PROs to assess disease activity, disease control and impairment of quality of life are valuable tools in the clinical management of CSU. Identification of patient-specific predictors of effect and safety of omalizumab in CSU is still warranted.

The impact of atopic dermatitis on work life - a systematic review.

Atopic dermatitis (AD) has considerable multidimensional personal and societal costs. However, the extend to which the patient's work life is affected due to AD is more sparsely described in the literature. The objective of this review was to examine the impact on work life for patients with AD, with a specific focus on choice of education and occupation, sick leave, social compensations and change of job due to AD. A systematic literature search was performed in PubMed, EMBASE and Web og Science up to 7 February 2017 for articles on the impact on work life for patients with AD. Results were summarized taking several measures of study quality into account. The search identified twenty-three articles, whereof five studies assessed the influence of AD on educational or job choice, without any consistent conslusion, while eight of nine studies with respect to sick leave and two on disability pensions found AD to have a negative impact. Studies of change or loss of job and AD showed more diverse results, as not all studies documented a negative effect of AD on work life. Atopic dermatitis imposes a burden extending beyond personal, emotional and financial costs. This review strongly implies that AD affects sick leave, and though not fully clarified, possible also job choice, change or loss of job and even disability pensions for the more severe cases.

An exploratory, prospective, open-label trial of ingenol mebutate gel 0.05% for the treatment of external anogenital warts.

BACKGROUND: Anogenital warts (AGW) can cause physical discomfort and decreased quality of life. Recent case reports suggest that ingenol mebutate gel might be an effective treatment of AGW. OBJECTIVE: To explore primarily the safety, and secondarily the efficacy of ingenol mebutate gel 0.05% in patients with AGW. METHODS: This was an exploratory, open-label, 1-arm trial of ingenol mebutate gel 0.05% administered up to three times to patients with AGW. Safety was assessed by occurrence and severity of local skin reactions (LSRs) and treatment-related adverse events (AEs). Efficacy was assessed by complete clearance and reduction in AGW count 14 days after last treatment, and recurrence 12 weeks after clearance. RESULTS: Of 41 patients enrolled, 40 received treatment and 26 completed the trial. Patients had a median AGW count of 11.0 and AGW duration of 3.0 years at baseline. All patients experienced transient LSRs following treatment with a maximum composite LSR score of 7.5 (on a scale from 0 to 18). A total of 93% of patients reported treatment-related AEs, most frequently pain (85%) and procedural complications (35%) due to smearing of the gel. 78% of patients took mild analgesics for the pain, typically for 1-2 days following treatment. The majority of AEs were of moderate-to-severe intensity. Seventeen of 39 patients (43.6%) had complete clearance 14 days after last treatment, and AGW count was reduced by 90.9%. There was a tendency towards lower clearance rate in patients with longer duration of AGW. Eight of 14 patients (57.1%) had AGW recurrence 12 weeks after clearance. CONCLUSION: Ingenol mebutate gel was associated with a high number of AEs and withdrawals due to painful local and adjacent skin reactions. Furthermore, it showed promising efficacy in reducing AGW despite a difficult-to-treat population. Optimization of the formulation is warranted to improve the safety profile of the treatment.

Effectiveness and safety of secukinumab in 69 patients with moderate to severe plaque psoriasis: A retrospective multicenter study.

Secukinumab (anti-IL17A) is effective as treatment for moderate to severe plaque psoriasis, but real-life data on effectiveness and safety lack. We aimed to present real-life data of all Danish patients treated with secukinumab (n = 69). At baseline, before initiation of treatment with secukinumab 300 mg (47.8%) or off-label treatment with secukinumab 150 mg (52.2%), the median PASI score was 7.1. A total of 66.7% (34/51) and 52.9% (27/51) of patients still on secukinumab at week 12 achieved a PASI (Psoriasis Area and Severity Index)-50 and PASI-75 of 66.7% and 52.9%, respectively. A total of 83.0% (44/53) and 60.4% (32/53) of the patients had a PASI-score < 5 and PASI-score < 2, respectively, after 12 weeks on treatment with secukinumab. A third of the patients had secukinumab discontinued due to limited clinical improvement or adverse events (n = 23) within a median of 92 days (interquartile range 51-212 days). Notably, the majority of the patients may represent a particularly difficult-to-treat group of patients, as 92.8% had been refractory to other biologic treatment. A total of 26.1% (n = 18) experienced adverse events. Secukinumab appears to be an effective treatment option with a favorable side effect profile in patients with plaque psoriasis who are refractory to or have side effects of traditional biologic drugs.

Chronic urticaria in the real-life clinical practice setting in Sweden, Norway and Denmark: baseline results from the non-interventional multicentre AWARE study.

BACKGROUND: Chronic urticaria (CU) is characterized by the recurrence of itchy hives and/or angioedema for more than 6 weeks. AWARE (A World-wide Antihistamine-Refractory Chronic Urticaria Patient Evaluation) is a multinational study designed to document the real-life treatment situation, burden of disease and clinical resource usage of H1-antihistamine-refractory CU patients. OBJECTIVE: To examine baseline data from Scandinavian AWARE patients. METHODS: AWARE is a prospective, non-interventional, multinational, umbrella design study, which includes adults (≥18 years) with a confirmed CU diagnosis (>2 months) that is refractory to H1-antihistamines. Baseline patient characteristics, disease activity (urticaria control test [UCT]), pharmacological treatment, comorbidities and healthcare usage were documented by the treating physician. Quality of life (QoL; dermatology life quality index [DLQI]; chronic urticaria quality of life questionnaire [CU-Q2 oL; Danish patients only]) and work productivity and activity impairment (WPAI) scores were also assessed. RESULTS: Overall, 158 CU patients from seven centres in Denmark (n = 80), Norway (n = 50) and Sweden (n = 28) were included in this baseline analysis. Mean age and BMI were 40.3 years and 26.5 kg/m2 , respectively. The majority of patients were female (69.6%), had uncontrolled CU (75.6%; UCT score <12) and had a 'spontaneous' component to their CU (61.4% CSU; 20.3% both CSU and chronic inducible urticaria). Common comorbidities included asthma (19.6%), allergic rhinitis (16.5%) and food allergies (8.2%). Overall, 60.1% of patients reported using treatments for CU including non-sedative H1-antihistamines (40.5%), corticosteroids (19%), montelukast (14.6%) and omalizumab (8.2%). Pharmacological treatment rates increased to 96.2% during the baseline visit. On average, patient QoL was moderately affected (mean DLQI score 7.7) and healthcare resource usage was high. CONCLUSION: Adult Scandinavian H1-antihistamine-refractory CU patients reported high rates of healthcare usage and QoL impairment. Rates of pharmacological treatment use were low before study enrolment but increased to almost 100% during the baseline visit.

Transient hair loss in patients with chronic spontaneous urticaria treated with omalizumab.

SUMMARY: Omalizumab (anti-IgE) is used as add-on therapy for antihistamine refractory chronic urticaria patients. The most commonly reported adverse effects were headache, arthralgia, upper respiratory infections, fatigue, nausea and injection-site reactions. However, lately a few cases of hair loss have been reported. We describe a case of transient hair loss in a young female patient after initiating treatment with omalizumab. Despite this side effect, the patient continued with omalizumab treatment for 10 months with good effect.