Topical Cyperus rotundus essential oil for treatment of axillary hyperpigmentation: a randomized, double-blind, active- and placebo-controlled study.

BACKGROUND: The oil of the grass Cyperus rotundus (purple nutsedge) is an effective and safe treatment option for a variety of conditions. It has anti-inflammatory and antipigmenting properties. There have been no clinical trials comparing topical C. rotundus oil with skin-lightening treatments for axillary hyperpigmentation. AIM: To assess the efficacy of C. rotundus essential oil (CREO) in treating axillary hyperpigmentation, and compare with another active treatment hydroquinone (HQ) and a placebo (cold cream) in this study. METHODS: The study included 153 participants, who were assigned to one of three study groups: CREO, HQ group or placebo group. A tri-stimulus colorimeter was used to assess pigmentation and erythema. Two independent experts completed the Physician Global Assessment, and the patients completed a self-assessment questionnaire. RESULTS: CREO had significantly (P < 0.001) better depigmenting effects than HQ. CREO and HQ did not differ significantly in terms of depigmentation effects (P > 0.05); however, there were statistically significant differences in anti-inflammatory effects and decrease in hair growth (P < 0.05) in favour of CREO. CONCLUSIONS: CREO is a cost-effective and safe treatment for axillary hyperpigmentation.

Home-based narrowband UVB, topical corticosteroid or combination for children and adults with vitiligo: HI-Light Vitiligo three-arm RCT.

BACKGROUND: Systematic reviews suggest that narrowband ultraviolet B light combined with treatments such as topical corticosteroids may be more effective than monotherapy for vitiligo. OBJECTIVE: To explore the clinical effectiveness and cost-effectiveness of topical corticosteroid monotherapy compared with (1) hand-held narrowband ultraviolet B light monotherapy and (2) hand-held narrowband ultraviolet B light/topical corticosteroid combination treatment for localised vitiligo. DESIGN: Pragmatic, three-arm, randomised controlled trial with 9 months of treatment and a 12-month follow-up. SETTING: Sixteen UK hospitals - participants were recruited from primary and secondary care and the community. PARTICIPANTS: Adults and children (aged ≥ 5 years) with active non-segmental vitiligo affecting ≤ 10% of their body area. INTERVENTIONS: Topical corticosteroids [mometasone furoate 0.1% (Elocon®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) plus dummy narrowband ultraviolet B light]; narrowband ultraviolet B light (narrowband ultraviolet B light plus placebo topical corticosteroids); or combination (topical corticosteroids plus narrowband ultraviolet B light). Topical corticosteroids were applied once daily on alternate weeks and narrowband ultraviolet B light was administered every other day in escalating doses, with a dose adjustment for erythema. All treatments were home based. MAIN OUTCOME MEASURES: The primary outcome was self-assessed treatment success for a chosen target patch after 9 months of treatment ('a lot less noticeable' or 'no longer noticeable' on the Vitiligo Noticeability Scale). Secondary outcomes included blinded assessment of primary outcome and percentage repigmentation, onset and maintenance of treatment response, quality of life, side effects, treatment burden and cost-effectiveness (cost per additional successful treatment). RESULTS: In total, 517 participants were randomised (adults, n = 398; and children, n = 119; 52% male; 57% paler skin types I-III, 43% darker skin types IV-VI). At the end of 9 months of treatment, 370 (72%) participants provided primary outcome data. The median percentage of narrowband ultraviolet B light treatment-days (actual/allocated) was 81% for topical corticosteroids, 77% for narrowband ultraviolet B light and 74% for combination groups; and for ointment was 79% for topical corticosteroids, 83% for narrowband ultraviolet B light and 77% for combination. Target patch location was head and neck (31%), hands and feet (32%), and rest of the body (37%). Target patch treatment 'success' was 20 out of 119 (17%) for topical corticosteroids, 27 out of 123 (22%) for narrowband ultraviolet B light and 34 out of 128 (27%) for combination. Combination treatment was superior to topical corticosteroids (adjusted risk difference 10.9%, 95% confidence interval 1.0% to 20.9%; p = 0.032; number needed to treat = 10). Narrowband ultraviolet B light was not superior to topical corticosteroids (adjusted risk difference 5.2%, 95% confidence interval -4.4% to 14.9%; p = 0.290; number needed to treat = 19). The secondary outcomes supported the primary analysis. Quality of life did not differ between the groups. Participants who adhered to the interventions for > 75% of the expected treatment protocol were more likely to achieve treatment success. Over 40% of participants had lost treatment response after 1 year with no treatment. Grade 3 or 4 erythema was experienced by 62 participants (12%) (three of whom were using the dummy) and transient skin thinning by 13 participants (2.5%) (two of whom were using the placebo). We observed no serious adverse treatment effects. For combination treatment compared with topical corticosteroids, the unadjusted incremental cost-effectiveness ratio was £2328.56 (adjusted £1932) per additional successful treatment (from an NHS perspective). LIMITATIONS: Relatively high loss to follow-up limits the interpretation of the trial findings, especially during the post-intervention follow-up phase. CONCLUSION: Hand-held narrowband ultraviolet B light plus topical corticosteroid combination treatment is superior to topical corticosteroids alone for treatment of localised vitiligo. Combination treatment was relatively safe and well tolerated, but was effective in around one-quarter of participants only. Whether or not combination treatment is cost-effective depends on how much decision-makers are willing to pay for the benefits observed. FUTURE WORK: Development and testing of new vitiligo treatments with a greater treatment response and longer-lasting effects are needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17160087. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 64. See the NIHR Journals Library website for further project information.

The Home Interventions and Light therapy for the treatment of vitiligo (HI-Light Vitiligo) trial aimed to find out whether or not treating vitiligo at home with a narrowband ultraviolet B light, either by itself or with a steroid ointment, is better than treatment using a steroid ointment only. We enrolled 517 children (aged ≥ 5 years) and adults who had small, active (i.e. recently changing) patches of vitiligo into the study. Participants received one of three possible treatment options: steroid ointment (plus dummy light), hand-held narrowband ultraviolet B light therapy (plus placebo ointment) or both treatments used together. We asked participants to judge how noticeable their target vitiligo patch was after 9 months of treatment. We considered the treatment to be successful if the participants' responses were either 'a lot less noticeable' or 'no longer noticeable'. The results showed that using both treatments together was better than using a steroid ointment on its own. Around one-quarter of participants (27%) who used both treatments together said that their vitiligo was either 'no longer noticeable' or 'a lot less noticeable' after 9 months of treatment. This was compared with 17% of those using steroid ointment on its own and 22% of those using narrowband ultraviolet B light on its own. All treatments were able to stop the vitiligo from spreading. Patches on the hands and feet were less likely to respond to treatment than patches on other parts of the body. The trial found that the vitiligo tended to return once treatments were stopped, so ongoing intermittent treatment may be needed to maintain the treatment response. The treatments were found to be relatively safe and easy to use, but light treatment required a considerable time commitment (approximately 20 minutes per session, two or three times per week). This trial showed that using steroid ointment and narrowband ultraviolet B light together is likely to be better than steroid ointment alone for people with small patches of vitiligo. Steroid ointment alone can still be effective for some people and remains a useful treatment that is able to stop vitiligo from spreading. The challenge is to make hand-held narrowband ultraviolet B light treatment available as normal care in the NHS for people with vitiligo.

Treatment of Medicare Patients with Moderate-to-Severe Psoriasis who Cannot Afford Biologics or Apremilast.

Elderly patients are a group with a high frequency of psoriasis. Their disease burden has negative impacts on their quality of life. While there is a clear need to treat these patients, there are challenges in doing so. This work seeks to define the challenges that exist in treating elderly Medicare patients, as well as to provide treatment suggestions for providers to follow if they encounter one or more of these challenges. Providers face the following challenges when creating treatment plants for elderly patients with psoriasis: difficulty in obtaining drug coverage through Medicare, increased medical comorbidities, and polypharmacy. Providers aim for regimens that are affordable, safe, and efficacious, but it is not always clear how to achieve this combination, especially in elderly Medicare patients. This work is relevant in that it aims to explain the logistical roadblocks posed by Medicare coverage and provide solutions for commonly encountered issues in the treatment of a disabling and common disease in a high-risk population. Specifically, alternative treatment options to biologics and small-molecule inhibitors are discussed and include topical therapies, phototherapy, methotrexate, acitretin, and cyclosporine and for psoriatic arthritis include corticosteroids and leflunomide. The specific risks and benefits of these therapies in the elderly population are provided, allowing providers to make patient-specific decisions about optimal regimens.

Decision-Analytic Modeling for Time-Effectiveness of the Sequence of Induction Treatments for Moderate to Severe Plaque Psoriasis.

Importance: Systemic psoriasis treatments vary in efficacy and cost but also in time until onset of action. Patients with no response to a first induction treatment are typically switched to another, and some patients require several treatments before they see an improvement. Objective: To determine the most cost-effective sequence of induction treatment through a comparative time-effectiveness analysis of different systemic treatment sequences currently licensed in Germany for moderate to severe plaque psoriasis. Design, Setting, and Participants: This time-effectiveness analysis used a decision-analytic model set in the German health care system. The population simulated to receive the treatment sequences consisted of adult men and women with psoriasis vulgaris or plaque type psoriasis eligible for systemic treatment. Systematic reviews were performed to generate model input values. Data were collected from November 1 through December 15, 2017, and analyzed from January through August 2018. Interventions: Five treatment sequences frequently used in Germany, identified through an online expert survey (response rate, 10 of 15 [66.7%]), and 4 theoretical sequences starting with a biological agent. Treatments included methotrexate sodium (MTX), cyclosporine (CSA), fumaric acid esters (FAE), adalimumab (ADA), ixekizumab (IXE), infliximab (INF), and secukinumab (SEC). Main Outcomes and Measures: Two health states were defined: responder (patients achieving a Psoriasis Area Severity Index [PASI] ≥75) and nonresponder (PASI <75). Probability values were defined as response rates of PASI-75. Treatment effects were determined by the mean change in Dermatology Life Quality Index (DLQI) score. Time until onset of action was assessed as weeks until 25% of patients reach PASI-75. Individual time-effectiveness ratios were calculated per treatment sequence as time until onset of action (in weeks) per minimally important difference (MID) in DLQI and were subsequently ranked. Results: Treatment sequences starting with a biological agent, including IXE-INF-SEC (1.4 weeks per DLQI-MID), INF-IXE-SEC (2.05 weeks per DLQI-MID), SEC-IXE-ADA (2.1 weeks per DLQI-MID), and ADA-IXE-SEC (2.8 weeks per DLQI-MID) were more time-effective than frequently used treatment sequences, including MTX-SEC-ADA (6.8 weeks per DLQI-MID), MTX-ADA-IXE (7.0 weeks per DLQI-MID), MTX-ADA-SEC (7.2 weeks per DLQI-MID), MTX-FAE-ADA (10.05 weeks per DLQI-MID), and FAE-MTX-CSA (11.5 weeks per DLQI-MID). The results were robust to deterministic sensitivity analyses. Conclusions and Relevance: When allocating monetary resources, policy makers and regulators may want to consider time until patients experience an MID in their quality of life as an additional outcome measure. Trial Registration: PROSPERO Identifier: CRD42017074218.

Economic burden and productivity loss related to eczema: A prevalence-based follow-up study in Vietnam.

OBJECTIVE: Eczema, a chronic dermatologic disease, has been recognized as an economic burden in publications all over the word but only minimally as such in Vietnam. The aim of this prospective study was to quantify the financial hardships and impairments suffered by eczema patients. METHODS: This cross-sectional prevalence-based study involved 136 patients, whose conditions were classified into three severity levels on the basis of the medications that they were prescribed. Prescription therapy was administered for a month, after which there was patient-oriented assessment of effectiveness. The work productivity and activity impairment (WPAI) questionnaire was used to evaluate productivity loss, which was expressed in percentage form. Bootstrapping was conducted to determine continuous variables and demographybased differences in cost values among the patient groups. RESULTS: For the month-long treatment, each eczema patient needed an average of US$68.1 (range: US$56.2- US$81.5) with the highest proportion being spent on cosmetic treatments. There is noticeable difference between groups among which patients' symptoms demonstrated in distinct levels. The estimates indicated that eczema resulted in 27.8% and 23.1% impairments in work and daily activities, respectively. CONCLUSIONS: The aggravation of disease symptoms can increase the direct costs borne by eczema patients. A decrease in productivity, which is one of the most serious consequences of the condition, should be paid adequate attention to minimize burdens to society.

Drug Survival of Biological Therapies for Psoriasis Treatment in Germany and Associated Costs: A Retrospective Claims Database Analysis.

INTRODUCTION: Our aim was to study drug survival and associated costs of biologic treatment in a German real-world cohort of biologic-naïve psoriasis patients. METHODS: We utilized a German claims database base with 3,682,561 enrolled patients between 2001 and 2015. Kaplan-Meier curves were plotted to show the persistence of different biologics. To determine factors that influence persistence, a Cox regression analysis was performed. In addition, associated costs were calculated 12 months before and after treatment start with biologics. RESULTS: Among 75,561 patients with a diagnosis of psoriasis, we identified 347 patients who received a biologic; 176 of them were biologic-naïve prior to initiating therapy. Overall, the 1-year persistence rate was 56%. The highest persistence rate was observed for ustekinumab (80%). Younger patients, and those with a high comorbidity index, had a numerically increased risk of treatment discontinuation. However, parameter values were not statistically significant. While the overall costs after treatment start increased due to the acquisition costs of biologics, we found a strong decrease (- 41%) in sick leave after treatment with biologics had been initiated. CONCLUSION: Observed drug survival rates in this real-world setting were relatively low. In line with previous studies, ustekinumab had a higher persistence rate than other biologics. FUNDING: Janssen-Cilag.

Effectiveness, safety, and economic evaluation of topical application of a herbal ointment, Jaungo, for radiation dermatitis after breast conserving surgery in patients with breast cancer (GREEN study): Study protocol for a randomized controlled trial.

INTRODUCTION: This is a prospective, open-label, parallel-group, randomized controlled trial that evaluates the effectiveness and safety of adjuvant application of Jaungo (JUG) for radiation-induced dermatitis (RD) in breast cancer patients undergoing radiation therapy, in comparison with general supportive care (GSC). METHODS/DESIGN: Eighty female patients, who have been diagnosed with unilateral breast cancer, will be allocated to either the JUG or GSC group with an allocation ratio of 1:1 after breast conservation surgery, in the Kyung Hee University Korean Medicine Hospital, Seoul, Republic of Korea. Both the groups will be subjected to GSC, but only the JUG group participants will apply adjuvant JUG ointment on the irradiated skin for 6 weeks, twice a day. The primary outcome of this study is the assessment of incidence rate of RD using the Radiation Therapy Oncology Group (RTOG) for toxicity gradation of 2 or more. Maximum pain level, quality of life, adverse reactions, and pharmacoeconomic evaluations will also be included. DISCUSSION: The primary outcome will be statistically compared using the logrank test after estimating the survival curve using the Kaplan-Meier method. Continuous variables will be tested using independent t test or Mann-Whitney U test. The adverse events will be evaluated with Chi-square or Fisher exact test. All the data will be analyzed at a significance level of 0.05 (two-sided) with R software (The R Foundation). TRIAL REGISTRATION: CRIS (Clinical Research Information Service), KCT0003506, 14 February 2019.

A Cost-utility Analysis of Calcipotriol/Betamethasone Dipropionate Aerosol Foam versus Ointment for the Topical Treatment of Psoriasis Vulgaris in Sweden.

Psoriasis is a chronic inflammatory disorder that imposes a substantial economic burden. We conducted a cost-utility analysis from a Swedish healthcare payers perspective using a decision-tree model with a 12-week time horizon. Patients with psoriasis vulgaris could have two 4-week cycles of topical treatment with calcipotriol 50 µg/g and betamethasone 0.5 mg/g as dipropionate (Cal/BD) foam or Cal/BD ointment before progressing to phototherapy/methotrexate. In the base-case analysis, Cal/BD foam dominated over Cal/BD ointment. The increased efficacy of Cal/BD foam resulted in fewer consultations and a decreased risk of progressing to phototherapy/methotrexate. Although Cal/BD foam costs more than Cal/BD ointment, this was offset by lower costs for phototherapy/methotrexate or consultation visits. Sensitivity analyses revealed that the base-case net monetary benefit was robust to plausible variations in key parameters. In conclusion, Cal/BD foam was predicted to be more cost-effective than Cal/BD ointment in the treatment of psoriasis vulgaris.

Brodalumab for the Treatment of Moderate-to-Severe Plaque Psoriasis: An Evidence Review Group Evaluation of a NICE Single Technology Appraisal.

As part of the National Institute for Health and Care Excellence single technology appraisal process, brodalumab was assessed to determine the clinical and cost effectiveness of its use in the treatment of moderate-to-severe plaque psoriasis. The Centre for Reviews and Dissemination and the Centre for Health Economics Technology Assessment Group at the University of York were commissioned to act as the independent Evidence Review Group. This article provides a summary of the Evidence Review Group's review of the company's submission, the Evidence Review Group report and the National Institute for Health and Care Excellence Appraisal Committee's subsequent guidance issued in March 2018. The main clinical effectiveness data were derived from three well-conducted, multicentre, double-blind randomised controlled trials. The trials demonstrated that brodalumab statistically significantly reduced the severity of psoriasis and its impact on health-related quality of life, compared with placebo, at 12 weeks. In comparison with ustekinumab, statistically significantly more patients taking brodalumab had reduced psoriasis severity at 12 weeks. Psoriasis severity and quality of life also appeared improved at 52 weeks, although statistical significance was not assessed. Withdrawal rates were comparable to drug survival rates of other biological therapies and rates of adverse events were similar between brodalumab and ustekinumab. A network meta-analysis was presented, comparing brodalumab with other therapies available at the same point in the treatment pathway (i.e. in patients for whom standard systemic therapy or phototherapy is inadequately effective, not tolerated or contraindicated). The network meta-analysis ranked treatments in order of effectiveness, in terms of achieving different levels of Psoriasis Area and Severity Index response. The results indicated that brodalumab had a similar probability of response to ixekizumab, secukinumab and infliximab and a higher probability of response than ustekinumab, adalimumab, etanercept, apremilast, dimethyl fumarate and placebo. The company's economic model compared nine treatment sequences that included three lines of active therapy, consisting of brodalumab and other comparators recommended by the National Institute for Health and Care Excellence, followed by best supportive care. The sequence with brodalumab in the first-line position dominated sequences that started with adalimumab, infliximab, secukinumab and ustekinumab. The incremental cost-effectiveness ratio of the brodalumab sequence compared to less effective and non-dominated sequences ranged from £7145 (vs. the etanercept sequence) to £13,353 (vs. the dimethyl fumarate sequence) per quality-adjusted life-year gained. The incremental cost-effectiveness ratio for the more costly and effective ixekizumab sequence was £894,010 per quality-adjusted life-year gained compared to the brodalumab sequence. At a threshold of £20,000 per quality-adjusted life-year gained, the brodalumab sequence had the highest probability of being cost effective (96%). The main limitation of the company's economic model was the restrictive nature of the sequences compared. Twelve separate scenarios based on key uncertainties were explored by the Evidence Review Group. The only scenarios where brodalumab was ranked lower than first were not considered to be more appropriate or plausible than the assumptions or scenarios included in the company's base case. The treatment rankings identified in the Evidence Review Group's alternative base case were identical to those derived from the company's base case model. At the first National Institute for Health and Care Excellence Appraisal Committee meeting, the Committee concluded that brodalumab appears to be as effective as other anti-interleukin-17 agents and is cost effective, based on the discount agreed in the patient access scheme. Brodalumab is recommended as an option for treating adults with severe plaque psoriasis (defined by a total Psoriasis Area and Severity Index score of 10 or more and a Dermatology Life Quality Index score of more than 10) who have not responded to other systemic non-biological therapies. Brodalumab should be stopped at 12 weeks if the psoriasis has not responded adequately.

Out-of-pocket Costs for Individuals with Atopic Eczema: A Cross-sectional Study in Nine European Countries.

Atopic eczema (AE) is one of the most common non-communicable inflammatory skin diseases, and has a huge socioeconomic impact. Studies on the everyday economic impact of AE on patients, however, are limited. To estimate the annual extra out-of-pocket spending due to AE among patients in Europe, a cross-sectional study using computer-assisted phone interviewing of patients with AE was performed in 9 European countries. A total of 1,189 patients (56% women) with AE, who were either eligible for, or on, systemic treatment, participated in the study between October 2017 and March 2018. Mean extra spending on everyday necessities was €927 per patient per year for healthcare expenses, and this figure was slightly, but not statistically significantly, influenced by the severity of AE. Emollients and moisturizers accounted for the highest monthly costs, followed by medication that was not reimbursed, doctors' and hospital costs. AE-related out-of-pocket costs pose a substantial burden for affected individuals, are higher than in other chronic diseases, and should always be included in economic assessments of the impact of this disease.

Cost-Effectiveness of Targeted Pharmacotherapy for Moderate to Severe Plaque Psoriasis.

BACKGROUND: Newer classes of targeted drugs for moderate to severe plaque psoriasis are more effective and more expensive than older classes, posing a difficult and potentially costly decision about whether to use them as initial targeted treatments. OBJECTIVE: To estimate the clinical and economic outcomes of initial targeted treatment for the following drugs: adalimumab, etanercept, and infliximab (TNFα inhibitors); apremilast (PDE4 inhibitor); ustekinumab (IL-12/23 inhibitor); and ixekizumab, secukinumab, and brodalumab (IL-17 inhibitors). METHODS: We developed a Markov model to simulate patient outcomes as measured by quality-adjusted life-years (QALYs) and health care costs over a 10-year period. We assumed that patients who fail initial targeted treatment either proceed to subsequent therapy or discontinue targeted treatment. Effectiveness estimates for initial treatment were defined as improvement in Psoriasis Area and Severity Index (PASI) from baseline and derived from a 2018 network meta-analysis. Wholesale acquisition drug costs were discounted by a class-specific, empirically derived rebate percentage off of 2016 costs. We conducted one-way and probabilistic sensitivity analyses to assess uncertainty in results. RESULTS: The incremental benefits compared with no targeted treatment were, in descending order: ixekizumab 1.68 QALYs (95% credible range [CR] = 1.11-2.02), brodalumab 1.64 QALYs (95% CR = 1.08-1.98), secukinumab 1.51 QALYs (95% CR = 1.00-1.83), ustekinumab 1.43 QALYs (95% CR=0.94-1.74), infliximab 1.27 QALYs (95% CR = 0.89-1.55), adalimumab 1.15 QALYs (95% CR = 0.76-1.44), etanercept 0.97 QALYs (95% CR = 0.61-1.25), and apremilast 0.87 QALYs (95% CR = 0.52-1.17). Costs of care without targeted treatment totaled $66,451, and costs of targeted treatment ranged from $137,080 (apremilast) to $255,422 (ustekinumab). Probabilistic sensitivity analysis results indicated that infliximab and apremilast are likely to be the most cost-effective initial treatments at willingness-to-pay thresholds around $100,000 per QALY, while IL-17 drugs are more likely to be cost-effective at thresholds approaching $150,000 per QALY. Acquisition cost of the initial targeted drug and utility of clinical response were the most influential parameters. CONCLUSIONS: Our findings suggest that initial targeted treatment with IL-17 inhibitors is the most effective treatment strategy for plaque psoriasis patients who have failed methotrexate and phototherapy. Apremilast, brodalumab, infliximab, ixekizumab, and secukinumab are cost-effective at different willingness-to-pay thresholds. Additional research is needed on whether the effectiveness of targeted agents changes when used after previously targeted agents. DISCLOSURES: Funding for this study was contributed by the Institute for Clinical and Economic Review (ICER). Ollendorf, Chapman, Pearson, and Kumar are current employees, and Loos and Liu are former employees, of ICER, an independent organization that evaluates the evidence on the value of health care interventions, which is funded by grants from the Laura and John Arnold Foundation, Blue Shield of California Foundation, and the California HealthCare Foundation. ICER's annual policy summit is supported by dues from Aetna, AHIP, Anthem, Alnylam, AstraZeneca, Blue Shield of California, Cambia Health Solutions and MedSavvy, CVS Caremark, Editas, Express Scripts, Genentech, GlaxoSmithKline, Harvard Pilgrim Health Care, Health Care Service Corporation, OmedaRx, United Healthcare, Johnson & Johnson, Kaiser Permanente, Premera Blue Cross, Merck, National Pharmaceutical Council, Takeda, Pfizer, Novartis, Lilly, Humana, Prime Therapeutics, Sanofi, and Spark Therapeutics. Linder owns stock in Amgen, Biogen, and Eli Lilly; has contingent value rights in Sanofi Genzyme (related to alemtuzumab for multiple sclerosis); has received grant support from Astellas Pharma not related to this study and Clintrex, which was supported by AstraZeneca on an unrelated topic; and has received an honorarium from the Society of Healthcare Epidemiology of America (SHEA) as part of the SHEA Antimicrobial Stewardship Research Workshop Planning Committee, an educational activity supported by Merck. No other authors have potential conflicts of interest.

Persistence rates and medical costs of biological therapies for psoriasis treatment in Japan: a real-world data study using a claims database.

BACKGROUND: Biological therapies (BTs) including infliximab (IFX), adalimumab (ADL), secukinumab (SCK) and ustekinumab (UST) are approved in Japan for the treatment of psoriasis. Although the persistence rates and medical costs of BTs treatment have been investigated in multiple foreign studies in recent years, few such studies have been conducted in Japan and the differences between patients who adhered to treatment and those who did not have not been reported. This study is aimed at investigating the persistence rates and medical costs of BTs in the treatment of psoriasis in Japan, using the real-world data from a large-scale claims database. METHODS: Claims data from the JMDC database (August 2009 to December 2016) were used for this analysis. Patient data were extracted using the ICD10 code for psoriasis and claims records of BT injections. Twelve-month and 24-month persistence rates of BTs were estimated by Kaplan-Meier methodology, and 12-month-medical costs before and after BT initiation were compared between persistent and non-persistent patient groups at 12 months. RESULTS: A total of 205 psoriasis patients treated with BTs (BT-naïve patients: 177) were identified. The 12-month/24-month persistence rates for ADL, IFX, SCK, and UST in BT-naïve patients were 46.8% ± 16.6%/46.8 ± 16.6%, 53.0% ± 14.9%/41.0% ± 15.5%, 55.4%/55.4% (95% CI not available) and 79.4% ± 9.9%/71.9% ± 12.2%, respectively. Statistically significant differences in persistence were found among different BT treatments, and UST was found to have the highest persistence rate. The total medical costs during the 12 months after BT initiation in BT-naïve patients were (in 1000 Japanese Yen): 2218 for ADL, 3409 for IFX, 465 for SCK, 2824 for UST (average: 2828). Compared with the 12-month persistent patient group, the total medical costs in the persistent group was higher (Δ:+ 118), but for some medications such as IFX or UST cost increases were lower for persistent patients. CONCLUSIONS: UST was found to have the highest persistence rate among all BTs for psoriasis treatment in Japan. The 12-month medical costs after BT initiation in the persistent patient group may not have increased as much as in the non-persistent patient group for some medications.

Topical treatment utilization for patients with atopic dermatitis in the United States, and budget impact analysis of crisaborole ointment, 2.

BACKGROUND: Atopic dermatitis (AD), a chronic inflammatory skin disease, is often treated with topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI). Crisaborole ointment is a non-steroidal, phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate AD. In December 2016, crisaborole was approved in the US for mild-to-moderate AD in patients ≥2 years of age. AIMS: To evaluate real-world utilization and cost of TCS and TCI in the US and estimate the budget impact of crisaborole over 2 years from a third-party payer perspective. METHODS: TCS and TCI prescriptions in 2015 for patients ≥2 years of age with ≥1 AD diagnosis in the Truven Health Analytics MarketScan Commercial and Medicare Supplemental Research Databases were analyzed for patients receiving TCI or TCS alone or in combination (TCS/TCI population) and patients receiving TCI alone or in combination with TCS (TCI population). A budget impact model used TCS and TCI market shares, annual use, and cost per prescription. Crisaborole uptake rates of 4.7% (TCS) and 20.2% (TCI), with an annual increase of 1% in year 2, were assumed. Budget impact was calculated as total and per-member-per-month (PMPM) cost over 2 years for a health plan of 1 million members. RESULTS: Annual prescriptions/patient ranged from 1.36-6.41; annual cost/patient was $53-$1,465. The budget impact of crisaborole over 2 years in the TCS/TCI population was $350,946 (PMPM, $0.015), with increases of $162,106 in year 1 (PMPM, $0.014) and $188,841 in year 2 (PMPM, $0.016). The budget impact in the TCI population was -$22,871, with decreases of $11,160 in year 1 and $11,712 in year 2 (each PMPM, -$0.001). For both populations, one-way sensitivity analyses showed that budget impact was most sensitive to changes in crisaborole cost and annual use. CONCLUSIONS: From US payer perspectives, adoption of crisaborole results in modest pharmacy budget impact/savings.

Cost-effectiveness of secukinumab as first biologic treatment, compared with other biologics, for moderate to severe psoriasis in Germany.

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin 17A, has demonstrated strong and sustained efficacy in adults with moderate to severe psoriasis in clinical trials. OBJECTIVE: This analysis compared the cost per responder of secukinumab as first biologic treatment of moderate to severe psoriasis, with adalimumab, infliximab, etanercept and ustekinumab in Germany. METHODS: A 52-week decision-tree model was developed. Response to treatment was assessed based on the likelihood of achieving a predefined Psoriasis Area and Severity Index (PASI) response to separate the cohort into responders (PASI ≥75), partial responders (PASI 50 to 74) and non-responders (PASI <50). Responders at week 16 continued initial treatment, whereas partial responders and non-responders were switched to standard of care, which included methotrexate, cyclosporine, phototherapy and topical corticosteroids. Sustained response was defined as 16-week response maintained at week 52. A German healthcare system perspective was adopted. Clinical efficacy data were obtained from a mixed-treatment comparison; 2016 resource unit costs from national sources; and adverse events and discontinuation rates from the literature. We calculated cost per PASI 90 responder over week 16 and week 52, as well as cost per sustained responder between weeks 16 and 52. RESULTS: Secukinumab had the lowest cost per PASI 90 responder over 16 weeks (€18 026) compared with ustekinumab (€18 080), adalimumab (€23 499), infliximab (€29 599) and etanercept (€34 037). Over 52 weeks, costs per PASI 90 responder ranged from €42 409 (secukinumab) to €70 363 (etanercept). Likewise, secukinumab had the lowest cost per sustained 52-week PASI 90 responder (€22 690) compared with other biologic treatments. Sensitivity analyses, excluding patient copayments, showed similar results. CONCLUSIONS: First biologic treatment with secukinumab for moderate to severe psoriasis is cost-effective, with lowest cost per responder compared with other biologic treatments in Germany.

Implementation of Instrument Based on Eight Health Related Quality of Life Domains for Measuring of Willingness to Pay for Psoriasis Treatment.

BACKGROUND: Psoriasis vulgaris (PsV) is a chronic skin condition that has a major impact on health-related quality of life (HRQOL). AIM: To determine the individual burden of PsV on HRQOL using willingness to pay (WTP) instrument. MATERIALS AND METHODS: Fifty-one consecutive PsV patients were asked to evaluate their overall health and psoriasis affected health by visual analogue scale (VAS), and interviewed on 8 domains (physical, emotional, sleep, work, social, self-care, intimacy, and concentration) of HRQOL and WTP for a hypothetical cure in each domain. Two additional questions proposing 6 alternatives for therapy were also asked. The analysis is performed with descriptive and frequency statistics, Mann-Whitney and Kruskal-Wallis tests. RESULTS: The domains ranked highly were: physical comfort (90%), social comfort (77%), emotional health (75%) and work (53%). The following tendencies concerning WTP for top four impacted domains were found: the median WTP were the highest in the top impacted domains; the younger patients were willing to pay more than the older ones; the highest median WTP amounts appear in the lowest income group; the highest median WTP is associated with smaller psoriasis affected health VAS scores. The largest proportion and number of patients (37.3%, n=19) stated preferences for the systemic therapy. The second preferred choice was the thalassotherapy (29.4%, n=15). CONCLUSIONS: The utility and reliability of the instrument based on the assessment of WTP stated preferences for 8 domains of HRQOL for evaluation the individual burden of psoriasis were strongly supported.

The cost-effectiveness of blue-light therapy in the treatment of mild-to-moderate psoriasis.

AIM: To investigate the cost-effectiveness of blue-light therapy versus a two-compound formulation (TCF) (Dovobet® gel [calcipotriol and betamethasone]) in mild-to-moderate psoriasis. METHODS: A Markov model was applied to describe the course of disease among Dutch patients with a Psoriasis Area and Severity Index (PASI) score ≤ 10 over a 52-week time horizon. Patients received either 12-week blue-light therapy or two 4-week treatments with TCF. Patients, experiencing no PASI reduction after either therapy, were assumed to receive 12-week ultraviolet B phototherapy. RESULTS: There was no significant difference in PASI reduction between two interventions (71 vs 72%). However, blue-light therapy was associated with a cost savings of EU€248. CONCLUSION: Treatment of mild-to-moderate chronic plaque psoriasis using blue-light therapy may be more cost-effective than TCF.

[Treatment of psoriasis: before and now]. / Behandling av psoriasis: från tjära till biologiska läkemedel - Terapiarsenalen har förändrats dramatiskt ­ nya läkemedel kan ge helt läkt hud till fler patienter.

Treatment of psoriasis: before and now  Psoriasis is a multisystem inflammatory disease primarily affecting the skin. Despite its prevalence and considerable effect on quality of life, psoriasis is still underdiagnosed and undertreated. Many patients seek initial evaluation and treatment at primary care level and therefore it is important to know that treatment of psoriasis has advanced tremendously in recent years. Decisions on psoriasis management should be based on assessment of disease severity and phenotype, the existence of physical and psychological comorbidities, the need for referral to dermatologist for specialist care, the patient's preferences and, when possible, identification and elimination of psoriasis trigger factors. Individual treatment goals should be agreed with the patient and treatment should aim to achieve these goals. An individualized, patient centered approach based on the potential of current treatments and a good interpersonal communication between patient and doctor, is essential for effective management of psoriasis.

Treatment adherence and beliefs about medicines among Egyptian vitiligo patients.

Vitiligo is a chronic disorder of depigmentation that has different treatment modalities, but patients' nonadherence is common. This study aimed to assess the influence of patients' medication beliefs on patients' adherence to topical, oral medications, and phototherapy in vitiligo. Between September 2015 and February 2016, 260 patients with vitiligo were asked to fill in the Beliefs about Medicines Questionnaire (BMQ) to assess their beliefs about therapy for vitiligo. Their adherence to the therapy was examined using the 8-item Morisky Medication Adherence Scale (MMAS-8). RESULTS: The MMAS-8 scale and BMQ had good internal consistency (Cronbach's α = 0.78 and 0.66, respectively). Using Morisky's recommended cutoff point, 71% of patients were categorized as low or nonadherent to the scheduled therapy. Patients who perceived specific necessity of dermatological medicines significantly adhered to their therapy (OR 1.23; 95% CI 1.09, 1.38; p = 0.001) whereas patients who had specific concerns about the adverse effects exhibited significant low adherence (OR 0.65; 95% CI 0.56, 0.76; p < 0.001). CONCLUSION: Positive beliefs about the necessity of medications in vitiligo do not necessarily reflect high adherence. Patients' adherence behavior is a multidimensional and dynamic process. The prolonged course of treatment, its cost, and unsatisfactory outcomes influenced the patients' adherence.

Health economic analyses of psoriasis management: a systematic literature search.

In the course of the chronic skin disease psoriasis, where a variety of treatment interventions is available, a strong growth of health economic studies comparing treatment costs and benefits can be noticed. The objective was to identify health economic evaluations of psoriasis treatments that have been published to date. Of particular interest were the mostly used analysis and outcome parameters, the compared treatments, and the question, if available health economic studies may be used to perform a meta-analysis of qualitative findings. A systematic literature search using PubMed Medline, Ovid Medline, and Cochrane Library was performed for articles, published and available until mid of January 2016. Among the key words were the terms "psoriasis" and "cost-effectiveness". The search resulted in 318 articles without duplicates. Thereof 60 health economic analyses in psoriasis management were identified. Most of these are cost-effectiveness evaluations (45). The clinical parameter PASI (Psoriasis Area Severity Index) is the most often used cost-effectiveness outcome (33) followed by the Dermatology Life Quality Index (DLQI) (6). In case of cost-utility analyses, QALYs (quality-adjusted life-years) were mostly generated with the help of EuroQol five dimensions questionnaire (EQ-5D) (12), which was partly based on PASI and DLQI values. The majority of health economic studies is focusing on the direct medical and non-medical costs without consideration of productivity losses. Almost 70 % of 60 publications were conducted in Europe. Overall, most considered systemic treatments were the biological agents etanercept (36), adalimumab (27), and infliximab (26) followed by ustekinumab (17) and phototherapy (incl. UV-B, PUVA/psoralen combined with UV-A) (14). Comparisons including only topical treatments mostly focused on vitamin D treatment (14), corticosteroids (13), and coal tar products (6) followed by dithranol (5) and tazarotene (4). Given the setting, compared treatments, and study conditions, different results can be found for medical decision-making. Thereby, it can be noted that there are no standards on methods and outcomes measures available. This leads to a very limited comparability of health economic studies and presents no comfortable basis to examine a meta-analysis of health economic results. The presented systematic review shows the need for nationwide data and interpretation.

Retrospective analysis of the effectiveness and costs of traditional treatments for moderate-to-severe psoriasis: A single-center, Italian study.

BACKGROUND: Current guidelines recommend the use of systemic therapy and phototherapy for the treatment of moderate-to-severe plaque psoriasis. OBJECTIVES: To evaluate the effectiveness, impact on health status perception, and costs of traditional systemic therapies and phototherapy in real-life patients with moderate-to-severe psoriasis. METHODS: Retrospective analysis of data from 100 psoriatic patients referring to a dermatology clinic in Italy and treated with traditional therapies. RESULTS: Patients were predominantly treated with cyclosporine (72%). Cyclosporine was associated with fewer treatment discontinuations due to lack of efficacy (37%) compared with methotrexate (65%), acitretin (67%) and phototherapy (50%). Rates of treatment discontinuation due to adverse events were: cyclosporine (24%), methotrexate (9%), acitretin (25%) and phototherapy (0%). Improvements in PASI scores were comparable between treatments. The need for topical therapy was reduced with cyclosporine versus other therapies (35% vs 71%, p = 0.0009); respectively, 33% of patients treated with cyclosporine versus 14% of patients receiving other therapies perceived an improvement in their health status (p = 0.0018). Mean total per-patient direct costs of the first treatment cycle were higher with cyclosporine than with other therapies (€1812.85 vs €648.90, p < 0.0001). CONCLUSIONS: Cyclosporine was effective even if more expensive than other traditional therapies. Nevertheless patients' perception of improvement was quite low.