Direct Comparison of Real-world Effectiveness of Biologics for Psoriasis using Absolute and Relative Psoriasis Area and Severity Index Scores in a Prospective Multicentre Cohort.

Real-world evidence, directly comparing the effectiveness of interleukin (IL)17-inhibitors, IL23-inhibitors, tumour necrosis factor alpha (TNF-α)-inhibitors and an IL12/23-inhibitor in psoriasis, is scarce. The aim of this study was to directly compare the first-year effectiveness of biologic therapies for psoriasis, corrected for confounders. This prospective, multicentre cohort study assessed BioCAPTURE data on etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab in 1,080 treatment episodes of 700 patients with psoriasis. The course of the mean absolute Psoriasis Area and Severity Index (PASI) and the proportion of patients who achieved PASI90/PASI75 were compared using linear mixed models and mixed logistic regression models respectively, corrected for baseline PASI, biologic naivety, and weight. Patients treated with adalimumab, ustekinumab, secukinumab, ixekizumab, or guselkumab all had a significantly lower mean PASI after 12 months compared with etanercept, and significantly higher overall odds of reaching PASI90 than those treated with etanercept. Patients treated with ixekizumab or guselkumab also had higher probabilities of reaching PASI90 than adalimumab, ustekinumab, and secukinumab. Relative to randomized controlled trials, the proportions of patients who reached PASI90/75 were lower in this real-world study.

Health Economic Consequences of a Tightly Controlled Dose Reduction Strategy for Adalimumab, Etanercept and Ustekinumab Compared with Standard Psoriasis Care: A Cost-utility Analysis of the CONDOR Study.

A dose reduction strategy for adalimumab, etanercept and ustekinumab in patients with psoriasis who have stable and low disease activity has recently been compared with usual care in the CONDOR study (CONtrolled DOse Reduction) of biologics in patients with psoriasis with low disease activity. The aim of the current study was to perform a cost-utility analysis with a 12-month time horizon alongside this trial, using prospectively measured healthcare costs and quality-adjusted life years, based on Short-Form Six-Dimension utilities. Bootstrap analys-es were used to calculate the decremental cost-utility ratio and the incremental net monetary benefit. The dose reduction strategy resulted in a mean cost saving of €3,820 (95th percentile -€3,099 to -€4,509) per patient over a period of 12 months. There was an 83% chance that dose reduction would result in a reduction in quality adjusted life years (mean -0.02 (95th percentile -0.06 to 0.02). In conclusion, dose reduction of biologics resulted in substantial cost savings with an acceptable reduction in quality of life.

Beliefs About Medicines in Patients with Psoriasis Treated with Methotrexate or Biologics: A Cross-sectional Survey Study.

Methotrexate (MTX) and biologics are frequently used treatments for psoriasis. Exploring patients' beliefs about their treatment may help to elucidate patients' attitudes towards these therapies. A cross-sectional survey was conducted using the Beliefs about Medicines Questionnaire-Specific (BMQ-Specific) in patients treated with methotrexate or biologics. BMQ-Specific scores (Necessity and Concerns scales) were calculated and patients were classified as "accepting", "indifferent", "ambivalent" or "sceptical" towards their treat-ment. Biologics users scored higher on the Necessity scale than did methotrexate users. Both groups had lower Concerns scores than Necessity scores. A high Necessity scale was associated with a low Psoriasis Area and Severity Index score in both groups and long treatment duration in the methotrexate group. Although this study cannot make a direct comparison, it was observed that most patients on biologics could be classified as "accepting" (59%), and most patients on MTX could be classified as "indifferent" (47%). In conclusion, the BMQ-Specific is useful to identify patients with a sceptical, ambivalent or indifferent profile. These profiles may negatively influence patient's attitude towards their medication.

Tight controlled dose reduction of biologics in psoriasis patients with low disease activity: a randomized pragmatic non-inferiority trial.

BACKGROUND: Psoriasis is an immune-mediated chronic inflammatory skin disorder for which several targeted biologic therapies became available in the last 10 years. Data from patients with rheumatoid arthritis revealed that dose tapering combined with tight control of disease activity is successful. For psoriasis patients the lowest effective dose of biologics needs to be determined. The objective was to assess whether dose tapering of biologics guided by Psoriasis Area and Severity Index (PASI) and Dermatology Quality of Life Index (DLQI) scores in psoriasis patients with controlled disease activity is non-inferior (NI) to usual care. METHODS/DESIGN: This is a multicenter, pragmatic, randomized, non-inferiority trial with cost- effectiveness analysis. One hundred and twenty patients with stable low disease activity (PASI ≤ 5 and DLQI ≤ 5) for at least 6 months with a stable use of adalimumab, etanercept or ustekinumab will be randomized 1:1 to the dose reduction group or usual care. In the dose reduction group, the treatment intervals will be prolonged stepwise, resulting in a 33% and 50% dose reduction, respectively. Disease activity is monitored every three months with PASI and DLQI. In case of flare the treatment is adjusted to the previous effective dose. The primary outcome (PASI) at 12 months will be analyzed with ANCOVA in which the baseline PASI will be included as covariate to gain efficiency. The secondary outcomes include number of and time to disease flares, health-related quality of life, serious adverse events, and costs. DISCUSSION: With this study we want to assess whether disease activity guided dose reduction of biologics can be achieved for psoriasis patients with low stable disease activity, without losing disease control. By using the lowest effective dose of biologics, we expect to minimize side effects and save costs. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov ( NCT 02602925 ). Trial registration date October 9 2015.

Tailored Therapist-Guided Internet-Based Cognitive Behavioral Treatment for Psoriasis: A Randomized Controlled Trial.

OBJECTIVE: Patients with somatic conditions, such as psoriasis, frequently suffer from high burden of their disease in daily life and might benefit from internet-based cognitive behavioral therapy (ICBT) tailored to their adjustment problems. The aim of this multicenter randomized controlled trial was to examine the effects of therapist-guided, individually tailored ICBT in a clinical sample of patients with psoriasis. METHODS: A total of 131 patients with psoriasis, who were screened for a psychological risk profile, were randomized to either care as usual (CAU, n = 66) or ICBT in addition to CAU (n = 65). Participants filled out standardized self-report questionnaires assessing physical and psychological functioning and impact on daily activities at baseline, posttreatment assessment, and 6-month follow-up. RESULTS: In covariate-controlled linear mixed-model analyses, significantly larger improvements in ICBT compared to CAU were found in the primary outcomes physical functioning (p = 0.03, d = 0.36) and impact on daily activities (p = 0.04, d = 0.35), but not in psychological functioning (p = 0.32), up to 6 months after treatment compared to baseline. In explorative analyses, the working alliance measured at the beginning of ICBT treatment predicted improved physical (p = 0.02) and psychological (p < 0.001) outcomes. CONCLUSIONS: Results underline the promise of therapist-guided, individually tailored ICBT to improve physical functioning and reduce the impact of psoriasis on daily activities in patients with a psychological risk profile. Establishing a good therapeutic relationship early on may be an important factor that influences treatment outcomes in personalized ICBT interventions. Further research is needed to evaluate ICBT effectiveness in additional samples and to explore its underlying mechanisms.

Effectiveness of Biologic and Conventional Systemic Therapies in Adults with Chronic Plaque Psoriasis in Daily Practice: A Systematic Review.

The efficacy of biologic or conventional systemic therapies for psoriasis has been shown in randomized controlled trials. Effectiveness, however, has been studied in daily practice cohorts, and no aggregation of effectiveness data is available. This systematic review searched PubMed and EMBASE and summarized the real-world evidence on effectiveness of biologics (adalimumab, etanercept, infliximab and ustekinumab) and conventional systemic therapies (acitretin, cyclosporine, fumarates and methotrexate) for the treatment of plaque psoriasis in adults. Thirty-two studies were included. Few data were available on infliximab, ustekinumab and conventional systemics. Results show that biologics and conventional systemics were effective in real-life treatment of psoriasis, with large ranges in the percentage of patients reaching 75% improvement in psoriasis area and severity index score compared with baseline, especially for etanercept and adalimumab treatment. Combination therapies of biologics with conventional systemics, and dose adjustments of biologics were frequently applied strategies and may explain the large range in improvements between cohorts.

Impairment in work and activities of daily life in patients with psoriasis: results of the prospective BioCAPTURE registry.

Background: Little is known about the extent of impairments in work and activities of daily life (ADL) in patients with psoriasis, and the influence of contextual factors such as disease-related characteristics and treatment. Therefore, this study aimed to assess these impairments in patients with psoriasis who started using biologicals/small molecule inhibitors.Methods: Using data from the prospective BioCAPTURE registry, we collected patient, disease, and treatment parameters, as well as work/ADL impairments at baseline, 6 and 12 months. Changes in impairment parameters and correlations between impairment and patient/disease characteristics were assessed using generalized estimating equations.Results: We included 194 patients in our analysis. After biological initiation, disease activity decreased significantly (PASI 11.2 at baseline versus 3.9 at 12 months, p < 0.001). Work-for-pay in this cohort was lower than in the Dutch general population (53% versus 67%, p = 0.01). In patients who had work-for-pay, presenteeism improved over time (5% at baseline versus 0% at 12 months, p = 0.04). Up to half of the patients reported impairments in ADL, which did not change over time. Associations between impairments and contextual factors varied, but all impairments were associated with worse mental/physical general functioning.Conclusion: Patients with psoriasis using biologicals are less likely to have work-for-pay. Treatment improves the work productivity of employed patients, but we were unable to detect changes in ADL performance.

Comparison of Tightly Controlled Dose Reduction of Biologics With Usual Care for Patients With Psoriasis: A Randomized Clinical Trial.

Importance: Biologics revolutionized the treatment of psoriasis. Biologics are given in a fixed dose, but lower doses might be possible. Objective: To investigate whether dose reduction (DR) of biologics in patients with stable psoriasis is noninferior to usual care (UC). Design, Setting, and Participants: This pragmatic, open-label, prospective, controlled, noninferiority randomized clinical trial was conducted from March 1, 2016, to July 22, 2018, at 6 dermatology departments in the Netherlands. A total of 120 patients with plaque psoriasis and stable low disease activity who were receiving treatment with adalimumab, etanercept, or ustekinumab were studied. Interventions: Patients were randomized 1:1 to DR (n = 60) or UC (n = 60). In the DR group, injection intervals were prolonged stepwise, leading to 67% and 50% of the original dose. Main Outcomes and Measures: The primary outcome was between-group difference in disease activity corrected for baseline at 12 months compared with the predefined noninferiority margin of 0.5. Secondary outcomes were Psoriasis Area and Severity Index (PASI) score and health-related quality of life (including Dermatology Life Quality Index [DLQI] and Medical Outcomes Study 36-Item Short Form Health Survey scores), proportion of patients with short and persistent flares (defined as PASI and/or DLQI scores >5 for ≥3 months), and proportion of patients with successful dose tapering. Results: Of 120 patients (mean [SD] age, 54.0 [13.2] years; 82 [68%] male), 2 patients were lost to follow-up, 2 patients had a protocol violation, and 5 patients had a protocol deviation, leaving 111 patients for the per-protocol analysis (53 in the DR group and 58 in the UC group). The median PASI scores at month 12 were 3.4 (interquartile range [IQR], 2.2-4.5) in the DR group and 2.1 (IQR, 0.6-3.6) in the UC group (mean difference, 1.2; 95% CI, 0.7-1.8). This indicates that noninferiority was not demonstrated for DR compared to UC. The median DLQI score at month 12 was 1.0 (IQR, 0.0-2.0) in the DR group and 0.0 (IQR, 0.0-2.0) in the UC group (mean difference, 0.8; 95% CI, 0.3-1.3), indicating noninferiority for DR compared with UC. No significant difference was found regarding persistent flares between groups (n = 5 in both groups). Twenty-eight patients (53%; 95% CI, 39%-67%) in the DR group tapered their dose successfully at 12 months. No severe adverse events related to the intervention occurred. Conclusions and Relevance: In this trial, noninferiority was not demonstrated for DR of adalimumab, etanercept, and ustekinumab based on the PASI in patients with psoriasis compared with UC with the chosen noninferiority margin. However, the strategy was noninferior based on the DLQI. Dose tapering did not lead to persistent flares or safety issues. Trial Registration: ClinicalTrials.gov Identifier: NCT02602925.

Systemic treatment of psoriatic patients with bexarotene decreases epidermal proliferation and parameters for inflammation, and improves differentiation in lesional skin.

BACKGROUND: Bexarotene, a novel synthetic retinoid X receptor (RXR)-selective retinoid, has been reported to have antiproliferative and apoptotic stimulating effects in cutaneous T-cell lymphoma. In benign, hyperproliferative, and retinoid sensitive disorders, such as psoriasis, bexarotene has not been evaluated so far and no information on these parameters is available. OBJECTIVE: In the present study, immunohistochemical parameters for proliferation, differentiation, inflammation, and apoptosis were investigated in a group of bexarotene-treated psoriatic patients. METHODS: Twenty-nine patients with plaque-type psoriasis were treated for 12 weeks with oral bexarotene in four dose-defined treatment panels. Treatment was initiated in the following consecutive order: 1.0 mg/kg/day, 2.0 mg/kg/day, 0.5 mg/kg/day, and 3.0 mg/kg/day. Biopsies for immunohistochemical analysis were taken at the baseline and after 12 weeks of treatment. RESULTS: Significant reductions in Ki-67, keratin 16, transglutaminase, dermal CD4, epidermal CD8, and inflammation scores were seen after bexarotene treatment in combination with a significant increase in keratin 10. No induction of keratin 13 and 19 and no alterations in apoptosis associated p53 expression were observed. Apart from a weak significant dose-response effect for Ki-67, no other significant dose-response effects were seen. CONCLUSION: We have demonstrated efficacy of oral bexarotene in psoriasis in doses up to 3.0 mg/kg/day during 12 weeks of treatment for proliferation, differentiation, and inflammation parameters. Studies investigating higher doses of bexarotene in a larger number of patients are necessary to reveal potentially dose-related immunohistochemical effects of this new rexinoid and to elucidate the role of RXR-signaling in retinoid-associated keratin expression.

Development and design of a multidisciplinary training program for outpatient children and adolescents with psoriasis and their parents.

INTRODUCTION: To describe and illustrate in a case-study design the development and design of a multidisciplinary training program for outpatient children and adolescents with psoriasis and their parents. METHODS: For the development of the program, a steering group was assembled, systematic semi-structured interviews were held and the literature was reviewed. RESULTS: Aim of the training program was to strengthen patients and their parents in coping with and diminishing psoriasis-related problems in an outpatient setting. The program included treatment modules of medical information and skin care, itch and scratch problems, psychological issues in coping with the psoriasis, sleep hygiene and relapse prevention. Descriptive results in the case patient showed improvement of all outcome variables in the expected direction. CONCLUSION: This is the first multidisciplinary training program for outpatient children and adolescents with psoriasis and their parents. It aims at improving coping skills and self-management and could be a promising addition to regular treatment.

Treatment of plaque psoriasis with the two-compound product calcipotriol/betamethasone dipropionate versus both monotherapies: an immunohistochemical study.

The combination of calcipotriol (Cp) and topical corticosteroids increases efficacy and reduces side effects as compared to monotherapies. Previous studies suggest that such combinations may have an added value with respect to reduction of T-cell subsets. A two-compound product consisting of Cp and betamethasone dipropionate (BD) has become available for the treatment of psoriasis and is clinically superior to both monotherapies. No immunohistochemical data are available on the in vivo effects of the two-compound formulation versus monotherapy with respect to the three key processes in psoriasis pathogenesis: epidermal proliferation, epidermal differentiation and inflammation. Therefore, 18 patients were treated with the two-compound product, Cp monotherapy or BD monotherapy for 6 weeks and biopsies were taken before and after 4 and 6 weeks of treatment. These biopsies were stained immunohistochemically and analysed (semi)quantitatively. All treatments decreased the number of Ki-67(+) cells and increased the keratin 15(+) staining. A more pronounced reduction of epidermal and dermal T-cell markers and human beta defensin-2 was seen following combination treatment, compared with both monotherapies. In conclusion, the investigated markers of the skin immune system and epidermal proliferation indicated an added value of the two-compound product over both monotherapies.

Effectiveness of a multidisciplinary itch-coping training programme in adults with atopic dermatitis.

The short- and longer-term effectiveness of a brief, multidisciplinary itch-coping group training scheme in adults with atopic dermatitis was evaluated. Clinical severity scores (Eczema Area and Severity Index) and validated self-report measures were obtained in a waiting-list control condition (n=30) and a treatment condition (n=61) at pre- and post-treatment and in the treatment condition at 3- and 12-month follow-ups. Relative to the control condition, all post-treatment measures showed improvements in terms of enhanced skin status, reduced itching and scratching and improved itch-coping patterns. In the treatment condition, the changes were sustained or further improved at both follow-ups. Also, the dermatological healthcare use was significantly reduced during the follow-up periods, in terms of fewer visits to the dermatologist and decreased use of topical corticosteroids and itch-relieving medication (histamine antagonists). The brief multidisciplinary itch-coping programme in adults with atopic dermatitis considerably reduced itch-scratching patterns, improved their skin status and reduced the use of dermatological care, both in the short and longer term.