Improvement of Psoriasis Patients' Adherence to Topical Drugs

Study Overview
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Brief Summary
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Psoriasis affects 2-4% of the Western adult population and is a socio-economic burden for patients and society. Topical drugs are recommended as first-line treatment for mild-to-moderate psoriasis, but low adherence is a barrier for treatment success. There is a need for improved patient support for psoriasis patients, which is suggested to improve long-term use of topical drugs. The project aims to test whether a patient-supporting intervention delivered by healthcare professionals can improve the use of topical drugs. The intervention design is based on experiences with previous adherence-improving studies consisting of digital support by conducting a systematic literature search and holding focus groups with patients as well as healthcare professionals. The intervention consists of shared decision-making with patients, nurses and doctors, frequent consultations, easy access to healthcare professionals through video or in-office consultations and holding patients accountable for taking the medication. The intervention will be tested in a randomized controlled trial: during a 48 week period, a group of patients (18-85 years of age) diagnosed with mild-to-moderate psoriasis and treated with topical drugs will be randomized to an intervention (n=40) or non-intervention group (n=40). The primary outcome will be severity of psoriasis and secondary outcomes primary adherence (i.e., rate of filled prescriptions), quality of life and cost-effectiveness. If the intervention can reduce the severity of psoriasis in a significant manner and is cost-effective, there is a potential for a national implementation of the intervention.

Detailed Description
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Background Psoriasis is a chronic inflammatory skin disease affecting 2-4% of the Western adult population. It is associated with many comorbidities, negatively affects quality of life and is a socioeconomic burden for patients and society. Topical drugs are the recommended first-line treatment for mild-to-moderate psoriasis, but adherence rates are low, which is a barrier for treatment success, resulting in a need for systemic or biological treatments, which are associated with more severe adverse events and are more expensive than topical drugs. However, improved adherence to topical drugs is associated with improved efficacy. That is why there is a need for improving psoriasis patients' adherence to topical drugs. As a supplement to the introduction of new and advanced technology, there is a need for more studies on how to optimize the available healthcare professionals in dermatology clinics. Since dermatologists are a limited resource, there is a need to study how other healthcare professionals, e.g., hospital nurses and pharmaconomists at the pharmacies, can support psoriasis patients in their use of topical drugs. Hypothesis A patient-supporting intervention delivered by dermatologists, dermatology nurses and pharmaconomists significantly reduces psoriasis patients' severity of psoriasis compared to standard patient support. Aims The aim of the project is to test whether an individualized patient-supporting intervention delivered to psoriasis patients by dermatologists, nurses and pharmaconomists at a dermatology hospital clinic can: 1) reduce the severity of psoriasis, 2) improve quality of life, 3) improve adherence to prescribed topical drugs, and 4) be cost-effective compared to standard treatment. Ethical considerations All participants will be fully informed of the purpose of the study, and the study will be performed in accordance with the ethical principles in the Belmont report. Materials and methods The study is an investigator-initiated, single-centre, assessor-blinded, parallel group superiority randomized clinical study. Before inclusion of study participants, the study will be approved by the local regional ethics committee. We will include patients (18-85 years of age) with milder-to-moderate psoriasis. Outcomes Outcome measurements will be either patient-reported or assessor-blinded. Adherence measurements Primary adherence: Proportion of filled topical prescriptions. Secondary adherence: Amount of medication used according to weight of the remains in the used medication packages. Data will be assessed week 48. Disease severity measurements Disease severity will be measured by Lattice-System Physician's Global Assessment (LS-PGA) (15), and the quality of life will be measured by the Dermatology Life Quality Index (DLQI). This data will be assessed at baseline, weeks 12, 24, 36 and 48. Financial savings from use of the intervention The cost-analysis of optimized patient support will be measured by total use of psoriasis medication including topical treatments, systemic treatments, phototherapy and biological treatments compared to the cost of the intervention. A cost-utility analysis will be applied. Recruitment Psoriasis patients who use topical treatments and are referred to the Department of Dermatology at Odense University Hospital will be recruited to the project until there is a sufficient number of participants included (n=80). If needed, recruitment advertisement will be used. Hypothesis and expected number of participants Our null hypothesis is that there is no difference in reduction of psoriasis between the intervention and non-intervention groups. The sample size was calculated based on data from a previous project with consumption data for the use of prescribed calcipotriol betamethasone dipropionate cutaneous foam over 4 weeks. We expect an 20% difference in the LS-PGA, power 80%, two-sided significance of 95%, allocation of 1: 1 and an expected dropout rate of 25%. When using an unpaired t-test, the calculation resulted in the inclusion of a sample size consisting of 80 participants. Blinding and randomization Blinding of the data assessors: When the data assessor obtains baseline data from the study participants, it will be entered by an electronic data collection tool. Participants will be allocated 1: 1 to an intervention or non-intervention arm via a computer-generated block randomization. The data assessor will be blinded to the allocation. Statistics Analysis of the primary outcome: changes in LS-PGA Changes in LS-PGA measurements from baseline to weeks 12 and from baseline to weeks 24, 36 and 48 will be compared between the two groups by linear mixed model for longitudinal data. LS-PGA will be presented in box plots. As a sensitivity analysis on LS-PGA, the analysis will be carried out excluding missing data and after 100 times multiple imputations by multivariate normal regression on LS-PGA data, without included covariates in addition to with an imputation including treatment, age, sex and smoking as covariates. Analysis of secondary outcomes: Changes in DLQI and adherence Changes in DLQI measurements from baseline to weeks 12, 24, 36 and 48 will be compared between the two groups by linear mixed model for longitudinal data. DLQI will be presented in box plots. For the analysis of adherence (by filled prescriptions, weight and patient reported), we will dichotomize adherence rate with a selected cut-off of 80%, with adherence rates above 80% considered adherent (a cut-off typically used when studying adherence in chronic diseases) [7, 42]. We will compare the dichotomized adherences by using logistic regression. The statistical analysis will be conducted by an experienced statistician blinded to the intervention. An interim analysis is not planned. Economic analysis Costs will be presented as a total average cost totaling costs for psoriasis treatment distributed on hospital costs, primary health care costs, and pharmaceutical costs. The costs will be distributed on average total healthcare cost per patient in the non-intervention and intervention group. For cost-effectiveness analysis, average healthcare costs will be summarized per group as total costs across all trajectories and divided by the total number of participants in each group. The incremental cost-effectiveness ratio (ICER) for reduction in LS-PGA and DLQI will be calculated by dividing the mean cost difference between the groups measured by the difference in reduction of LS-PGA and DLQI from baseline to week 48. Dominance in the results exists if one strategy is found to be both cheaper and more effective. It will improve quality of the analysis, if the ICER reflects a minimal clinically importance difference (MCID) in the DLQI and LS-PGA (that is, at least a two-point difference in the DLQI as well as the LS-PGA). A trial-based economic evaluation of the cost-effectiveness of the intervention and standard care compared to standard care is planned. Main outcomes will be cost effectiveness based on incremental cost per reduction in LS-PGA and cost-utility based on incremental cost per reduction in DLQI. Changes in total cost of treatment from a two-year period up until study inclusion to the 48-week treatment period will be compared between the two groups. Discussion This study will demonstrate whether an individualized, optimized patient support delivered by doctors, nurses and pharmaconomists to dermatological patients can optimize the use of topical treatment, reduce the severity of psoriasis and have socioeconomic benefits compared to standard treatment. If the study shows that individualized and optimized patient support is effective and has economic benefits, it is intended for the intervention to be implemented in the clinic. In addition, we will work on implementing the intervention nationally by a translational process. Results from the study may also be referred to other chronic dermatological disorders. The study may be used methodically as a model for additional research projects investigating medical adherence in other chronic skin diseases.

Official Title
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Long-term Improvement of Psoriasis Patients' Adherence to Topical Drugs: Testing a Patient-supporting Intervention Delivered by Healthcare Professionals

Conditions
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Psoriasis Vulgaris

Intervention / Treatment
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* Other: Improved support by health-care professionals


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Legally competent patients with milder-to-moderate psoriasis Exclusion Criteria: Incapable patients not diagnosed with psoriasis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Intervention group: All participants will be instructed how to use of the medication according to the fingertip unit for topical steroids. All participants will be prescribed topical drugs based on shared decision between the prescriber and patient. The topical drugs will be either moderate corticosteroids (clobetasone-17-butyrate or hydrocortisone-17-butyrate), potent corticosteroids (betamethasone-17-valerate and betamethasone, mometasone furoate, fluocinolone acetonide or fluocinonide), very potent corticosteroids (clobetasol propionate), corticosteroids with antimicrobials (betamethasone and clioquinol, betamethasone and fusidic acid or fluocinolone acetonide and clioquinol), corticosteroid with calcipotriol or calcipotriol cream. During the study period, a nurse or pharmaconomist will deliver; Improved support and instructions to the patients Patients will receive a diary and access to more consultations. | Other: Improved support by health-care professionals<br>* Improved support to patients prescribed topical antipsoriatic drugs<br>|
| No Intervention: Non-intervention group<br>All participants will be instructed how to use of the medication according to the fingertip unit for topical steroids. All participants will be prescribed topical drugs based on shared decision between the prescriber and patient. The topical drugs will be either moderate corticosteroids (clobetasone-17-butyrate or hydrocortisone-17-butyrate), potent corticosteroids (betamethasone-17-valerate and betamethasone, mometasone furoate, fluocinolone acetonide or fluocinonide), very potent corticosteroids (clobetasol propionate), corticosteroids with antimicrobials (betamethasone and clioquinol, betamethasone and fusidic acid or fluocinolone acetonide and clioquinol), corticosteroid with calcipotriol or calcipotriol cream. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of psoriasis | Lattice-System Physician's Global Assessment (LS-PGA) (interval scale). From value 1 (no visible psoriasis) to 8 (severely affected by psoriasis). | Baseline and weeks 12, 24, 36 and 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary adherence | Proportion of expected consumed amount of topical drugs | Week 48 | 
| Primary adherence | Proportion of redeemed prescriptions | week 48 | 
| Quality of Life (QOL) | Daily Life Quality Index (DLQI) (interval scale). From value 0 (no impact on quality of life) to 30 (severe impact on quality of life). | Baseline and weeks 12, 24, 36 and 48 | 
| Cost of treatment | Total cost of antipsoriatic medication (incl. topical drugs, systemic drugs, phototherapy and biologics) during the last year | Baseline and week 48 | 
| European Quality of life 5 Dimensions (EQ-5D) (interval scale). | European Quality of life 5 Dimensions (EQ-5D) (interval scale). From value 0 (no impact on quality of life) to 1 (death). | Baseline and week 48 |