Improvement of Psoriasis Patients' Adherence to Topical Drugs
Condition: Psoriasis Vulgaris
MeSH terms: Psoriasis
Study type: Interventional

Summary: 
      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) and quality of life.

      If the intervention can reduce the severity of psoriasis in a significant manner, there is a
      potential for a national implementation of the intervention.
    

Detailed description: 
      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, and 3) improve adherence to prescribed topical drugs.

      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.

      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=100).

      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.

      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, 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.
    

Intervention name(s): Improved support by health-care professionals
Intervention type(s): Other
Intervention description(s): Improved support to patients prescribed topical antipsoriatic drugs
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Supportive Care