Oral Psoriasis Treatment Adherence and Intervention Study

Psoriasis is a common, chronic inflammatory disease that has a major impact on patients'
quality of life. Patients' response to treatment is variable. Poor adherence to topical, oral
and biologic psoriasis treatments is common and may account for poor responses.1, 2 Many
psoriasis patients do not even fill their prescriptions.3 Electronic monitoring of adherence
provides the most detailed and accurate way to assess adherence. While studies using
electronic monitors have assessed adherence to topical psoriasis treatments and to biologics,
adherence to oral psoriasis treatments is not as well characterized. Understanding adherence
to oral psoriasis treatments is critical, as the therapeutic windows for these treatments are
narrower than for other psoriasis treatment options, making adherence to recommended dosing
all the more critical.

Developing methods to improve psoriasis patients' adherence has the potential to provide an
immediate, practical means to improve patients' treatment outcomes. Return visits improve
patients' use of medication & treatment outcomes but are not practical and add additional
costs to the patient and medical system. Having patients report on their treatment experience
without an office visit offers promise for improving adherence but has not been tested in a
psoriasis population.

The primary hypothesis of the investigators study is that adherence to oral psoriasis
treatment is poor and that a reporting intervention may improve adherence to oral psoriasis
treatment.

The Specific Aims of this study are:

1. To determine adherence to oral psoriasis treatments (methotrexate) with electronic
monitors.

2. To assess the relationship between adherence and psoriasis outcomes (measured by body
surface area [BSA], Physician Global Assessment [PGA] and [BSA]x[PGA]).

3. To identify factors that are associated with adherence to oral psoriasis treatment,
including physician trust, confidence in the treatment plan, and depression which will
be measured with the Wake Forest University Physician Trust Scale (WFUPTS),4-6 the
Treatment Satisfaction Questionnaire for Medication (TSQM),7 and the Hamilton Depression
Rating Scale (HAM-D).

4. To test obtain preliminary data on the impact of an Internet-reporting measure on
patients' adherence to oral psoriasis treatment.

The investigators propose an investigator-blinded, 6-month prospective study of 40 patients
aged 12 and older who have been prescribed oral psoriasis treatment. Adherence will be
assessed using Medication Event Monitoring System (MEMS®) caps, electronic monitors affixed
to the medication containers. Investigators and subjects will be blinded to the adherence
data until the final (Month 6) treatment visit.

This study is of high significance, providing critically important information on how
patients use oral psoriasis treatments, as well as a foundation to develop and implement
intervention trials to improve adherence and outcomes in patients treated with oral psoriasis
treatments. Innovations in this study include seeking to change the paradigm of the
investigators understanding of the role of adherence in oral psoriasis treatment, including
effects on treatment failures and side effects, developing a new understanding of the roles
of physician and medication trust in adherence, and potentially changing the timing and
methods of clinical assessments in psoriasis (and other) patients in light of the effects of
the timing and methods of clinical assessments on treatment adherence and outcomes. The use
of objective electronic adherence monitors and well-validated assessment tools adds strength
to the approach of this study; another strength of the approach is careful attention to
research ethics of adherence monitoring. The environment of this study is particularly
strong, with facilities for and extensive experience in all aspects of adherence monitoring
research.

The overall goal of this study is to better understand and improve adherence behaviors in
patients with psoriasis, a common, chronic, relapsing, inflammatory disease. Psoriasis
reduces patients' quality of life, yet patients with psoriasis, as with other chronic
diseases, frequently misuse medicine, impairing effectiveness of prescribed therapies (when
underused) and increasing the risks of treatment (when overused or mistimed).8 Poor adherence
to treatment can be misconstrued as poor response, which can lead to unnecessary treatment
escalation resulting in exposing patients to more toxic or costly medications.9 In many
cases, non-adherence, rather than non-response, is the underlying precursor of treatment
failure.10, 11

Adherence issues with oral psoriasis treatment are largely unexplored and are of critical
importance. Oral methotrexate is widely used (encouraged by payors), yet it is risky, with a
more narrow therapeutic window than biologics. Other oral agents approved for psoriasis
include cyclosporine (with a risk of renal disease) and apremilast (which is associated with
gastrointestinal tolerability issues). While large database studies find that oral psoriasis
treatment is underused, the variation in use of oral psoriasis treatments among patients is
critically important and has not been defined.

Traditional methods for measuring medical adherence tend to be unreliable. Assessment methods
such as patient interviews, questionnaires, surveys, and diaries deliver inconsistent data
that depend upon the patient's willingness to accurately record medication use and ability to
remember what they did. Electronic monitoring devices offer an effective means for objective
adherence monitoring. Medication Event Monitoring System caps (MEMS®, AARDEX Corp., Fremont,
CA) include microprocessors in the bottle cap of a standard medication bottle that record
each time and date the bottle is opened and the interval since the last bottle opening.12

The availability of accurate electronic adherence measurement provides a foundation to study
novel ways to improve adherence. In several studies of psoriasis and other inflammatory skin
diseases, a clear pattern of improved adherence around the time of office visits is evident.
The tendency for patients to be more adherent around the time of office visits may be a form
of a more general tendency to be adherent when interacting with the healthcare system to
assess their treatment outcomes, a form of "white coat compliance" or Hawthorne effect. A
pilot study of adolescents with acne vulgaris tested whether adherence to topical benzoyl
peroxide could be improved by weekly online-reporting of their treatment experience.

Inclusion Criteria:

- Any male or female 12 years or older of age with a diagnosis of psoriasis who is
prescribed methotrexate by a dermatologist will be eligible for participation.

- Greater than 10% of body surface involvement for psoriasis.

- Subject is capable of understanding and willing to provide a signed and dated written
voluntary informed consent before any protocol specific procedures are performed.

- The subject is able to complete the study and comply with study instructions,
including attending all study visits.

Exclusion Criteria:

- Individuals younger than 12 years of age.

- Known allergy or sensitivity to methotrexate.

- Inability to complete all study-related visits, or inability to complete the Internet
survey due to inadequate Internet access.

- Introduction of any other prescription medication, topical or systemic, for psoriasis
while participating in the study.