Dermatologist Preferences for Treatments to Compare in Future Randomized Controlled Comparative Effectiveness Trials for Moderate to Severe Psoriasis FREE

Approximately 1.2 million Americans have moderate to severe psoriasis, a chronic, inflammatory disease of the skin and joints that has substantial impact on health-related quality of life and is associated with excess cardiovascular risk and mortality.¹ Despite the rapid growth of treatments for psoriasis, insufficient data exist to distinguish between first- and second-line therapies. Thus, as emphasized by the Institute of Medicine,² there exists a critical need for comparative effectiveness research (CER) in psoriasis treatment. Since a crucial component of CER is to identify the priorities of stakeholders such as physicians, we conducted a study to describe US dermatologists' preferences for which treatments to compare in future randomized controlled trials (RCTs) in moderate to severe psoriasis.

We surveyed 1000 US dermatologists (500 National Psoriasis Foundation [NPF] members and 500 American Academy of Dermatology [AAD] members who self-reported that they treat psoriasis) as part of a larger study on preferences for psoriasis therapy. Dermatologists were asked to select 3 treatments they would most like to compare in an RCT for moderate to severe psoriasis from a list of 10 US Food and Drug Administration (FDA)–approved biological and oral systemic treatments and phototherapies (Figure 1). The order of treatment listings was randomized in 6 ways to reduce bias. Detailed data on the survey methods have been published elsewhere.^3- 4 The study was approved by the University of Pennsylvania institutional review board and conducted from May to August 2010.

The primary outcome was dermatologists' preferences for treatments to compare in an RCT, as indicated by each treatment's cumulative frequency of first, second, or third choice selection. Preferences were summarized descriptively and compared with respect to major provider characteristics.

We received questionnaire responses from 387 dermatologists (39% response rate). Responding dermatologists were mostly male (72%), NPF members (64%), and private practitioners (70%). Respondents were similar to nonrespondents with respect to sex, duration of practice, and geographic region. Additional data on respondents' baseline characteristics have been previously described.⁴ Of note, respondents indicated that a median of 90% of their patients with psoriasis being treated with systemic medications or phototherapy also concurrently used topical agents by prescription.

The treatments dermatologists most wanted to compare in an RCT were etanercept (58.7% [95% CI, 53.6%-63.6%]), adalimumab (50.9% [95% CI, 45.8%-56.0%]), ustekinumab (50.1% [95% CI, 45.0%-55.2%]), and methotrexate (45.5% [95% CI, 40.4%-50.6%]) (Figure 2). When preferences were stratified by provider characteristics, including sex, NPF vs AAD membership, geographic region, duration of practice, practice type, patient volume, and infusion center affiliation, the top 4 overall treatments remained the same, although the order of treatments within the top 4 occasionally differed. The presence of phototherapy units in the practice affected the degree of preference for including UV-B phototherapy in CER trials: 34.1% (95% CI, 28.3%-40.3%) of dermatologists with phototherapy units vs 14.6% (95% CI, 8.9%-22.1%) of dermatologists without phototherapy units selected UV-B therapy. However, the top 4 overall treatments were the same regardless of phototherapy availability.

Our results indicate that US dermatologists who treat psoriasis prefer to compare the newer subcutaneously administered tumor necrosis factor inhibitors and interleukin-12/23 inhibitor and the traditional oral systemic methotrexate in future CER trials. Etanercept, adalimumab, and ustekinumab gained FDA approval for plaque psoriasis in 2004, 2008, and 2009, respectively. Methotrexate, however, has been widely used since its approval in 1972.

Notably, our research group⁴ had previously observed that UV-B was the most preferred first-line treatment by dermatologists who treat psoriasis, followed by etanercept, adalimumab, and methotrexate, while UV-B was only the fifth most requested treatment for RCT inclusion among these providers. Ustekinumab, on the other hand, was the third most requested treatment to include in CER trials but was ranked as only the sixth most preferred first-line treatment for moderate to severe psoriasis.⁴

Our results also indicate that the concurrent use of prescription topical agents with systemic or phototherapy is common, but most RCTs have prohibited combination therapy.⁵ Thus, for CER trials to reflect real-world practice, permitting the concomitant use of topical prescription therapy should be considered.

Our findings are highly informative for future trial design because they represent the priorities of hundreds of US dermatologists who actively treat patients with psoriasis. Future studies should examine the priorities of other stakeholders, such as payers and patients, and other elements of CER trial design, such as primary efficacy outcomes, safety end points on which to discriminate, and treatment duration.