INTRODUCTION
Psoriasis is a common, debilitating, immune-mediated disease; plaque psoriasis is the most common form, characterized
by thickened, erythemato-squamous plaques.1 First-line treatment of mild to moderate plaque psoriasis involves
topical therapies including corticosteroids and vitamin D analogs.2 However, as local and systemic adverse effects (AEs) can limit the use of topical therapies,3 additional treatment options
that are effective and well-tolerated are needed.
Janus kinase (JAK) intracellular signaling has been implicated in the pathogenesis of psoriasis.4 Tofacitinib (CP-690,550) is a small-molecule JAK inhibitor being investigated for the topical and oral treatment of plaque psoriasis. When the clinical trial in this report was conducted, the potential therapeutic benefits
of JAK inhibition in psoriasis had been demonstrated in a
Phase 1 study of oral tofacitinib administered over 14 days.5 A proof-of-concept pilot study was designed to evaluate efficacy, safety, local tolerability, and pharmacokinetics of a topical tofacitinib
solution in patients with chronic plaque psoriasis.
Proof-of-concept studies with topical formulations can be challenging;
relatively few patients are enrolled and only a small surface area is typically treated, potentially restricting the generation
of clinically meaningful results. The intra-subject design
(also termed half body, left-right, or bilateral design) utilizes each patient as his/her own control to reduce the impact of variability between patients. However, few studies have been published on this strategy’s limitations. The outcomes reported here have implications for future intra-subject studies of investigational
topical therapies.
MATERIALS AND METHODS
This study was performed in compliance with the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice guidelines. The study protocol was approved
by the institutional review board or independent ethics committee at each investigational center; all patients provided written, informed consent.
Study Design and Treatment
This was a Phase 2a, multicenter, randomized, double-blind, vehicle-controlled, eight-arm, parallel-group study (A3921038; ClinicalTrials.gov, NCT00678561) conducted at five centers in Canada and 13 centers in the United States between October 13, 2008 and July 24, 2009. The study employed a left-right, intra-subject design, whereby in each patient one psoriasis target plaque was randomly assigned to be treated with tofacitinib
solution, and one with vehicle. For each patient, matched