Novel Psoriasis Therapies and Patient Outcomes, Part 1: Topical Medications
In recent years, advances in our understanding of inflammatory mediators and the underlying pathogenesis of psoriasis and psoriatic arthritis have shed light on potential therapeutic targets, which has led to the development of several new promising treatments. In this article, key clinical trials, mechanisms of action, patient outcomes, and relevant safety information for these novel topical medications will be evaluated. This article is the first in a 3-part series on treatments presently in the pipeline for the management of psoriasis and psoriatic arthritis including topical agents, biologic treatments, and systemic therapies in phase 2 and phase 3 clinical trials. With novel approaches to the disease process, these therapies may afford more targeted individualized treatment regimens and offer hope to patients with psoriasis and psoriatic arthritis who have reported a suboptimal therapeutic response to conventional therapies.
Practice Points
- Topical therapies are the cornerstone of treating patients with mild to moderate psoriasis. Commercially available medications approved by the US Food and Drug Administration for use in patients with psoriasis include corticosteroids, vitamin D3 analogues, calcineurin inhibitors, retinoids, anthralin, and tar-based formulations.
- Recent developments in our understanding of inflammatory mediators and the underlying pathogenesis of psoriasis have revealed new potential therapeutic targets, leading to the discovery of many promising treatments.
- Novel topical therapies currently in phase 2 and phase 3 clinical trials for patients with mild to moderate psoriasis may offer hope to patients who have reported a suboptimal therapeutic response to conventional treatments.
AS101 (Integrin Inhibitor)
AS101 (BioMAS Ltd), or ammonium trichloro (dioxoethylene-o,o') tellurate, acts as stimulator of regulatory T cells and a redox modulator inhibiting the leukocyte integrins α4β1 and α4β7 that enable CD4+ T-cell and macrophage extravasation; it also limits expression of the inflammatory cytokines IL-6 and IL-17.4 A randomized, placebo-controlled, double-blind, phase 2 study evaluating the efficacy of AS101 cream 4% twice daily for 12 weeks was withdrawn prior to enrollment (NCT00788424).
Tofacitinib (Janus Kinase 1 and 3 Inhibitor)
Tofacitinib (formerly known as CP-690,550)(Pfizer Inc) is a selective Janus kinase (Jak) 1 and Jak3 inhibitor that limits expression of cytokines that promote inflammation (eg, IFN-γ) and inhibits helper T cells (TH17) by downregulating expression of the IL-23 receptor. Epidermal keratinocyte proliferation in psoriasis is activated by TH17 cells that release IL-17 as well as TH1 cells that release IFN-γ and tumor necrosis factor. A phase 2a trial showed statistically significant improvement from baseline in the target plaque severity score for tofacitinib ointment 2% (least squares mean, −54.4%) versus vehicle (least squares mean, −41.5%).5 Two other phase 2 trials (NCT01246583, NCT00678561) assessing the efficacy, safety, tolerability, and pharmacokinetics of tofacitinib ointment in patients with mild to moderate psoriasis have been completed; results were not available at the time of publication. A phase 2b study that compared 2 dose strengths of tofacitinib ointment—10 mg/g and 20 mg/g—versus placebo over a 12-week period also was completed (NCT01831466); results were not available at the time of publication.
CT327 (Tyrosine Kinase Inhibitor)
CT327 (Creabilis SA) is a tyrosine kinase A (TrkA) inhibitor that affords a novel perspective in the treatment of pruritus by shifting the focus to sensory neurons. In a phase 2b study of 160 patients, a 60% change in the visual analog scale was noted at 8 weeks in the treatment group versus 21% in the placebo group.6 Two other phase 2 studies have been completed, one with a cream formulation of pegylated K252a (NCT00995969) and another with an ointment formulation (NCT01465282); results were not available at the time of publication.
DPS-101 (Vitamin D Analogue)
DPS-101 (Dermipsor Ltd) is a combination of calcipotriol and niacinamide. Calcipotriol is a vitamin D3 analogue that increases IL-10 expression while decreasing IL-8 expression.7 It curbs epidermal keratinocyte proliferation by limiting the expression of polo-like kinase 2 and early growth response-1.8 It also may induce keratinocyte apoptosis.9 Niacinamide is the amide of vitamin B3 and inhibits proinflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-8.10 In a dose-response phase 2b trial of 168 patients, DPS-101 demonstrated better results than either calcipotriol or niacinamide alone.11
IDP-118 (Proprietary Steroid and Retinoid Combination)
IDP-118 (Valeant Pharmaceuticals International, Inc) is a combination of halobetasol propionate (HP) 0.01% (a topical corticosteroid) and tazar-otene 0.045% (a selective topical retinoid) in a lotion formulation. In isolation, tazarotene is as effective as a mid to highly potent corticosteroid, but irritation may limit its tolerability. The use of combination treatments of mid to highly potent corticosteroids and tazarotene has shown enhanced tolerability and therapeutic efficacy.12 Ongoing studies include a phase 1 trial and a phase 2 trial to evaluate low- and high-strength preparations of IDP-118, respectively (NCT01670513). Another phase 2 trial evaluating the efficacy and safety of IDP-118 lotion (HP 0.01% and tazarotene 0.045%) versus IDP-118 monad HP 0.01% lotion, IDP-118 monad tazar-otene 0.045% lotion, and placebo has been completed (NCT02045277); results were not available at the time of publication.
Ruxolitinib (Jak1 and Jak2 Inhibitor)
Ruxolitinib (formerly known as INCB18424)(Incyte Corporation) is a selective Jak1 and Jak2 inhibitor. A phase 2 trial of ruxolitinib showed a 53% decline in the score for mean total lesions in patients treated with ruxolitinib phosphate cream 1% (P=.033) versus 54% in those treated with ruxolitinib phosphate cream 1.5% (P=.056) and 32% in those treated with placebo.13 Three other phase 2 studies (NCT00617994, NCT00820950, NCT00778700) have been completed; results were not available at the time of publication.
