Meghan A. Feely, MD; Barry L. Smith, MD; Jeffrey M. Weinberg, MD
From the Department of Dermatology, Mount Sinai St. Luke’s-Roosevelt and Beth Israel Medical Centers of the Icahn School of Medicine at Mount Sinai, New York, New York.
Drs. Feely and Smith report no conflict of interest. Dr. Weinberg is a speaker and investigator for LEO Pharma.
This article is the first of a 3-part series. The second part will appear in May 2015.
Correspondence: Meghan A. Feely, MD, Department of Dermatology, Icahn School of Medicine at Mount Sinai, Mount Sinai St. Luke’s-Roosevelt, 1090 Amsterdam Ave, Ste 11B, New York, NY 10025 (mfeely@chpnet.org).
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.
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.
References
Topical therapies are a mainstay in the management of patients with mild to moderate psoriasis (Figure). Presently, US Food and Drug Administration–approved topical medications that are commercially available for use in patients with psoriasis include corticosteroids, vitamin D3 analogues, calcineurin inhibitors, retinoids, anthralin, and tar-based formulations.1 In recent years, research has furthered our understanding of the molecular mechanisms underlying the pathogenesis of psoriasis and has afforded the development of more targeted therapies. Novel topical medications currently in phase 2 and phase 3 clinical trials are discussed in this article, and a summary is provided in the Table.
Well-demarcated, salmon-colored, circular and polycyclic, thin plaques with micaceous scale on the back of a patient with mild to moderate psoriasis.
AN2728 (Phosphodiesterase 4 Inhibitor)
AN2728 (Anacor Pharmaceuticals, Inc) is a phosphodiesterase 4 inhibitor that blocks the inactivation of cyclic adenosine monophosphate, resulting in decreased production of inflammatory cytokines (eg, IL-6, IL-12, IL-23, tumor necrosis factor α [TNF-α]).2,3 In a randomized, double-blind, phase 2 clinical trial (N=35), 40% of patients treated with AN2728 ointment 5% reported improvement of more than 2 points in overall target plaque severity score versus 6% of patients treated with vehicle. In another randomized, double-blind, dose-response trial of 145 patients, those treated with AN2728 ointment 2% twice daily reported a 60% improvement versus 40% improvement in those treated with AN2728 ointment 0.5% once daily.3 In total, 3 phase 1 trials (registered at www.clinicaltrials.gov with the identifiers NCT01258088, NCT00762658, NCT00763204) and 4 phase 2 trials (NCT01029405, NCT00755196, NCT00759161, NCT01300052) have been completed; results were not available at the time of publication.
