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Novel therapies for psoriasis.

Cather J1, Menter A.

Author information

Abstract

The T cell-driven immunopathogenesis of psoriasis has been well recognized since cyclosporine first revolutionized the 

treatment of psoriasis 20 years ago. Almost all investigative and clinical research subsequently, has concentrated on 

elucidating the specifics of antigen presentation, T cell interaction and the production of specific cytokines. The 

role of the keratinocyte, previously thought to be the primary target cell in psoriasis pathogenesis, has been 

relegated to a secondary role and the mechanism of action of systemic methotrexate in psoriasis has been challenged, 

the primary role of the T lymphocyte is now well known. While psoriasis has traditionally been treated "ab initio" 

with topical medications (corticosteroids, vitamin D(3), and retinoid derivatives), either singly, in combination, or 

with ultraviolet B (UVB) or psoralens and ultraviolet A (PUVA) therapy, the role of systemic medications has assumed 

greater prominence. Thus, three systemic medications currently are approved worldwide for the treatment of moderate to 

severe forms of psoriasis, namely cyclosporine, methotrexate and acitretin. The first two are likely to give 

significant clearing (greater than 75%) in the majority of cases, whereas acitretin is significantly less effective as 

monotherapy, but may approach methotrexate and cyclosporine in efficacy, if combined with PUVA or UVB phototherapy. 

The main limitations of these three drugs remain organ toxicity, especially hepatic toxicity with methotrexate, 

hypertension and nephrotoxicity with cyclosporine, and teratogenicity and mucocutaneous toxicity with acitretin. Thus, 

the need for more specific systemic therapy, targeting the T lymphocyte. This has become the major area of clinical 

research interest over the past 5 years, with the promise of longer-term disease control (improved remissions) and 

less organ toxicities. Currently, there are over 15 of these "biologic" drugs in various stages of development and 

clinical trials, either by the subcutaneous, intramuscular or intravenous route. The three main variables are the 

rapidity of onset, percentages of improvement and remission rates. Without exception, these new systemic agents appear 

to be remarkably free of systemic organ toxicities (liver, renal, bone-marrow, etc.), with adverse effects being 

limited to mild flu-like symptoms with the anticipated increase in infections (e.g., herpes simplex) being either 

equal to placebo or only marginally increased. Not all these agents under evaluation give clinical responses equal to 

methotrexate or cyclosporine (75% or greater clearing in 75% of cases). In addition, response rates may be slower with 

some therapies versus others. However, the need for intermittent administration even by the injectable route, longer 

remissions, lack of systemic organ toxicities and the potential for safer usage in females of child-bearing age, make 

a compelling argument for widespread acceptance by both patients and the dermatological community. Other modalities 

under clinical evaluation include vitamin D and retinoid drugs, topically and systemically, with effects on nuclear 

receptors, as well as more specific wavelengths (308 to 311 nm) of UVB phototherapy with application for more 

localized forms of psoriasis. For the 2 to 3% of the worldwide population of patients with psoriasis the future has 

never looked brighter.

www.kerneluvb.com----The leader manufacturer of UVB Phototherapy.