Anti-TNF agents for the treatment of psoriasis.
BACKGROUND
Psoriasis is one of several systemic diseases that presents chiefly with cutaneous symptoms and has the potential to negatively impact patients' overall health and quality of life. Physicians who treat patients with psoriasis must be cognizant of the chronic, lifelong character of the disease and of the potential for multisystem pathology. According to the National Institutes of Health (NIH), between 5.8 and 7.5 million persons in the U.S.--approximately 2.2% of the population--have psoriasis; worldwide, it affects an estimated 125 million people. The annual cost of treating psoriasis may exceed $3 billion annually. Immunologic mechanisms are now accepted as the pathophysiologic basis for the development of psoriatic disease. Treatment strategies--which include topical treatment, phototherapy, methtrexate, cyclosporine and acitretin--also encompass several biologic agents that target immune mediators associated with the condition.


CONCLUSIONS
Patients with mild disease may obtain symptomatic relief with topical agents and targeted phototherapy. Patients with moderate-to-severe disease are likely to benefit from systemic therapy. Shortcomings of the traditional agents, particularly their adverse event profiles, have motivated research and development of biologic agents. Currently three anti-TNF agents--etanercept, infliximab and adalimumab--are FDA-approved for treatment of psoriasis. Differences exist among study designs and, therefore, in interpretation of data; however, the improvements observed in the psoriasis study populations participating in clinical trials are dramatic. Long-term clinical data continue to accumulate and demonstrate sustained benefits with anti-TNF agents. Safety data also continue to be collected over the long-term; key safety considerations are infection, cytopenia, demyelinating disease, lupus-like syndromes, congestive heart failure and malignancies. Combination therapy should also be considered when managing psoriasis for such reasons as augmenting an inadequate response to monotherapy or improving tolerability. Combination therapy with an anti-TNF agent and phototherapy has shown considerably higher rates of response compared with either intervention alone.


OBJECTIVE
The objective of this paper is to critically examine the anti-TNF studies to assess the efficacy and safety of the agents in patients with psoriasis and determine applicability of the data in clinical practice. In light of the chronic nature of this disease, the emphasis will be on the longest-term data available.


CONCLUSIONS
The treatment of plaque psoriasis with TNF-alpha antagonists is still a relatively recent addition to the pharmacologic armamentarium available to clinicians. The collection of long-term data is, therefore, small but growing as results from newer studies emerge. From the data reviewed here, the clinician can attempt to arrive at a satisfactory assessment of the benefits and risks of treatment with these agents.
Kircik
Leon H
LH
Indiana University Medical Center, Indianapolis, Indiana, USA. wedoderma@bellsouth.net
Del Rosso
James Q
JQ
D000068879:Adalimumab; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D000069285:Infliximab; D011565:Psoriasis / Q000188:drug therapy*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept