Safety and Efficacy of the Tumor Necrosis Factor Antagonists
Psoriasis is one of the most common systemic inflammatory diseases and affects the quality of
life of the affected persons profoundly. Further knowledge of the pathogenesis and new
biotechnological techniques have made it possible to develop new targeted therapies, such as
antibodies against tumor necrosis factor (TNF)-alpha. Today, 3 TNF inhibitors, infliximab,
adalimumab, and Etanercept, have been approved for the treatment of psoriasis arthritis,
psoriasis, and other indications like Crohn’s disease, depending on the distinct substance by
the European Medicines Agency. Golimumab was approved in September 2009 for the use in
psoriasis arthritis, respectively. These substances have added new effective treatment options
to the therapeutic armamentarium of psoriasis. To use these new treatments for the best of our
patients, it is important to know the correct application, the advantages, as well as contraindications
or possible adverse effects of the substances. This article provides an update on the
TNF-alpha inhibitors with emphasis on practical daily use. Most data are on the basis of
high-quality studies and official guidelines, but if necessary, data from recent publications or
clinical expertise have been added. In summary, with TNF inhibitors we have gained effective
new treatment options showing a favorable safety profile when paying attention to safety
aspects before and during therapy (screening, monitoring).
Semin Cutan Med Surg 29:35-47 © 2010 Elsevier Inc. All rights reserved.
Anti-p40 Antibodies Ustekinumab and Briakinumab: Blockade of Interleukin-12 and Interleukin-23 in the Treatment of Psoriasis
The choice of therapeutic agents for patients with moderate-to-severe psoriasis has expanded
significantly in the past decade. With new understanding of the immunologic basis
of psoriasis, multiple new potential targets for therapy have been identified. It is likely that
a series of new medications to focus on the newly identified pathways is on the horizon. The
first pathway targeted by new medications focuses on the p40 subunit that is shared by
interleukin (IL)-12 and IL-23. Two human anti-p40 antibodies have been used therapeutically
in psoriasis to date, ustekinumab (CNTO-1275, Stelara, Centocor, Horsham, PA) and
briakinumab (ABT-874, Abbott, Abbott Park, IL). Ustekinumab was recently approved by the
United States Food and Drug Administration, making it the first medication approved in the
United States to work by this pathway while briakinumab is currently in phase III clinical
trials.
Semin Cutan Med Surg 29:48-52 © 2010 Elsevier Inc. All rights reserved.
Psoriasis in Children and Women: Addressing Some Special Needs
This article addresses some of the challenges in two special populations: children and women of childbearing potential.
Alefacept for Psoriasis
Alefacept was the first biological agent approved by the
Food and Drug Administration for the treatment of psoriasis.
Alefacept was initially approved as an intravenous and
intramuscular medication. It is available only as an intramuscular
medication. Alefacept is an immunosuppressive dimeric
fusion protein that consists of the extracellular CD2-binding
portion of the human leukocyte function antigen-3 linked to
the Fc (hinge, CH2, CH3 domains) portion of human immunoglobulin
G.1 Alefacept selectively blocks the leukocyte
function antigen-3:CD2 costimulatory pathway, which is important
in the reactivation of memory effector T cells. Alefacept
also reduces the number of memory effector T cells in
the blood and in the skin.2
Alefacept is indicated for the treatment of adult patients
with moderate-to-severe chronic plaque psoriasis who are
candidates for systemic therapy or phototherapy. The recommended
dose of alefacept is 15 mg given once weekly as an
intramuscular (IM) injection. The approved regimen is a
course of 12 weekly injections. Retreatment with an additional
12-week course may be initiated if CD4 T lymphocyte
counts are within the normal range and a minimum of a
12-week interval has passed since the previous course of
treatment. Alefacept is Pregnancy category B. It should only
be used when clinically indicated in pregnant women and
nursing mothers.
Treatment of Psoriatic Arthritis with Biological Agents
Psoriatic arthritis (PsA) is an inflammatory arthritis that occurs in individuals with psoriasis.
The primary goals in the treatment of PsA are reduction of pain; improvement in the other
signs and symptoms of disease, including skin and nail involvement; optimization of
functional capacity and quality of life; and inhibition of the progression of joint damage.
These goals should be achieved while minimizing potential toxicities from treatment. The
management of PsA should simultaneously target arthritis, skin disease, and other manifestations
of PsA, including involvement of the axial skeleton, dactylitis, enthesitis, and eye
inflammation. In this respect targeted biological agents, primarily tumor necrosis factor
inhibitors, have emerged as generally well tolerated and highly effective alternatives to
traditional disease modifying antirheumatic drugs. Herein we review the evidence regarding
the treatment of PsA arthritis with biological agents.
Semin Cutan Med Surg 29:56-62 Published by Elsevier Inc.