PSORIASIS AND BIOLOGICS
New Insights in the Immunologic Basis of Psoriasis
Psoriasis vulgaris is a multifactorial heritable disease characterized by severe inflammation
resulting in poorly differentiated, hyperproliferative keratinocytes. Recent advances in
genetic analyses have implicated components regulating the interleukin (IL)-23 and nuclear
factor-B pathways as risk factors for psoriasis. These inflammatory pathways exhibit
increased activity in skin lesions, and promote secretion of various cytokines, such as IL-17
and IL-22. Unrestrained, the activated inflammatory cytokine network in psoriasis may
trigger a vicious cycle of inflammation and cellular proliferation that ultimately results in
lesion formation. These advances in genetic analyses, together with the progress made in
targeted biological therapy, pave the path to tailor treatment on the basis of an individual’s
genetic and immunologic profile.
Semin Cutan Med Surg 29:3-9 © 2010 Elsevier Inc. All rights reserved.
Comorbidities in Psoriasis Patients
Psoriasis is a chronic inflammatory disorder that affects approximately 2% of the general
population. Numerous studies have evaluated the increased prevalence of comorbid diseases
and risk factors in psoriatic patients, including obesity, metabolic syndrome, cardiovascular
disease, psoriatic arthritis, autoimmune disease, psychiatric illness, liver disease,
smoking, malignancy, chronic obstructive pulmonary disease, sleep apnea, and alcohol
abuse. Insight into the overlapping pathogenesis of these comorbidities of psoriasis
highlights the importance of immune-mediated mechanisms in these disease states. Psoriasis,
with its comorbidities, must be approached in a multidisciplinary manner to effectively
and comprehensively understand, manage, and treat those with this complex
Semin Cutan Med Surg 29:10-15 © 2010 Elsevier Inc. All rights reserved.
Assessing Long-Term Drug Safety: Lessons (Re) Learned from Raptiva
Efalizumab was approved for moderate to severe psoriasis in 2003 based on studies in
approximately 2700 patients, of whom only 218 were exposed to the drug for more than 1
year. In 2009, after more than 46,000 patients were exposed to efalizumab, the drug was
withdrawn from the market after 3 confirmed and 1 suspected case of progressive multifocal
leukoencephalopathy (PML) were spontaneously reported. As PML is very rare, it is
extremely unlikely that the 4 reported cases were due to chance and given that PML occurs
primarily in patients who are immunosuppressed, the association is likely causal. The
identification of PML as a serious, but statistically rare risk of efalizumab demonstrates the
strengths and weaknesses of the current drug approval and pharmacovigilance processes
for fully measuring the safety of a drug. Patients and clinicians need to be aware of the
relative completeness and limitations of existing safety data of a drug when selecting a
Semin Cutan Med Surg 29:16-19 © 2010 Elsevier Inc. All rights reserved.
The Role of Biologics and Other Systemic Agents in the Treatment of Pediatric Psoriasis
Psoriasis is a chronic inflammatory disease that is not uncommon
in children and adolescents. While exact prevalence
rates of pediatric psoriasis have not been determined,
30% to 40% of adults with psoriasis report onset of their
signs and symptoms before age 16.1-4 Although the diagnosis
of pediatric psoriasis remains predominantly clinical, its presentation
varies in clinical course, distribution, and morphology.
The management of psoriasis in children ranges from
topical medications for mild and moderate disease to the use
of systemic immunomodulatory agents for more severe disease.
None of the systemic medications, including methotrexate,
cyclosporine, and biological agents, such as etanercept,
infliximab, adalimumab, and ustekinumab have
specific indication by the United States Food and Drug Administration
(FDA) for pediatric psoriasis. The pediatric dermatologic
literature has limited studies in which investigators
examine the use of these therapies, unlike the corresponding
adult literature. Subsequently, experts rely on unpublished clinical
experience and studies of these systemic medications for
other pediatric conditions, such as those published in the rheumatologic,
transplant, oncological, and gastroenterologic
literature. In this article, we discuss the systemic treatment
options for pediatric psoriasis, including drug mechanism of
action and associated risks and benefits of treatment, to aid
dermatologists in treating psoriasis in this special population.
The Treatment of Moderate-to-Severe Psoriasis: Prescreening and Monitoring Psoriatic Patients on Biologics
The development of biologics has dramatically altered the treatment of moderate-to-severe
psoriasis while also introducing new standards of care for therapeutic monitoring. Currently,
the biologics approved by the US Food and Drug Administration are divided into 3
classes: T-cell modulators, tumor necrosis factor- inhibitors, and interleukin-12/23 inhibitors.
Although the US Food and Drug Administration has established recommendations for
pre- and peri-treatment screening evaluations, much of the evidence comes from clinical
trials evaluating the short-term safety and efficacy of each medication, rather than longterm
data, or studies that summarize either the appropriateness or feasibility of screening.
Instead of following a blanket algorithm, providers must understand the evidence as it
relates to each medication to determine which tests are appropriate for any specific patient.
This chapter summarizes the current body of evidence and recommends a practical
approach for monitoring psoriasis patients who are receiving biologic therapies.
Semin Cutan Med Surg 29:28-34 © 2010 Elsevier Inc. All rights reserved.