Infections Associated With the Use of Tumor Necrosis Factor-α Inhibitors in Psoriasis
March 2013 | Volume 12 | Issue 3 | Original Article | 41 | Copyright © March 2013
Xi Tan PharmD,a Steven R. Feldman MD PhD,b and Rajesh Balkrishnan PhDa
aDepartment of Clinical, Social and Administrative Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI bDepartment of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC
Tumor necrosis factor (TNF)-α inhibitors have been shown to increase the risks of overall infection and serious infection in rheumatoid arthritis. However, it is uncertain whether we can draw the same conclusion in the psoriatic population. This article focuses on the 3 most commonly used TNF-α inhibitors in psoriasis: adalimumab, etanercept, and infliximab. In order to assess the risks of overall infection and serious infection in patients with psoriasis, we reviewed the underlying mechanism of the potential infection risk, different types of serious infection associated with TNF-α inhibitors, and current evidence in the psoriatic population. Results from 11 randomized controlled trials and open-label extension studies showed that there was no apparent significant association between the use of TNF-α inhibitors and increasing risks of overall infection and serious infection. Becasue of the limitations of current evidence, large, long-term follow-up studies with appropriate control groups using real-life data, such as postmarket surveillance, are warranted. J Drugs Dermatol.
Psoriasis is a chronic immune-mediated disease characterized
by red papules and plaques with a silver scale, and it affects 0.6% to 4.8% of the world population and approximately
2.2% of the US population.1-3 Psoriasis has a significant impact on patients’ quality of life and is associated with an increased
risk of cardiovascular disease, metabolic syndrome, and cancer.1 Moderate to severe psoriatic disease usually requires phototherapy or systemic therapy, including biologic agents such as tumor necrosis factor (TNF)-α inhibitors.
Although TNF-α inhibitors are effective and commonly used in treating psoriasis, drug safety is a consistent, long-term concern for physicians prescribing these drugs.4 One of the key safety concerns about TNF-α inhibitors is the risk of overall
infection or serious infection, especially tuberculosis (TB). The majority of available information regarding this safety concern is from the patients with rheumatoid arthritis (RA) and Crohn’s disease. Evidence from observational studies, surveillance reports, and systemic reviews and meta-analyses
of randomized controlled trials suggests increased risks of infection and serious infection in patients with RA.5-10 Whether we can draw the same conclusion in the psoriatic population is uncertain. Patients with psoriasis are usually treated with monotherapy rather than concomitant immunosuppressive
agents, such as methotrexate and prednisone. Patients with psoriasis also have different comorbidities and may be a generally healthier patient population than the RA population. RA itself is a risk factor for infectious diseases, whereas this is not thought to be the case for psoriasis. Therefore, infection rates in RA cannot be generalized to the psoriatic population without further investigation.
Because of the limited evidence in patients with psoriasis, it is still controversial as to whether or not TNF-α inhibitors increase
the risk of infection or serious infection in treating psoriasis. This systemic review discusses the mechanism of TNF-α inhibitors and different types of serious infection associated
with them,11-27 current evidence in the psoriatic population,28-38 and implications for future research.
TNF-α and TNF-α Inhibitors
TNF-α is a proinflammatory cytokine that mediates inflammation
and immune functions.11 TNF-α is involved in a variety of immunological and physiologic processes, such as the recruitment
of inflammatory cells to the sites of infection, cell activation, maintenance and formation of granulomas, and the induction of cytokines and adhesion molecules.11,12 TNF-α inhibitors block these processes, which results in reducing the expression of pattern-recognition receptors, decreasing the production of interferon α, increasing monocyte apoptosis, and the deterioration of granulomas.11 Overall, TNF-α inhibitors
intervene in the host’s immune resistance against several infectious microorganisms such as Mycobacterium tuberculosis,
Listeria monocytogenes, and Pneumocystis jiroveci. This is why there is particular concern about the increasing risk of infection—especially TB—associated with the use of TNF-α inhibitors. This article focuses on the 3 most commonly used TNF-α inhibitors for treating moderate to severe psoriasis: adalimumab, etanercept, and infliximab. These 3 drugs have been approved to treat psoriasis in the United States, the European
Union, and other regions.13