Biologic therapy, also known as immunotherapy, is a
treatment that aims to restore the ability of the body's immune system to fight
infection and disease. Immunosuppressive drugs are prescribed generally to
reduce the body's immune response for the treatment of certain systemic
The biological compounds, such as
tumor necrosis factor-alpha (TNF-α) inhibitors and ustekinumab, involved in
biologic therapy are composed of antibodies or other peptides that act through
one of the following modes -
• Inhibiting inflammatory cytokine signaling especially Tumor Necrosis
Factor or TNF. This means, anti-TNF monoclonal antibody drugs such as
Infliximab and adalimumab, and etanercept suppress the activity of the
pro-inflammatory cytokine called TNF-alpha responsible for increasing plasma
concentrations in response to inflammation thus causing clinical problems
associated with psoriasis and other inflammatory diseases.
• Inhibiting activation of T-cells, which play a key role in cell
mediated immunity (an immune response that does not involve antibodies).
• Depleting B- cells, which cause certain systemic inflammatory
Although these immune modulating
drugs are generally regarded as safe and efficacious for a number of diseases,
the risk of infection is a major concern with long term immunosuppressive
So, Rachel Gordon and colleagues
from Houston, USA, took up a review study of literature regarding the risk of
infection with tumor necrosis factor-alpha (TNF-α) inhibitors and ustekinumab.
The researchers had come up with
the following findings -
• Of the TNF inhibitors,
infliximab seems to carry the highest risk of infection. In comparison to
infliximab, use of etanercept, abatacept, rituximab, and adalimumab was
associated with lower rates of hospitalized infections.
• There is a significantly higher
risk of Herpes Zoster (shingles) in rheumatoid arthritis patients treated with
etanercept, infliximab, or adalimumab compared with conventional
disease-modifying antirheumatic drugs (DMARDs). This was found to be
conflicting with another study, which associated the treatment with TNF-α
inhibitors with a lower incidence of post-herpetic neuralgia.
• The risk of latent tuberculosis
(TB) reactivation in patients treated with biologics is well established. A
Spanish study of psoriasis patients receiving any anti-TNF therapy found a 29
percent incidence of latent TB infection (LTBI).
Rheumatoid arthritis patients
treated with TNF-α antagonists had an increased rate of Listeria infection in
comparison those treated with conventional therapy. A review, which had identified
92 cases of L. monocytogenes infections related to infliximab treatment found
Meningitis to be the most common type of infection reported.
• As the relative risk of developing L. pneumophila
during treatment with TNF inhibitors is not well established, the authors
suggest that clinicians to consider antibiotic treatment for Legionella in
patients on anti-TNF- α therapy with pulmonary symptoms.
• In 2008, the FDA had alerted
the clinicians of the risk of endemic fungal infections in patients receiving
anti-TNF-α therapy with infliximab, etanercept, or adalimumab.
• The overwhelming majority of
evidence supports the idea that biologics are safe for the treatment of
However, the reviewers find it
difficult to predict the true risk of inflammation in patients because in most
of the studies of the patients were treated for conditions other than psoriasis
and also additional systemic immunosuppressive therapy were utilized.
The authors thus concluded - 'The
benefits of biologics outweigh the risks and that clinical practice measures
such as screening, prevention, and vigilance are effective in limiting the risk
of potential opportunistic infections associated with immunotherapy'.
Source: Gordon R, Mays R, Doan H, Lapolla W, Tyring S.
Biologic therapy and risk of infection. Skin Therapy Lett. 2012 Apr;17(4):1-4.