Benefits of Biologic Therapy Outweigh the Risk of Infection in Treatment of Inflammatory Diseases: A Review Study
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 diseases.
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 treatment.
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 psoriasis.
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'.