Targeted therapy seems untargeted: TNF-α antagonists in psoriasis as an example

Area of Science:

• Immunology
• Dermatology
• Pharmacology

Background:

• Psoriasis treatment increasingly utilizes biologic therapies.
• Biologics are often considered targeted treatments based on their specific molecular targets.
• The complexity of the cytokine network in psoriasis questions the narrow definition of targeted therapy.

Purpose of the Study:

• To review the literature on the impact of tumor necrosis factor-alpha (TNF-α) antagonists on the cytokine profile and immunocytes in psoriasis.
• To evaluate whether TNF-α antagonists should be broadly classified as targeted therapies.
• To discuss the clinical implications of the pleiotropic effects of TNF-α antagonists.

Main Methods:

• Literature review focusing on studies examining TNF-α antagonists in psoriasis.
• Analysis of the effects of TNF-α antagonists on cytokine profiles (e.g., IL-1, IL-6, IL-17, IL-23).
• Assessment of the impact on immunocyte populations (e.g., neutrophils).

Main Results:

• TNF-α antagonists significantly influence a wide range of cytokines in both blood and skin.
• These biologics affect various cytokines of the innate and adaptive immune system, including interferon-gamma and multiple interleukins (IL-1, IL-4, IL-6, IL-8, IL-12, IL-17, IL-22, IL-23, IL-24).
• TNF-α antagonists also alter immunocyte counts, such as neutrophil elastase-positive cells.

Conclusions:

• The functional impact of TNF-α antagonists extends beyond their specific molecular target.
• Biologic treatments, while structurally designed for specific targets, exhibit broader immunomodulatory effects.
• Understanding these widespread effects is crucial for predicting and managing potential side effects like colitis, inflammatory bowel disease, myocarditis, and infections.