Secondary failure of TNF‐α inhibitors in clinical practice

Tumor necrosis factor alpha (TNF‐α) is a leading inflammatory cytokine that plays a pivotal role in the pathogenesis of psoriasis. In case of a severe course of psoriasis and moderate‐to‐severe disease in which traditional systemic treatments are ineffective or contraindicated, TNF‐α inhibitors (iTNF‐α) are used. This class of drugs includes monoclonal antibodies and a fusion protein (etanercept) and can induce a humoral or cell‐mediated immune response, leading to formation of anti‐drug antibodies (ADAs). The immunogenicity may affect iTNF‐α drug pharmacokinetics, which would lead to hampering the clinical response (secondary drug failure), so a need to increase the drug dose arises. Antibodies against monoclonal antibodies (adalimumab, infliximab) have been associated with diminished clinical response, while against etanercept are non‐neutralizing and appear to have no significant effect on clinical response and treatment safety. Switching of biologic agents may be one strategy in ADA‐associated secondary failure of iTNF‐α. However researches are needed to identify risk factors for ADA development and investigate management strategies for optimized treatment response. The authors reviewed the literature on the effectiveness of iTNF‐α and pointed out the prevention of secondary failure in clinical practice.