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.