Extracorporeal photochemotherapy in secondary clinical nonresponse to netakimab in patients with psoriasis: case reports

Psoriasis is one of the most prevalent and socially important skin diseases. For a long time, the main treatment approaches included a combination of topical therapies, physiotherapeutic methods, and systemic agents targeting keratinocyte proliferation. Currently, advances in understanding the immunopathogenesis of psoriasis have made the use of genetically engineered therapy the most justified approach. The introduction of this new class of drugs has substantially improved the efficacy and safety of treatment in patients with moderate-to-severe psoriasis. However, a major limitation of genetically engineered therapy is the predictable development of secondary clinical nonresponse during long-term therapy. Traditionally, this phenomenon has been attributed to the formation of anti-drug antibodies against targeted agents; nevertheless, accumulated clinical evidence indicates that loss of clinical response may also occur in the absence of detectable anti-drug antibodies. Current research into the mechanisms underlying secondary clinical nonresponse to genetically engineered therapy has led to the development of new therapeutic approaches for psoriasis treatment aimed at activating alternative immunopathological pathways, including the addition of adjuvant therapy (most commonly methotrexate), switching to another targeted agent, or reinitiation of treatment with the same biologic drug. The article discusses the possibility of using extracorporeal photochemotherapy in the syndrome of secondary clinical ineffectiveness of gene-engineered biological therapy with netakimab in the absence of anti-drug antibodies. Favorable clinical outcomes of the proposed approach are demonstrated in two patients. We discussed possible mechanisms underlying secondary clinical nonresponse, and provided a pathogenetic rationale for the use of extracorporeal photochemotherapy. This method exerts a comprehensive immunomodulatory effect, including induction of lymphocyte apoptosis, modulation of antigen-presenting cell function, induction of regulatory T cells, and alteration of the cytokine profile. Overall, extracorporeal photochemotherapy contributes to the restoration of immune homeostasis, which may lead to the reversal of pathologic immune processes altered by genetically engineered therapy and characteristic of psoriasis, returning them toward the original inflammatory mechanisms.