Old and New Biological Therapies for Psoriasis

Abstract

Biological therapy became available for psoriasis with the introduction of alefacept at the beginning of this century. Up to then, systemic treatment options comprised small molecule drugs, targeting the immune system in a non-specific manner. The first biologics targeted T-cell activation and migration and served as an alternative to small molecules. However, significant improvement in outcome was first accomplished with the introduction of tumor necrosis factor-α inhibitors that were already approved for other inflammatory disorders, including rheumatic diseases. Along with the progress in understanding psoriasis pathogenesis, highly targeted and effective therapies have since developed with the perspective not only to improve but to clear psoriasis. These accomplishments enable future achievement of advanced goals to individualize treatment best suited for each patient. Mechanistic studies with patients treated with the new highly targeted biologics may guide us towards these goals. This review offers an overview of biologics developed for psoriasis and illustrate a historical progress in the treatment of this common chronic inflammatory skin condition.

Is the humoral immunity dispensable for the pathogenesis of psoriasis?

“…Consistent with this genetic line of argumentation, microarray data, including ours, as well as big GWAS have mainly found aberrations in T‐cell and not B‐cell‐related pathways . Not least our immunofluorescence stainings revealed that B cells are rarely found in psoriatic skin as compared to the dense infiltrate of T cells providing one reason why B‐cell‐depleting therapies have not proven resounding success for the therapy of psoriasis in contrast to the successful target‐oriented therapies that are focused on T‐cell‐mediated pathways …”

Safety of selective IL‐23p19 inhibitors for the treatment of psoriasis

“…Consequently, the long‐term safety and tolerability of any treatment are critical to effective prescribing. Early biologic agents for the treatment of psoriasis typically induced non‐specific immunosuppression, including agents targeting T‐cell activation and migration (efalizumab and alefacept, both of which have now been withdrawn) and anti‐TNF agents that target a key cytokine involved in most inflammatory and infectious processes in the body . TNF antagonists have been associated with increased risk of serious bacterial, viral and fungal infections in patients with psoriasis, including active tuberculosis and reactivation of latent tuberculosis infection .…”

Patient preference for biologic treatments of psoriasis in Japan

“…Biologics inhibit the action of specific types of immune‐mediated cells, or inhibit the binding of proteins which play a role in the immune system in developing psoriasis, including pathways such as tumor necrosis factor (TNF)‐α, interleukin (IL)‐17A or IL‐23 . Among those targets, IL‐23/IL‐17 was detected as an immune axis and the discovery has brought further understanding of the role of cellular immunology in psoriasis .…”

“…The Psoriasis Area and Severity Index (PASI) is a well‐accepted scoring system used to evaluate the severity of psoriasis. A PASI‐90, interpreted as a 90% or more improvement from baseline PASI score, was adopted as the primary efficacy endpoint in recent clinical trial programs of biologics, and it was achieved in the majority of patients with the new biologics . Some biologics can demonstrate the attainment of even higher efficacy of PASI‐100 (i.e.…”