Abstract
Psoriasis and psoriatic arthritis, together known as psoriatic disease, is highly prevalent chronic relapsing inflammatory disease affecting skin, joints or both and is associated with several comorbidities such as cardiovascular, metabolic, psychiatric, renal disease etc. The etiopathogenesis of psoriasis is complex and mainly driven by aberrant immune response owing to the genetic susceptibility and various environmental factors such as trauma, infections and drugs. Recent advances in understanding molecular and cellular pathways have identified tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-23, IL-22 as major contributors in psoriasis pathogenesis. Advances in the knowledge of pathophysiology, the interaction of autoinflammation and clinical phenotypes have led to the development of highly effective targeted therapeutic agents which include TNF-α, IL-17, IL-23, IL-1 α/β or IL-36 inhibitors or receptor blockers, small molecule drugs like phosphodiesterase-4 inhibitors (apremilast), Janus kinase (JAK) inhibitors, retinoic acid receptor-related orphan receptor γt (RORγt) inhibitors. These novel drugs have promised the potential of improved disease control. In recent years, the transition from biologics to biosimilars especially with TNF-α inhibitors had significant impact on decreasing health care cost and increasing therapeutic options to the patients. However, selection of right treatment for an individual patient still remains challenging. Moreover, interplay between different epigenetic mechanisms such as the DNA methylation, chromatin modifications and noncoding RNA regulation has recently been started to be deciphered. Enzymes inhibitors involved in epigenetic pathways such as DNA methyltransferases and histone deacetylases demonstrated to restore normal epigenetic patterns in clinical settings and have provided the potential as novel therapeutic targets for psoriasis. In this review, we will discuss novel biologic agents and newer therapeutic approaches in treatment of psoriatic disease.
Highlights
Psoriatic disease is a chronic relapsing inflammatory condition affecting ∼2–3% of population [1, 2]
Psoriatic disease consists of psoriasis vulgaris affecting skin and psoriatic arthritis affecting joints
The immunopathogenesis of psoriasis is complex primarily driven by an aberrant immune response further modified by an interplay between genetic susceptibility
Summary
Psoriatic disease is a chronic relapsing inflammatory condition affecting ∼2–3% of population [1, 2]. Baricitinib, an oral highly selective JAK1 and JAK2 inhibitor has been studied in patients with moderate-to-severe psoriasis in Phase II trials and has shown better efficacy as compared to placebo at doses 8 mg and 10 mg [19]. IL-23 leads to the production of cytokines from Th-17 cells i.e., IL-17, a major cytokine implicated in the pathogenesis of psoriasis [28] This led to development of anti-IL23 biologics in the therapeutics of psoriatic disease. Studies in mouse model have observed psoriasis like epidermal changes, inflammatory cell infiltrate and gene dysregulation after IL-36 administration which was not seen when Pre-treatment with an IL-36 antagonist was administered [42] This supports a direct role of IL-36 in psoriasis pathogenesis and attenuating this signaling pathway may be an effective alternative approach to the already approved small molecules such as apremilast or other biologics. Tofacitinib 5 mg−107; 10 mg−104; adalimumab- 106; placebo- (5 mg switch), (10 mg switch)
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