Psoriatic disease (PsD) encompasses a spectrum of chronic inflammatory disorders characterized primarily by psoriasis and psoriatic arthritis (PsA), with heterogenous manifestations across musculoskeletal, dermatologic, and systemic domains [1]. Psoriasis is a chronic inflammatory skin condition that often precedes the onset of PsA, which further complicates disease management by affecting peripheral and axial joints and entheses, in addition to frequently affecting extra-musculoskeletal domains and having a high prevalence of comorbidities [2].

Currently approved therapies for psoriasis primarily target TNF, IL-17, IL-23, and PDE4 pathways, alongside conventional systemic treatments such as methotrexate and cyclosporine [3]. For PsA, therapeutic options similarly include conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) – particularly methotrexate, leflunomide, and sulfasalazine – as well as biologics and small molecules targeting TNF, IL-17, IL-23, PDE4, and JAK signaling pathways [4]. While significant overlaps exist between approved treatments for psoriasis and PsA, certain therapies possess distinct indications; topical therapies and phototherapy are indicated exclusively for psoriasis, whereas select agents, such as leflunomide, sulfasalazine, and abatacept, are solely approved for PsA, highlighting the therapeutic complexity of PsD(4).

Despite this therapeutic arsenal and recent significant advances in treatment options [5], sustained remission remains challenging, with minimal disease activity (MDA) attained in only a minority of patients [6]. This limited success is attributed to multiple factors, including diagnostic delays, limited access to therapy, and suboptimal treatment responses, all of which contribute to increased functional impairment and disease burden [[7], [8], [9]].

In particular, suboptimal responses to therapy have led to the recognition of difficult-to-treat PsA (D2T-PsA), a subset of patients who fail multiple therapies and have evidence of persistent disease activity, for example, via imaging or acute phase reactants, despite available treatment options [[10], [11], [12]]. Given these unmet needs, exploring novel therapeutic strategies targeting diverse pathogenic mechanisms is essential to improve long-term patient outcomes. This review discusses emerging pipeline therapies and innovative treatment strategies aimed at refining personalized management across the entire spectrum of psoriatic disease (Table 1).