Despite the substantial benefit of TNFi therapy for psoriatic arthritis, as demonstrated in clinical trials and in over a decade of clinical use globally, there remains an unmet medical need for effective therapies for patients who do not benefit from TNFi initially, lose response over time, or have adverse effects, even with trials of multiple TNFi agents and traditional oral DMARDs. The definition of adequate response (low disease activity or remission) for PsA is evolving, as is the concept of treatment to target. The target of response in PsA is constituted by several clinical domains: arthritis, enthesitis, dactylitis, spondylitis, and dermatitis, all of which effect function and quality of life, and should be considered when determining a comprehensive treatment response.
An understanding of the pathophysiology of the clinical domains of PsA provides a basis for selecting targets of therapy. Many of the pathophysiologic features of PsA overlap with those of rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriasis, and so it is natural to consider effective treatments for these conditions for the treatment of PsA. Preliminary evidence of the effectiveness of drugs with varying mechanism of action, shown to be effective in RA and/or psoriasis, exists or is being developed in PsA and will be reviewed. These include cellular modulators: co-stimulatory blockade agents which modulate T cell activity (abatacept and alefacept) and an agent which ablates B cells (rituximab). Several key pro-inflammatory cytokines other than TNF are being targeted, such as IL-12/23, IL-17, IL-6, and the multiple cytokines inhibited by the JAK inhibitors or the phosphodiesterase 4 (PDE4) inhibitor, apremilast, supported by data in RA, AS, and/or psoriasis.
Disclosure of Interest None Declared