Psoriatic arthritis - expanding options, exciting times? (2016)

tinue treatment over 5 years. As such we are faced with a life-long disease in which exis ting guidelines, e.g. those provided by European League Against Rheumatism (EULAR), suggest that the next step upon TNFi failu re remains re-cycling of agents of the same gene ral mode of action. Clinical heterogeneity thus poses two rather fundamental challenges to the clinician. First, is the pathogenesis of each tissue lesion and location mediated via common or disparate pathways? Second, and predicated upon this notion, should we have similar expecta tions of a given intervention in each tissue com partmen t? There is now abundant evidence implicating Interleukin-17 (IL-17) dependent immune pathways in the pathogenesis of cutaneous psoriasis lesions. The presen ce in lesions of several members of the IL-17 superfamily is established and the effector functions mediated via the IL-17 receptor family are consistent with the pathologic changes observed in tissues. The critical hierarchical position of the pathway is strongly sugges ted by the remarkable magnitude and frequency of res ponses seen upon IL-12/23(p40), IL-17A, or IL-17RA blockade in patients with psoriasis. Mode-of-action studies similarly suggest that the IL-17 pathway occupies a pivotal functional position in the hierarchy of the pathologic lesion. There is also evidence of IL-17 pathway expression in PsA – with circulating and tissue Th17 (CD4 and CD8) cell subsets clearly identified with higher frequency and evi dence that IL-17 can mediate activation of rele vant tissue cells including syno vial fibroblasts, osteoclasts, neutrophils and the like. Clinical targeting of IL-12/23(p40), and more recently of IL-17A is also consistent with a functional role for such pathways in manifestations of disease. Ustekinu mab is now appro ved for use in PsA and phase III trial s are ongoing based on encouraging phase II datasets for agents targeting the IL-17 pathway, such as secuki numab and brodalumab. This development is very exciting and offers real hope of therapeutic expansion in terms of available modes of action. However an objective appraisal of the In the last decade, the advent of novel medicines and the implementation of disease activity targeted strategies in the treatment of rheumatoid arthritis (RA) have transformed expectations amongst health care professionals and patients alike. Outcomes are improved, function is often maintained, remission is achieved in a proportion of patients and co-morbidities are reduced. Can the same be said for psoriatic arthritis (PsA) over this time period? Recalling the old school master’s report card – “could do better” might be a not unreasonable response. PsA comprises a heterogeneous clinical presentation that sets out a number of challenges in terms of pathogenetic explanation and therapeutic management. Patients will variously exhibit synovitis, enthesitis and osteitis and will usually also have skin disease across the range of cutaneous and nail manifestations of psoriasis. The radiographic appearances are of complex bone remodeling with evidence of bone loss, new bone formation and entheseal reactions, often co-existing in a given patient or joint. Sophisticated imaging, particularly Magnetic Resonance Imaging (MRI) and ultrasound, imaginatively applied has refined considerably out understanding of the clinical phenotype of disease and increasingly we now recognize that musculoskeletal involvement across the psoriasis spectrum is broader than previously considered and that such recognition may carry prognostic signifi cance. Thus aggressive pro-active interventions with an emphasis on early recognition, detection and treatment of PsA likely re presents an attractive ‘next step forward’. That Tumor Necrosis Factor (TNF) inhi bition has delivered signifi cant progress is not in dispute – indeed it should be celebrated in PsA just as it has been in RA. TNF inhibition delivers robust responses in many PsA patients and clearly reduces radiographic progression and functional decay. Howe ver around half of Tumor Necrosis Factor inhibitors (TNFi) treated patients will discon-