The many faces of psoriatic arthritis – a challenge to treatment to target?

Psoriatic arthritis (PsA) is a multi-faceted disease. It may involve not only the joints in the sense of arthritis , but also the tendons surrounding the joints, leading to swelling of whole digits (dactylitis), or it may lead to inflammation of the entheses (enthesitis). PsA is considered one of the seronegative spondyloarthropathies, because it may also affect the axial system (spondylar-thritis), and it is obviously characterised by the co-presence of psoriatic skin lesions [1]. In addition, PsA is accompanied by a systemic inflammatory reaction, which can be assessed by acute phase measures (e.g., C-reac-tive protein – CRP) or the sedimentation rate. This in-flammatory activity may stem from involvement of any of the organs mentioned above, and may be considered a summation of all systemic inflammatory events of PsA. Finally, and very importantly, patients with PsA suffer from considerable functional loss and impairment of quality of life [2]. Many treatments are now available for management of PsA, including methotrexate (MTX) and other conventional disease-modifying antirheumatic drugs (DMARDs), as well as numerous biological compounds [3]. Interestingly , the response to these compounds differs across the different manifestations of PsA: while MTX is effective for peripheral joint and skin disease, it is not, or at least much less, helpful for axial disease, enthesitis, or dactylitis; while TNF inhibitors appear to act on all manifestations of PsA in a substantial and quite comparable way, other treatment modalities, such as IL-12/IL-23 or apremilast, appear to work more on the skin and less on the joints. All these specifics of PsA are recognised in national and international management recommendations for this disease , such as those provided and updated by the Europe-an League Against Rheumatism (EULAR) [4]. All these differences have led to the belief that PsA is not a homogeneous disease, neither clinically, nor in its therapeutic amenability. While this heterogeneity of PsA is widely appreciated, at the same time it is often – and quite in good faith – ignored when it comes to disease activity assessment: claims to combine assessment of all domains into single scores may – although seemingly practical at first sight – be counterproductive for several reasons. One reason is the ambiguity of the outcome measure that include domains with differential responsiveness to different treatments, as it will be, for example, difficult to discern whether a patient did not respond to treatment, or simply did not respond in all domains …