Blockade of Interleukin-17 Leads to Shifts From Stage-based Towards Response-based Disease Clusters- Comparative Data From Very Early and Established Psoriatic Arthritis

Background. Limited information exists about the very early forms of psoriatic arthritis. In particular, differences and responsiveness of patient-reportedoutcomes (PROs) in very early as compared to established PsA have not been investigated to date.Methods. Cross-sectional and prospective longitudinal evaluation of PROs related to pain (VAS), physical function (HAQ-DI, SF-36 physical), mental function (SF-36 mental), impact of psoriatic skin (DLQI), joint (PsAID) and global disease (VAS) in two small prospective observational studies on secukinumab 300mg over 6 months in very early disease patients (IVEPSA study; N=20) and established PsA (PSARTROS study; N=20). Cluster analysis was performed at baseline and 24-weeks follow-up.Results. While responses in pain and physical activity-related PROs to secukinumab were more pronounced in established PsA than very early disease, effects on PROs related to general health perception, as well as those related to emotional and mental well-being, were modified in a similar way in very early disease and established PsA. Cluster analysis based on global disease activity and PROs showed that baseline clusters reflected very early disease and established PsA, while during interleukin-17 inhibition these clusters were abolished and new clusters based on differential responses to physically and mentally-oriented PROs formed.Conclusions. Inhibition of IL-17A leads to comprehensive improvement of PROs in patients with very early musculoskeletal involvement in PsA. Most importantly, treatment restructures original patients clusters based on the stage of psoriatic disease and leads to the formation of new clusters that reflect their post-treatment state with respect tophysical and mental-orientated PROs.Trial Registration: NCT02483234