Exploring Pathogenesis and Treatment Response in Different Disease Phenotypes in Spondyloarthritis

Background: The pathogenesis of spondyloarthritis (SpA) is thought to be driven by enthesitis, yet there remain gaps in the understanding of these diseases. Different SpA phenotypes characterised by inflammatory entheseal/joint pathology may result in structural/functional damage. Despite therapeutic advances, challenges in measuring treatment responses persist. Objectives: To explore the: (i) pathogenesis of severe SpA in different phenotypes; (ii) clinical/ultrasound (US) characteristics of early PsA; (iii) significance of dactylitis and disease severity in early PsA; (iv) mechanisms of measuring treatment response in infliximab (IFX) treated SpA. Methods: (i) Two separate clinical case series evaluations were conducted in patients with severe SpA phenotypes. (ii/iii) A prospective observational clinical/ultrasound (US) study was conducted to examine characteristics of DMARD-naive early PsA, and significance of dactylitis. A prospective clinical evaluation was performed to assess IFX drug trough levels (DLs), anti-drug antibodies (ADAs), and treatment responses (iv). Results: (i) Severe enthesitis was found in a phenotype mimicking appearances of infection. De novo severe SpA and enthesitis manifested following successful vedolizumab (VDZ) treated inflammatory bowel disease (IBD). (ii) Swollen joints were more likely to have US synovitis than tender joints in early PsA. (iii) The presence of dactylitis was found to be significantly associated with greater SJC, CRP, US synovitis and US erosions in early PsA. (iv) Measuring DLs/ADAs in IFX treated SpA enabled rationalisation of treatment responses. Conclusion: Severe enthesitis was identified in extreme SpA phenotypes likely to resemble ReA, and paradoxical reactions to VDZ. Swollen joints were the better proxy for US synovitis than tender joints, and dactylitis represented a marker for a phenotype of greater disease severity in early PsA. Use of DL/ADAs to IFX treated SpA may support rationalisation of treatment responses. These findings add to the knowledge and understanding of disease in SpA, and contribute towards improving the care of patients.