Evaluating ultrasound confirmed enthesitis as a predictive marker for response to biologic therapy in psoriatic arthritis

Abstract

Psoriatic Arthritis is a chronic inflammatory arthritis that occurs in up to a third of patients with psoriasis. It is a heterogeneous condition that can cause long lasting joint damage and morbidity. It now has a range of effective treatments, in particular the biologic agents for moderate to severe disease. There is however no effective biomarkers that can predict response or allow us to decide between biologic treatments based on the musculoskeletal manifestations of psoriatic disease.

An enthesis is the site where the tendon, ligament or joint capsule inserts into the bone to facilitate joint motion. Enthesitis is inflammation at these sites, causing pain and is a hallmark of psoriatic arthritis. It appears to be an aspect of the disease that is implicated in the pathogenesis, diagnosis and prognosis of Psoriatic Arthritis but is understudied.

This thesis aimed to better understand psoriatic arthritis and its response to treatment with the linking of clinical assessment, imaging and proteomic analysis.

To achieve these aims a clinical study was carried out (Psoriatic Arthritis UltraSound of enthesitis study - PsAUSe) in which patients were assessed with psoriatic arthritis before starting their first biologic therapy and then at 16 weeks of biologic treatment. Clinical assessment, bedside ultrasound imaging and blood sampling was taken at both time points. This thesis has for the first time compared the effect on ultrasound confirmed enthesitis between different forms of biologic therapy for PsA and demonstrated an overall reduction in enthesitis scoring with biologic treatment. There was a larger reduction in active entheseal disease for TNFi versus secukinumab that merits further exploration. An exploratory sub study has been able to additionally assess the relationship with ultrasound between the nail bed and peripheral entheseal disease in psoriatic arthritis.

Further proteomic work identified a panel of candidate biomarkers that are related to enthesitis on imaging and response to treatment. This is the first study to examine the proteome to assess its relationship with objective enthesitis. The thesis identified a set of proteins that are associated with both overall treatment response and then by class of biologic agent administered.

Date of Award	Jul 2024
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	GRAPPA, Irish Society for Rheumatology, BMA Doris Hillier Foundation & Psoriasis and Psoriatic Arthritis Alliance
Supervisor	Gary Wright (Supervisor) & Madeleine Rooney (Supervisor)