Ultrasound-Detected Enthesitis Response to Advanced Therapies in Psoriatic Arthritis: A Real-World Study Highlighting Greater Improvement with IL-17 Inhibitors

Objectives Enthesitis is a hallmark manifestation of psoriatic arthritis (PsA). The IL-17/IL-23 pathways play pivotal roles in its underlying pathogenesis. However, head-to-head comparative data on enthesitis outcomes across different advanced therapy (AT) mechanisms remain limited. In this study, we compare ultrasound-detected enthesitis responses among patients with PsA initiating various ATs. Methods At the ORCHESTRA (Ottawa Rheumatology CompreHEnSive TReatment and Assessment) Clinic, PsA patients initiating a new AT undergo a protocolized ultrasound (US) examination, at baseline and 3 months post therapy assessing 14 entheses for elementary lesions: hypoechogenicity, thickening, and power Doppler signal (inflammatory features), as well as erosions, calcifications, and enthesophytes (damage features), each graded on a 0–3 scale (none, mild, moderate, severe). These were summed to calculate per-patient inflammation and damage scores. Patients were categorized into 3 groups by treatment mechanism: anti-TNF agents (TNFi), JAK inhibitors (JAKi), and IL-17 inhibitors (IL-17i). Due to sample size limitations, JAKi or TNFi were combined when analyzing bio-naïve and bio-experienced subgroups. Baseline and three-month disease activity indices and US scores were compared. Results Sixty-two patients who had 3 months follow-up were included, 27 of whom (43.5%) were AT-naïve. 20 patients (32.3%) initiated TNFi, 10 patients (16.1%) initiated JAKi, and 32 patients (51.6%) initiated IL-17i. Baseline disease activity and US findings were similar across groups. However, US-entheseal inflammation scores differed at follow-up (p = 0.025), with lower scores in patients receiving IL17i compared with JAKi (2 [0–6.5] vs 6.5 [3.5–12]; p = 0.036) and a trend of higher reductions in patients receiving IL-17i compared with JAKi or TNFi (Table). Among biologic-experienced patients, despite having similar baseline clinical and US scores, follow-up enthesis inflammation scores were lower with IL-17i (1 [0–4] vs 7 [4.5–11.5]; p = 0.001) with higher reduction at 3 months then others (4 [0–8] vs 0 [−4–4]; p = 0.049). More IL-17i recipients demonstrated reduced entheseal Doppler signal (7 [31.8%] vs 0 [0%]; p = 0.031) (Table). Same differences were not seen in bio-naïve patients (data not shown). Conclusion In this real-world cohort of PsA patients initiating AT, IL-17i were associated with greater improvement in US-detected entheseal inflammation compared with JAKi and TNFi, particularly among biologic-experienced patients. These findings support a potential preferential effect of IL-17 blockade on entheseal inflammation, consistent with its pathogenic role. US proved a sensitive tool for detecting early treatment-related changes, highlighting its value in evaluating therapeutic response in PsA.