# Increased synovial and entheseal fibroblast activation detected by 68Ga-FAPI-PET/CT is associated with the development of psoriatic arthritis in psoriasis patients with arthralgia

## TL;DR

This study shows that increased fibroblast activity in psoriasis patients with joint pain, detected using a special imaging technique, is linked to a higher risk of developing psoriatic arthritis.

## Contribution

The study introduces 68Ga-FAPI-PET/CT as a novel imaging tool to detect fibroblast activation and predict psoriatic arthritis progression in psoriasis patients.

## Key findings

- 68Ga-FAPI uptake was observed in 82% of psoriasis patients with arthralgia.
- FAPI-positive patients had higher BMI and disease activity scores.
- FAPI-positive patients had a significantly higher risk of progressing to psoriatic arthritis.

## Abstract

To assess the clinical and imaging characteristics associated with fibroblast activation detected by 68Gallium-labelled fibroblast activation protein inhibitor positron emission tomography/CT (68Ga-FAPI-PET/CT) in patients with psoriasis and whether 68Ga-FAPI uptake correlates with the risk of progression to psoriatic arthritis (PsA).

Psoriasis patients with arthralgia underwent 68Ga-FAPI-PET/CT and were followed up prospectively. 68Ga-FAPI uptake was assessed at 71 articular sites and patients with ≥1 joint with 68Ga-FAPI uptake and PET/CT Joint Index≥2 were considered FAPI positive. The associations between FAPI uptake and clinical and ultrasound (US) findings were investigated. Survival analyses were conducted to assess the association between 68Ga-FAPI uptake and progression to PsA.

45 patients with psoriasis were enrolled, 37 of whom (82%) were FAPI positive. FAPI-positive psoriasis patients had significantly higher body mass index (BMI) (p=0.036) and Disease Activity Score 28-C reactive protein (p=0.033) compared with FAPI-negative patients. 68Ga-FAPI uptake was most frequent in large joints and mechanically stressed sites and was more likely in the presence of low-grade synovial hyperplasia (OR: 1.77, 95% CI 1.08 to 2.89), entheseal Power Doppler (OR: 3.80, 95% CI 1.66 to 8.72) and concomitant osteoarthritis (OA). FAPI-positive patients showed a higher risk of progression to PsA compared with FAPI-negative patients (HR 7.1, 95% CI 0.9 to 53.6) (log-rank p=0.028). Only 1/8 patients with psoriasis (12.5%) without 68Ga-FAPI uptake developed PsA, as opposed to 18/37 (49%) of FAPI-positive patients.

In psoriasis patients with arthralgia, 68Ga-FAPI uptake, indicating fibroblast activation, is associated with higher BMI, more pain, subclinical US changes and concomitant OA. Pathological 68Ga-FAPI uptake at articular sites was indicative of higher risk of progression to PsA in our cohort, suggesting fibroblast activation as a crucial step to develop PsA.