Simon Michael Petzinna

Objective: To comparatively evaluate recent adult-onset Still’s disease (AOSD) activity measures—Development and Validation of Disease Activity in AOSD (DAVID), Still’s Disease Activity Score (SDAS), Still Activity Score (SAS) with Pouchot’s Systemic Score (PSS) in an independent multicentre cohort. Methods: DAVID and SDAS were modified (m) by omitting global assessments due to availability and to circumvent incorporation bias. Criterion validity was assessed by receiver operating characteristic (ROC) analysis against the treating physician’s determination of disease activity (active vs inactive). Responsiveness was evaluated by comparing mean change in scores between remission and active disease, and Cohen’s d. Longitudinal sensitivity to change was assessed using linear mixed-effects models with z-standardised scores and marginal R². Primary analysis uses imputed data, with complete-case sensitivity analysis. Results: The cohort comprised 86 patients with initially active AOSD (64% female; mean age 39.4±15.0 years). In ROC analyses, mSDAS, mDAVID and SAS showed comparable area under the curves (0.69, 0.68 and 0.68, respectively), whereas PSS had a lower AUC (0.60). Responsiveness was greatest for mDAVID (Cohen’s d 0.76 (95% CI 0.30 to 1.20)), followed by mSDAS (0.61 (0.13 to 1.1)), SAS (0.46 (−0.01 to 0.90)) and PSS (0.22 (−0.30 to 0.68)). Longitudinal sensitivity to change, quantified by marginal R², was highest for mDAVID (0.65 (95% CI 0.59 to 0.70)), followed by mSDAS (0.61 (0.55 to 0.67)), PSS (0.61 (0.54 to 0.67)) and SAS (0.55 (0.45 to 0.64)). Sensitivity analyses using complete cases yielded similar results. Conclusion: mDAVID and mSDAS demonstrated the most favourable and largely comparable performance profiles across the evaluated metrics, with mDAVID showing greater responsiveness and mSDAS demonstrating a stronger correlation with the articular disease domain. Trial registration number: ISRCTN86135778 .

Reviews; Authors: S.M. Petzinna, C.-J. Bauer, V.S. Schäfer

Background: Assessing disease activity in giant cell arteritis (GCA) remains challenging, as existing clinical, laboratory and imaging biomarkers lack specificity. This proof-of-concept study explored the diagnostic potential of vascular adhesion protein-1 (VAP-1) targeting [ ⁶⁸ Ga]Ga-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) DOTA-sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) positron emission tomography-CT (PET/CT) as an inflammation-specific molecular imaging biomarker in newly diagnosed and relapsing GCA. Methods: Patients with newly diagnosed GCA underwent [ ⁶⁸ Ga]Ga-DOTA-Siglec-9 PET/CT and vascular ultrasound. Tracer uptake (SUVmean/SUVmax) was quantified in aortic, supra-aortic and extravascular (shoulder/hip) regions and compared with relapsing patients. Levels of soluble VAP-1 (sVAP-1) and matrix metalloproteinase (MMP)2/MMP3/MMP9 were measured in patients and controls as potential biomarkers related to vascular inflammation. Results: Eight patients with newly diagnosed GCA were compared with eight relapsing patients, alongside eight controls. Imaging revealed a positive association between ultrasound-assessed subclavian artery intima-media thickness and tracer uptake (r=0.67, p=0.035). Prednisolone exposure was inversely associated with vascular uptake across various vascular regions, with SUVmean showing a stronger overall negative association than SUVmax (SUVmean r=–0.51, p=0.043; SUVmax r=–0.62, p=0.010). Levels of sVAP-1 were reduced in newly diagnosed GCA compared with relapsing patients (p=0.0145) and controls (p=0.0446), and inversely associated with MMP2 (r=–0.56, p=0.037) and MMP9 (r=–0.47, p=0.089). Notably, MMP2 and MMP3 were negatively associated with vascular uptake (eg, aortic arch: r=–0.59, p=0.027). Conclusions: This first-in-human study demonstrates that [ ⁶⁸ Ga]Ga-DOTA-Siglec-9 PET/CT detects vascular inflammation in GCA and shows attenuation with prednisolone exposure. Reduced sVAP-1 levels and inverse associations between MMP2/MMP3 and tracer uptake support a functional VAP-1/MMP axis underlying the imaging signal. Our findings further position [ ⁶⁸ Ga]Ga-DOTA-Siglec-9 PET/CT as a promising potential molecular imaging biomarker in GCA.

Objectives: To longitudinally assess ocular involvement in newly diagnosed giant cell arteritis (GCA) patients by evaluating changes in transorbital ultrasonography (TOS) parameters and their association with systemic vascular inflammation and treatment response. Methods: In this prospective cohort study, newly diagnosed GCA patients underwent serial TOS assessments of the central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)] and optic nerve diameter (OND) at three-monthly intervals for 12 months. Vascular ultrasonography and calculation of OMERACT Giant Cell Arteritis Ultrasonography (OGUS) Score was conducted. Longitudinal changes and associations were analysed using linear mixed-effects models, accounting for repeated measurements within patients. Results: Thirty-six GCA patients were enrolled. At baseline, 17 (47.2%) patients reported visual symptoms. Compared with baseline, PSV significantly decreased at three (β = −0.81 cm/s, P = 0.046) and nine (β = −0.93 cm/s, P = 0.029) months. OND decreased at three (β = −0.30 mm, P = 0.020) and 12 (β = −0.35 mm, P = 0.008) months, with a consistent trend over follow-up (β = −0.07, P = 0.024). Symptomatic eyes displayed significantly higher PSV (β = 0.96, P = 0.017) and EDV (β = 0.34, P = 0.037) over disease course. Baseline pathological vessel count and OGUS Score were negatively associated with PSV (β = −0.43, P = 0.031; β = −3.15, P = 0.055) and EDV (β = −0.15, P = 0.022; β = −1.45, P = 0.007) and positively associated with OND (β = 0.15, P = 0.006; β = 0.94, P = 0.040). During disease course, significant associations with pathological vessel count and OGUS Score were noted for EDV (β = −0.04, P = 0.024; β = −0.77, P = 0.005) and OND (β = 0.05, P < 0.001; β = 0.72, P < 0.001). Conclusions: Utilizing TOS, we demonstrated progressive decrease in retinal artery flow and OND, indicating ongoing impairment in retinal vascular supply and potential optic nerve atrophy despite clinical improvement post-treatment. Our findings suggest that intracranial vascular changes in GCA may respond less effectively to treatment than extracranial vessels and support a shared pathophysiological mechanism in GCA.

Objectives: To evaluate the diagnostic utility of optical coherence tomography angiography (OCTA)-derived biomarkers in patients with giant cell arteritis (GCA) and to advance the pathophysiological understanding of disease-related microvascular alterations and their association with vascular manifestation. Methods: Newly diagnosed, untreated GCA patients and healthy controls were assessed using OCTA of the optic nerve head (ONH). Skeletonised and binarised vessel densities were quantified in retinal vascular plexus and in the choriocapillaris in concentric rings around the ONH (0.5/1.0 mm diameter). Associations with clinical data, vascular ultrasound including Outcome Measures in Rheumatology Giant Cell Arteritis Ultrasonography Score (OGUS) and large-vessel involvement were evaluated using correlation and multivariable regression analyses. Results: A total of 60 GCA patients and 69 healthy controls were prospectively enrolled. Reduced vessel density in the outer ring (1 mm) of the superficial retinal plexus was the strongest OCTA-derived discriminator of GCA (r=0.28, p=0.001), independent of visual symptoms. Multivariable regression identified lower superficial plexus density as significantly associated with GCA (β=–0.22, p=0.015). Calculated OGUS was positively associated with OCTA alterations (ρ=0.28, p=0.03), while aortic involvement was inversely associated (ρ=–0.32, p=0.02). Age was the only independent predictor of visual symptoms (β=0.173, p=0.013). Conclusions: Our study reveals microvascular alterations in GCA, even in the absence of visual symptoms. Vessel density reduction in the superficial peripapillary plexus may serve as an early biomarker of retinal hypoperfusion. The inverse association with aortic involvement supports the concept of distinct immunophenotypes in GCA.