Takayasu Arteritis (TAK)
Conditions
Brief summary
This is a multicenter prospective observational study aimed at evaluating the role of an ultrasonographic score in monitoring disease activity in patients with Takayasu arteritis (TAK). Patients with active disease, either at new diagnosis or during relapse, will undergo serial vascular US assessments during follow-up according to routine clinical practice at each participating centers. For each patient, an OMERACT-derived US score (OTUS) will be calculated. This score was developed and preliminarily validated in previous phases of a multistep project endorsed by OMERACT (Outcome Measures in Rheumatology), an international initiative focused on the development and validation of outcome measures in rheumatology. The study hypothesis is that this score is sensitive to change over time and can be used to monitor disease activity and predict outcome in patients with TAK.
Detailed description
This is an observational study. The study concerns a diagnostic procedure (vascular US) that is part of normal clinical practice for patients with large-vessel vasculitis (LVV). The decision to perform vascular US in patients with TAK will remain independent from the decision to enroll the patient in the study. No investigational medicinal product or experimental device is involved. The procedure under study is an ultrasonographic scoring system derived from vascular US examinations of selected arterial segments in patients with TAK. Examinations will be performed according to standardized OMERACT protocols, including assessment of the common carotid, subclavian and axillary arteries, and the abdominal aorta. For each patient, an OMERACT-derived OTUS score will be calculated at each assessment. No comparator is mandated; however, clinical disease activity state and results from other imaging modalities (FDG-PET, MRA, CTA), when available as part of routine clinical care, will be collected for exploratory analyses. Study participation will last 24 months, during which patients will undergo serial US examinations at predefined follow-up visits as part of routine clinical monitoring. Vascular US is a non-invasive, radiation-free and contrast-free technique, already employed in standard clinical care and used here exclusively for observational purposes.
Interventions
None listed
Sponsors
IRCCS San Raffaele
Azienda USL Reggio Emilia - IRCCS
University Hospital Padova
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Male and female * Diagnosis of TAK according to the 1990 ACR and/or 2022 ACR/EULAR classification criteria * Active disease, defined as the presence of at least two of the following three domains: * Clinical domain: new onset or worsening of clinical signs and/or symptoms attributable to TAK; * Laboratory domain: elevation of inflammatory markers, defined as ESR and/or CRP above the upper limit of normal according to local laboratory standards, not attributable to causes other than TAK; * Imaging domain: imaging evidence of active vasculitis on modalities other than ultrasound, including FDG-PET, magnetic resonance angiography (MRA), or computed tomography angiography (CTA). * Ability to undergo serial vascular ultrasound assessments during follow-up * Provision of signed informed consent
Exclusion criteria
* Inability or contraindication to undergo vascular US * Severe comorbidities limiting participation or follow-up * Concomitant conditions that may confound ultrasound findings (e.g., significant atherosclerosis requiring intervention, complete occlusion of one of the arterial segments under investigation) * Diagnosis of another rheumatologic disease * Refusal or inability to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in OTUS between active disease and remission in patients with Takayasu arteritis | US performed at baseline, month 1, month 3, month 6, month 12, month 18, month 24. For the primary endpoint only baseline → first remission visit will be analyzed. | Change in OTUS from baseline (active disease) to the first visit at which clinical remission is achieved, as determined by the treating physician (blinded to ultrasound results). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between OTUS changes and clinical/laboratory markers of disease activity in Takayasu arteritis | US performed at baseline, month 1, month 3, month 6, month 12, month 18, month 24. | Correlation between OTUS variation and: (i) ESR/CRP; (ii) clinical disease activity, as assessed by the Physician Global Assessment (PGA) of disease activity (0-10 visual analogue scale) and the National Institutes of Health (NIH) disease activity score for Takayasu arteritis. |
| Agreement between OTUS-based disease activity classification and Physician Global Assessment (PGA) in Takayasu arteritis | US performed at baseline, month 1, month 3, month 6, month 12, month 18, month 24. | Cohen's kappa coefficient measuring agreement between OTUS-based disease activity classification and Physician Global Assessment (PGA) of disease activity, assessed on a 0-10 visual analogue scale. |
| To evaluate the agreement between OTUS-based activity assessment and NIH disease activity score | Baseline, month 1, month 3, month 6, month 12, month 18, month 24 | Cohen's kappa coefficient measuring agreement between OTUS-based disease activity classification and the National Institutes of Health (NIH) disease activity score for Takayasu arteritis (range 0-4, with higher scores indicating more active disease). |
| Hazard ratio for time to relapse per unit increase in baseline OTUS score | US performed at baseline, month 1, month 3, month 6, month 12, month 18, month 24. | Time to disease relapse (months), defined as recurrence of clinical signs and/or symptoms attributable to TAK with or without elevation of inflammatory markers, as judged by the treating physician. The hazard ratio per unit increase in baseline OTUS score will be estimated using Cox proportional-hazards regression. |
| Hazard ratio for time to vascular damage progression per unit increase in baseline OTUS score | US performed at baseline, month 1, month 3, month 6, month 12, month 18, month 24. | Time to vascular damage progression (months), defined as new or worsening stenosis, occlusion, or aneurysm detected on CTA, MRA, or vascular US compared to baseline. The hazard ratio per unit increase in baseline OTUS score will be estimated using Cox proportional-hazards regression. |
| Odds ratio for successful glucocorticoid discontinuation per unit increase in baseline OTUS score | US performed at baseline, month 1, month 3, month 6, month 12, month 18, month 24. | Proportion of patients achieving successful glucocorticoid discontinuation, defined as complete GC tapering without relapse for at least 3 consecutive months. The odds ratio per unit increase in baseline OTUS score will be estimated using logistic regression. |
| Hazard ratio for time to relapse per unit increase in OTUS change from baseline to month 3 | US performed at baseline, month 1, month 3, month 6, month 12, month 18, month 24. | Time to disease relapse (months), defined as recurrence of clinical signs and/or symptoms attributable to TAK with or without elevation of inflammatory markers, as judged by the treating physician. The hazard ratio per unit increase in OTUS change from baseline to month 3 (ΔOTUS) will be estimated using Cox proportional-hazards regression. |
| Hazard ratio for time to vascular damage progression per unit increase in OTUS change from baseline to month 3 | US performed at baseline, month 1, month 3, month 6, month 12, month 18, month 24. | Time to vascular damage progression (months), defined as new or worsening stenosis, occlusion, or aneurysm detected on CTA, MRA, or vascular US compared to baseline. The hazard ratio per unit increase in OTUS change from baseline to month 3 (ΔOTUS) will be estimated using Cox proportional-hazards regression. |
| Odds ratio for successful glucocorticoid discontinuation per unit increase in OTUS change from baseline to month 3 | US performed at baseline, month 1, month 3, month 6, month 12, month 18, month 24. | Proportion of patients achieving successful glucocorticoid discontinuation, defined as complete GC tapering without relapse for at least 3 consecutive months. The odds ratio per unit increase in OTUS change from baseline to month 3 (ΔOTUS) will be estimated using logistic regression. |
| To assess the diagnostic ability of OTUS to detect clinical relapse during follow-up. | US performed at baseline, month 1, month 3, month 6, month 12, month 18, month 24. | Diagnostic performance of OTUS for relapse detection |
| Absolute OTUS score in treatment responders vs non-responders | US performed at baseline, month 1, month 3, month 6, month 12, month 18, month 24. | Absolute OTUS score at each visit compared between clinical responders and non-responders to treatment, defined by physician global assessment. Difference between groups will be assessed using Mann-Whitney U test, with effect size estimation. |
| OTUS change from baseline (ΔOTUS) in treatment responders vs non-responders | US performed at baseline, month 1, month 3, month 6, month 12, month 18, month 24. | Change in OTUS score from baseline to each follow-up visit (ΔOTUS) compared between clinical responders and non-responders to treatment, defined by physician global assessment. Difference between groups will be assessed using Mann-Whitney U test, with effect size estimation. |
Outcome results
None listed