Upadacitinib in Giant Cell Arteritis (GCA) With Active Large-vessel Involvement.

Official title

Prospective Observational Study Evaluating the Efficacy and Safety of Upadacitinib in Giant Cell Arteritis (GCA) With Active Large-vessel Involvement.

Overview

Participants will be followed as part of the usual management of their disease. No modifications will be made (no additional visits, examinations, or questionnaires). The safety and well-being of participants will therefore remain unchanged. The participant will be informed about the study during one of their routine care visits. The information will be provided by the investigator, and the participant's non-opposition to participation in the study will be obtained. The participant will continue to be followed as part of their usual care. Data will then be collected from the participant's medical record (including medical reports, original laboratory test results, imaging reports and medical examinations, and nursing records) for the period of participation in the research, solely for the purpose of meeting the objectives of the research. The data collected will consist of information from the patient's medical record as part of their routine follow-up and will be strictly necessary to address the primary and secondary objectives of the study. The following data will be collected: demographic data (age, sex, weight, height); clinical data (medical history, diagnosed condition, disease activity), treatments, biological data, imaging data, and adverse events. No genetic data will be collected as part of the study. There will be no transfer of data abroad, and no additional questionnaires, examinations, or visits will be added by the research.

Detailed description

This is an observational, multicenter cohort evaluating the safety and efficacy of upadacitinib in patients with giant cell arteritis (GCA). Patient treatment and follow-up will be conducted in accordance with routine clinical care. No additional visits or examinations will be added for the purposes of the study. Participants will be followed as part of the usual management of their disease. No modifications will be made (no additional visits, examinations, or questionnaires). The safety and well-being of participants will therefore remain unchanged.

The participant will be informed about the study during one of their routine care visits. The information will be provided by the investigator, and the participant's non-opposition to participation in the study will be obtained. Patients will then be followed and managed according to routine care (visits and examinations).

Routine care includes:

* A clinical assessment of efficacy and safety at weeks 12, 24, 36, 52, and 104; * Oral prednisone treatment at the initial doses recommended by international and French guidelines, in accordance with routine care.

Treatment with upadacitinib will be initiated at the time of patient inclusion (one 15 mg tablet per day) and will be maintained for 104 weeks. Data will then be collected from the participant's medical record (including medical reports, original laboratory test results, imaging reports and medical examinations, and nursing records) for the period of participation in the research, solely for the purpose of meeting the objectives of the research. Clinical, biological, and radiological efficacy data, as well as treatment safety, will be prospectively analyzed at 3, 6, 12, and 24 months.

Primary outcome measures

• The proportion of patients achieving remission of GCA [Time frame: Week 24.]

Secondary outcome measures (6)

• Cumulative incidence of relapses [Time frame: Weeks 12, 24, 36, 52, and 104;]
• Cumulative incidence of GCA remission according to the EULAR consensus definitions [Time frame: Weeks 12, 36, 52, and 104;]
• Cumulative prednisone dose [Time frame: Weeks 12, 24, 36, 52, and 104;]
• Cumulative incidence of adverse events and serious adverse events [Time frame: Weeks 12, 24, 36, 52, and 104]
• Proportion of aortic inflammatory activity as well as radiological vascular progression (i.e., new aortic dilatation and/or stenosis) [Time frame: Weeks 24, 52, and 104,]
• Cumulative incidence rate of the need for vascular, endovascular, or surgical revascularization procedures due to inflammatory activity [Time frame: Weeks 24, 52, and 104.]

Eligibility criteria

Inclusion criteria

Patients aged over 18 years; Signed informed consent; Affiliation with the French national social security system; Diagnosis of newly diagnosed or relapsing GCA according to the 2022 ACR/EULAR criteria; Active aortitis related to GCA demonstrated by imaging (CT angiography, MR angiography, and/or PET-CT); Indication for treatment with an anti-JAK agent within the scope of the marketing authorization for GCA: failure of, intolerance to, or contraindication to tocilizumab therapy; No contraindication to JAK inhibitors.

Exclusion criteria

• Pregnancy or breastfeeding (for women of childbearing potential, a negative serum pregnancy test will be required); History of severe immunosuppression, HIV infection, hepatitis C virus (HCV), or positive hepatitis B surface antigen (HBsAg); Non-response to or intolerance of a previous anti-JAK treatment; Positive QuantiFERON test (QFT-TB Gold In-Tube) indicating active tuberculosis (latent tuberculosis under treatment for at least 3 weeks may be included); Receipt of live vaccines within the 3 months preceding treatment initiation; History of malignancy within the past 5 years; Severe renal impairment (creatinine clearance < 30 mL/min/1.73 m²); Hepatic dysfunction defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels ≥ 5 times the upper limit of normal;

Abnormal blood counts:

Platelets < 50 × 10³/mm³; Neutropenia < 1,000/mm³; Hemoglobin < 8 g/dL; History of thromboembolic disease; History of severe cardiovascular disease.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 14 centers

• Clinique Axium - Aix-en-provence — Aix-en-Provence
• CHU Caen Normandie — Caen
• CHU de Dijon — Dijon
• CH du Mans — Le Mans
• APHM_Hôpital Nord — Marseille
• APHM_Hôpital La Conception — Marseille
• GHSIF Melun — Melun
• GHI Le Raincy Montfermeil — Montfermeil
• … and 6 more centers

Identifiers

NCT: NCT07354906 · TILT2 · 2025-A02745-44

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗