TArget Trial Emulation Comparing Effectiveness of Tocilizumab vs Methotrexate In Corticosteroid-Treated GCA Patients (TACTIC-GCA)

Comparative Effect of Tocilizumab Versus Methotrexate on Major Adverse Cardiovascular Events in Giant Cell Arteritis: A Nationwide Target Trial Emulation Using the French SNDS

This nationwide observational study emulates a target trial to compare the effect of tocilizumab versus methotrexate initiation on major adverse cardiovascular events (MACE) in patients with incident giant cell arteritis using the French National Health Data System (SNDS).

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Giant Cell Arteritis (GCA)

Detailed Description

Study Design and Data Source This study is a retrospective nationwide cohort study using the SNDS database covering approximately 99% of the French population. We emulated a hypothetical randomized trial comparing two treatment strategies: initiation of tocilizumab versus methotrexate within 6 months after hospital discharge for incident giant cell arteritis. Eligible patients aged ≥50 years hospitalized for incident GCA between 2012 and 2024 were included.

Statistical Analysis A clone-censor-weight approach was used to account for treatment initiation timing and avoid immortal time bias. Inverse probability of censoring weights were applied to adjust for informative censoring. Treatment effects were estimated using weighted Kaplan-Meier methods and Cox proportional hazards models.

Outcomes The primary outcome was the occurrence of major adverse cardiovascular events (MACE), defined as myocardial infarction, ischemic stroke, or all-cause death. Secondary outcomes included individual cardiovascular components, aortic events, and major vascular relapse.

Regulatory Compliance This study was conducted using the SNDS through the permanent access granted to Assistance Publique - Hôpitaux de Paris (AP-HP), in accordance with French Decree No. 2016-1871 and French Public Health Code (Art. R. 1461-13 and 14). The study was registered in the AP-HP internal registry of research projects before initiation. In compliance with the GDPR and French regulations, individual informed consent was not required as all data were fully anonymized

• Study Type: Observational
• Enrollment (Actual): 1667

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • APHP_ Hôpital Pitié-Salpêtrière
  • Paris, France, 75012
    • APHP_ Hôpital Saint-Antoine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients aged ≥50 years hospitalized for incident giant cell arteritis in France identified from the SNDS database.

Description

Inclusion Criteria:

• Age ≥50 years Incident hospitalization for giant cell arteritis Initiation of tocilizumab or methotrexate within 6 months Received systemic corticosteroids ≥20 mg/day within 30 days following hospital discharge

Exclusion Criteria:

• Prior use of tocilizumab or methotrexate Age >90 years Length of stay >30 days Not discharged home Prior aortic disease or vascular imaging within 2 years Initiation of both treatments during grace period

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Tocilizumab group; Patients initiating tocilizumab within 6 months after discharge for incident GCA.
Methotrexate group; Patients initiating methotrexate within 6 months after discharge for incident GCA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Cardiovascular Events (MACE)	Major Adverse Cardiovascular Events (MACE) Composite of myocardial infarction, ischemic stroke, or all-cause death	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary events	Coronary events (myocardial infarction or unstable angina)	2 years
Ischemic stroke	Ischemic stroke assessed at 2 years	2 years
All-cause mortality	All-cause mortality assessed at 2 years	2 years
Aortic events	Aortic events (aneurysm or dissection)	2 years
Major vascular relapse	Major vascular relapse assessed at 2 years	2 years
Lower limb revascularization	7. Lower limb revascularization assessed at 2 years	2 years
Anterior ischemic optic neuropathy (AION)	Anterior ischemic optic neuropathy (AION) assessed at 2 years	2 years
Peripheral artery disease events	Peripheral artery disease events assessed at 2 years	2 years
Cancer incidence	Cancer incidence at 2 years	2 years

Collaborators and Investigators

• Sponsor: Groupe français d'étude des Maladies Inflammatoires de loeil

Publications and helpful links

General Publications

• Tuppin P, Rudant J, Constantinou P, Gastaldi-Menager C, Rachas A, de Roquefeuil L, Maura G, Caillol H, Tajahmady A, Coste J, Gissot C, Weill A, Fagot-Campagna A. Value of a national administrative database to guide public decisions: From the systeme national d'information interregimes de l'Assurance Maladie (SNIIRAM) to the systeme national des donnees de sante (SNDS) in France. Rev Epidemiol Sante Publique. 2017 Oct;65 Suppl 4:S149-S167. doi: 10.1016/j.respe.2017.05.004. Epub 2017 Jul 27.
• Scailteux LM, Droitcourt C, Balusson F, Nowak E, Kerbrat S, Dupuy A, Drezen E, Happe A, Oger E. French administrative health care database (SNDS): The value of its enrichment. Therapie. 2019 Apr;74(2):215-223. doi: 10.1016/j.therap.2018.09.072. Epub 2018 Oct 25.
• Hernan MA, Wang W, Leaf DE. Target Trial Emulation: A Framework for Causal Inference From Observational Data. JAMA. 2022 Dec 27;328(24):2446-2447. doi: 10.1001/jama.2022.21383.
• Guedon AF, Espitia O, Beydon M, Ghrenassia E, Mirault T, Messas E, Tubach F, Seror R, Boccara F, Cohen A, Frikke-Schmidt R, Nordestgaard BG, Dellal A, Fain O, Mekinian A, Carrat F. Cardiovascular risk among Giant cells arteritis patients. Eur J Prev Cardiol. 2026 Jan 14:zwag034. doi: 10.1093/eurjpc/zwag034. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Skin Diseases; Skin Diseases, Vascular; Vasculitis; Vasculitis, Central Nervous System; Arteritis; Skin and Connective Tissue Diseases; Cardiovascular Diseases; Giant Cell Arteritis
• Other Study ID Numbers: TACTIC-GCA-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No