TocILizumab in aorTitis in GCA (TILT)

This is a prospective, observational study involving patients with active aortitis related to GCA.

After verification of the inclusion and exclusion criteria, and signature of the consent form, patients are included in the study. Patients will be followed and managed according to standard of care (visits and exams).

Oral corticosteroids must be at a stable dose for at least 2 weeks prior to the first administration of study drug at D0.

• All patients will receive oral prednisone ≥ 10 mg/day (or oral corticosteroid equivalent) with a maximum of 60 mg/day of prednisone or equivalent.
• A standardized prednisone reduction schedule (see below) will be applied to all groups as long as the disease is inactive, until prednisone is stopped. The aim is to taper off corticosteroids within eight weeks.
• At D0, MSB11456 / 1 injection S/C weekly will be initiated
• Blood samples will be taken every month up to week 52 for assessment of toxicity and inflammation markers.
• Assessment of adverse events will be done routinely at weeks 12, 24, 36, 52 and 104.
• Clinical evaluation will be performed routinely at weeks 12, 24, 36, 52 and 104.
• Targeted imaging studies (angio-CT) will be performed routinely at 6, 12 and 24 months after the start of treatment and if new symptoms appear.
• FDG Pet scan will be performed routinely at 6, 12 and 24 months after the start of treatment
• Angio-CT and FDG Pet scan will be proofread centrally. A standardized prednisone reduction schedule (see below) will be applied to all patients as long as the disease is inactive, until prednisone is stopped :

Baseline prednisone dose Corresponding dose (mg/day) at each week

CG(mg/d) ____60_____50_____40_____30_____25_____20_____15____10____7.5 (at baseline)

60__________W0

50__________W1____W0

40__________W2____W1____W0

30__________W3____W2____W1____W0

25___________ - ____W3____W2____W1____W0

20__________W4____W4____W3____W2____W1____W0

15__________W5____W5____W4____W3____W2____W1____W0

10__________W6____W6____W5____W4____W3____W2____W2____W0

7.5__________ - _____ - ______ - _____W5____W4____W3____W3____W1____W0

5 ___________W7____W7____W6____W6____W5____W4____W4____W2____W2

0 ___________W8____W8____W7____W7____W6____W6____W5____W4____W4

Sample size:

The investigators anticipated a remission rate of 70% at weel 24 based on pooled data from Viliger et al (1) and Stone et al (2). Viliger et al reported 85% of GCA remission at week 12 and week 52 with tocilizumab(1). Stone et al reported 56% of remission of GCA at week 52 under tocilizumab weekly with less than 10% of relpases between week 24 and week 52 (2). A total of 80 patients will ensure estimating the 24-week remission rate with a precision of +/- 11% using an exact 95% confidence intervalgiven the expected 70% remission rate.

Statistical analysis:

Descriptive analyses will be performed with counts and percent for discrete variables and median and interquartile range for continuous variables. The primary endpoint will be described with the 24-week remission proportion point estimate and its exact 95% confidence interval (95%CI) (Clopper Pearson). Secondary endpoints will be described using a similar approach for binary endpoints,continuous endpoints will be decsribed unsing median (IQR) and also mean (SD) with approximate Gaussian 95%CI for the mean.Kaplan Meier estimator or cumulative incidence estimates allowing competing risks when appropriate (i.e. treatment discontinuation due to toxicity), will be used for right-ecensored time to event variables, with 95% confidence intervals.

Inclusion criteria

• Patients ≥18 years
• Signed informed consent
• Affiliation with the French national social security system
• Adequate and effective contraceptive measures
• For women of childbearing age, a negative serum pregnancy test.
• Diagnosis of GCA according to 2022 ACR/EULAR criteria
• Active newly diagnosed or relapsing Aortitis related to GCA proved by imaging (Tep-scan, angio-CT or magnetic resonance imaging angiography)
• No neoplasia
• No contraindication to Tocilizumab

Exclusion criteria

• Pregnancy or breastfeeding ;
• History of severe immunosuppression, HIV or HBsAg positive
• Non response or intolerance to previous therapy with tocilizumab
• Positive QuantiFERON test result (QFT-TBGIn-Tube)
• Have received live vaccines within 3 months prior to the start of the trial
• History of malignancy in the last 5 years
• Severe renal impairment (creatinine clearance <30mL/min/1.73m²)
• Liver dysfunction defined as aspartate transaminase (AST) or alanine transaminase (ALT) levels ≥ 5 at the upper limit of normal
• Blood count abnormality:

• Platelet count < 50 x 10.3/mm3
• Neutropenia < 1000/mm3
• Hemoglobin < 8 g/dl