START – Molecular stratification of patients with giant cell arteritis to tailor glucocorticoid and tocilizumab therapy

Concept

The present research aims to develop and validate biomarkers whose quantification in temporal artery biopsies (TABs) might predict response to glucocorticoids and tocilizumab in patients with giant cell arteritis (GCA) and to stratify patients according to molecular signatures in TABs. Glucocorticoids are the standard of care in GCA but about 40% of patients relapse when glucocorticoids are tapered. Tocilizumab plus glucocorticoids has recently been proven effective at increasing the percentage of GCA patients in remission and sparing glucocorticoids.

Facts and figures

Project lead
N Pipitone
Azienda Unità Sanitaria Locale
nicolo.piptone@ausl.re.it
2018 - 2021
FOREUM research grant: € 600.000

Meet the team

N Pipitone
Azienda Unità Sanitaria Locale
S Croci
Azienda Unità Sanitaria Locale
F Ciccia
University of Palermo
R Alessandro
University of Palermo
S Fontana
University of Palermo
M Gonzalez-Gay
Hospital Universitario Marqués de Valdecilla
R Lopez-Meijas
Hospital Universitario Marqués de Valdecilla
S Castaneda
Hospital La Princesa
J Martin
Institute of Parasitology and Biomedicine López-Neyra
P Liò
University of Cambridge
D Saadoun
Pitie-Salpetriere Hospital
P Villiger
University Hospital Bern
D Conti
Associazione Malati Reumatici Emilia Romagna
J Baquero
Foro Español de Pacientes

Objectives

  1. Identification of biomarkers in TABs whose quantification may allow to predict at diagnosis patients’ response to glucocorticoids and tocilizumab.
  2. Stratification of GCA patients according to molecular signatures in TABs and correlation of such signatures to the clinical characteristics of patients.    
  3. Validation of the potential predictors and signatures.

The long-term objective is to create the basis for a therapeutic approach in patients with GCA, tailored to molecular characteristics in TABs at diagnosis, aiding physicians to achieve the best outcome in each patients (maximum efficacy with minimal adverse effects) in the shortest time.
 

Patient voice

One Italian (AMRER) and two Spanish (FEP and LIRE) associations of patients are involved as PRPs. Patient associations in France and Switzerland will be further involved.

EULAR guidelines for PRP inclusion have been followed. We have discussed the design of the project and the burden for patients with the PRPs integrating their feedback. PRPs will be involved in all phases of the project

Interim results

The project started on the 3rd December 2018.

3 patients have been recruited by the Unit of the PI at Reggio Emilia. To date only 2/6 clinical centers have received the approval by the local Ethical Committees.

Brochures about GCA and the project have been prepared with patient research partners (PRPs).
RNA/DNA/proteins have been extracted from 6 TABs (retrospective cohort of patients) to check the RNA sequencing, DNA methylation and SWATH-MS profiling.