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

Concept

To provide tools to select the likely most effective therapy for each patient with giant cell arteritis (GCA) right from the time of diagnosis.

Facts and figures

Project lead
N Pipitone
Azienda Unità Sanitaria Locale
nicolo.pipitone@ausl.re.it
FOREUM research grant: € 600.000
2018–2023

Meet the team

N Pipitone
Azienda Unità Sanitaria Locale
S Croci
Azienda Unità Sanitaria Locale
F Ciccia
Università della Campania Vanvitelli
R Alessandro
University of Palermo
S Fontana
University of Palermo
M Gonzalez-Gay
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
D Conti
Associazione Malati Reumatici Emilia Romagna
J Baquero
Foro Español de Pacientes
V Romero
Liga Reumatologica Española
L Carmona
Liga Reumatologica Española

Objectives

  • Identification of biomarkers in temporal artery biopsies (TABs) whose quantification may allow to predict at diagnosis patients’ response to glucocorticoids (GCs) and tocilizumab (TCZ).
  • Stratification of GCA patients according to molecular signatures in TABs and correlation of such signatures to the clinical characteristics of patients. 

Patient voice

One Italian (AMRER) and two Spanish (FEP and LIRE) associations of patients are involved as patient research partners (PRPs). The design of the project and the burden for patients have been discussed with the PRPs integrating their feedback. PRPs raised awareness about the disease in the respective associations, prepared leaflets about the disease and the research project and are disseminating information in the association social media.

Interim results

An electronic CRF by the SMARTY Web platform of AUSL-IRCCS was created to securely collect clinical data. 28 patients were recruited: 24 in the GC arm and 4 in the GC + TCZ arm. We analyzed with RNA sequencing and DNA methylation 8 TABs from patients who responded to GC therapy versus 8 TABs from patients who developed relapses during GC therapy. No differentially expressed genes emerged between the two groups while 211 CpGs were found to be differentially methylated (FDR < 0.05 and Δβ > 0.15). LIRE organized an informative event on GCA and polymialgia rheumatica in collaboration with FEP and Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa. AMRER disseminated the project in the news bulletin of the association.

Publications

EULAR Abstracts

2020

  • SAT0338: Contrast-enhanced ultrasonography in the evaluation of myositis

Go to EULAR Abstract Archive

Goals/Milestones

Month 12: Ppatient recruitment for the glucocorticoid study
Month 18: Patient recruitment for the tocilizumab study
Month 30: Completion of patients follow up for the tocilizumab study
Month 33: Definition of predictors of response to therapy
Month 36: Completion of patient recruitment
Month 40: Completion of RNA, protein and DNA methylation profiling in TABs
Month 46: Definition of molecular signatures associated to clinical characteristics
Month 54: Completion of patients follow up, definition of predictors of response to therapy, validation of the candidate biomarkers and signatures