Evaluation of Circulating Neutrophils in Antisynthetase Syndrome (NEUTROSAS2)

Evaluation of Circulating Neutrophils in Antisynthetase Syndrome: a Multicenter Retrospective Study

Antisynthetase syndrome (ASyS) is a rare and heteregeneous overlapping connective tissue disease, characterized by myositis, interstitial lung disease (ILD), joint involvement, Raynaud's phenomenon and cutaneous manifestations ("mechanic's hands"). Over 50% of patients develop ILD, which is the leading cause of death.

The role of neutrophils - innate immune cells involved in inflammatory processes and induced in particular by cytokines of the Th17 pathway - during AS is unknown. Direct pathogenic role of neutrophils has been described during idiopathic inflammatory myopathies, with an increase of netosis correlated with disease activity and muscle damage. During ASyS, a higher number of alveolar neutrophils has been observed in patients with rapidly progressive ILD.

There are few data on the specific evaluation of circulating neutrophils in ASyS. Investigators suppose that circulating neutrophils level could represent a simple and accessible severity biomarker in patients with ASyS.

The main objective is to evaluate the diagnostic performance of the circulating neutrophils level (> 7000/mm3) at diagnosis on ASyS severity.

The secondary objectives are:

• to define a threshold for circulating neutrophils levels at diagnosis allowing to predict ASyS severity and to assess the diagnostic performance of this threshold.
• to study the correlation between the level of circulating neutrophils and ASyS severity at diagnosis of the disease.
• to compare the circulating neutrophils level at ASyS diagnosis and after 1 year of treatment.
• to compare patients characteristics according to ASyS severity at diagnosis.
• to compare BAL fluid neutrophils level according to ILD severity at ASyS diagnosis in patients with ILD.

Study Overview

• Status: Not yet recruiting
• Conditions: Antisynthetase Syndrome
• Intervention / Treatment: Diagnostic test: circulating neutrophils

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Paul Decker, MD; Phone Number: +33383157240; Email: p.decker@chru-nancy.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients with ASyS diagnosis between January 2010 and December 2022

Description

Inclusion Criteria:

• Patients with ASyS diagnosis according to Connors criteria

Exclusion Criteria:

• Active infection at ASyS diagnosis
• Evolutive cancer at ASyS diagnosis
• Corticosteroid therapy initiation before circulating neutrophils evaluation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ASyS patients; Patients with antisynthetase syndrome	Diagnostic test: circulating neutrophils; evaluation of circulating neutrophils level

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
circulating neutrophils level > 7000/mm3		baseline (J0)
number of patients with global severity	global severity defined as presence of severe ILD (PaO2 < 600 mmHg or rapidly progressive ILD), and/or presence of severe myositis (bedrest, or MMT8 score < 30, or MRC muscle testing < 3/5, or swallowing disorers, or dysphagia) and/or presence of myocarditis on cardiac MRI	baseline (J0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
circulating neutrophils level		baseline (J0)
FVC	FVC percentage	baseline (J0)
DLCO	DLCO percentage	baseline (J0)
CK level		baseline (J0)
circulating neutrophils level		12 months
BAL fluid neutrophils level		baseline (J0)
grade of MRC muscle testing		baseline (J0)

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: Paul Decker, MD, CHU Nancy

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: August 4, 2023
• First Submitted That Met QC Criteria: August 4, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Disease; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Syndrome; Myositis
• Other Study ID Numbers: 2023PI083

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