Lupus Arthritis: Muscoloskeletal Ultrasound as Clinical Outcome of Peripheral Blood and Synovial Deep Phenotyping

NCT ID: NCT07102238

Last Updated: 2025-08-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 269 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-10
• Study Completion Date: 2028-08-01

Brief Summary

Musculoskeletal involvement, defined as arthritis/arthralgia, is the most common manifestation of patients with systemic lupus erythematosus (SLE). It accounts for decreased quality of life and can lead to unemployment and disability.

Lupus arthritis is divided into non-erosive, with up to 80% of the cases, erosive, also known as Rhupus, with up to 5% of cases, and deforming, or Jaccoud's arthropathy which can involve up to 15% of the patients. Initially, these 3 forms can present similarly, therefore identifying early on their specific characteristics, can guide better treatments and improve outcomes.

Muscoloskeletal ultrasound (MSK-US) is an established modality to diagnose and investigate joint involvement in inflammatory arthropathies. While for these conditions, well-defined MSK-US approaches exist, much less, if any, for SLE.

The research hypothesis is that a longitudinal standardized prospective MSK-US evaluation coupled with deep phenotyping in patients with SLE peripheral musculoskeletal involvement, will allow us to:

1. better define the systemic nature of this manifestation and

2. yield novel biomarkers that accurately capture this important feature of SLE. In this monocenter study consecutive SLE patients with inflammatory MSK symptoms will recruited and followed prospectively. Patients will undergo MSK ultrasound, blood sample collection, synovial biopsy, for histological assessment. A subgroup of the study cohort will have synovial, Peripheral Blood Mononuclear Cells (PBMCs), serum and omic analysis. Patients will be followed for at least 6 months and up to 18 months with clinical and US evaluation.

Aims and methods

The following two aims are proposed:

1. to define the prevalence and evolution of MSK involvement in SLE patients with inflammatory arthralgia using a standardized US evaluation according with the Outcome Measures in Rheumatology (OMERACT) definition and scoring system In this Aim, a systematic characterization of joint, tendons and enthesis status will be performed through a clinical and US evaluation in order to demonstrate the role of US as an objective tool to better characterize MSK involvement in SLE patients. A MSK-US assessment will be conducted at the beginning and subsequently at each defined time table for all patients.

2. To investigate lupus arthritis with MSK-US, multi-omics technologies including single cell RNA sequencing and proteomics, with the aim to characterize disease activity.

For this Aim, blood and synovial multi-omics analysis will be performed exclusively in a subgroup of 10 SLE recruited patients. A US-guided synovial tissue biopsy will be performed for all patients enrolled in the study, regardless of multi-omics inclusion.

Patients will be longitudinally evaluated to identify clinical articular and systemic flares. The baseline US evaluation and the multi-omics approach will be correlated with the longitudinal manifestations to identify possible biomarkers of flares, both at the joint and systemic levels.

Expected results:

The combined achievement of the above-mentioned aims will address the need to standardize the MSK-US approach and pathogenic mechanisms via biomarkers' discovery of lupus arthritis, a yet still poorly understood SLE manifestation.

expectations:

• To enhance the characterization of joint involvement by reducing the heterogeneity associated with clinical examination through a standardized US evaluation.
• To identify systemic and synovial disease biomarkers in SLE patients that can predict different joint patterns, systemic manifestations and response to therapy through multi-omics technologies.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

SLE with muscoloskeletal involvement

Consecutive patients with MSK symptoms will be recruited and observed over time. Each enrolled patient will be asked for past and current medical history and treatment. Visits will be scheduled at baseline, at months 3 and 6, then every 6 months up to 18 months, and subsequently according to routine clinical practice. Clinical, laboratory and ultrasound assessments will be conducted at each visit.

Each patient will be followed for at least 6 months.Important confounding factors such as immune suppression and short/long-term use of NSAIDs at the time of MSK-US will be taken into account. At baseline, a synovial biopsy will be performed at the joint affected by the inflammatory process, and blood samples will be collected.

Group Type: EXPERIMENTAL

muscoloskeletal ultrasound and synovial biopsy

Intervention Type: PROCEDURE

Use of a standardized US evaluation according with OMERACT definition and scoring system; Synovial biopsy; To identify systemic and synovial disease biomarkers in SLE patients that can predict different joint patterns, systemic manifestations and response to therapy through multi-omics technologies.

other connective tissue diseases with muscoloskeletal involvement

Consecutive patients with MSK symptoms will be recruited and observed over time. Each enrolled patient will be asked for past and current medical history and treatment.Clinical, laboratory and ultrasound assessments will be conducted at baseline.

Important confounding factors such as immune suppression and short/long-term use of NSAIDs at the time of MSK-US will be taken into account.

At baseline, a synovial biopsy will be performed at the joint affected by the inflammatory process, and blood samples will be collected.

DAS28, Physician Global Assessment (PGA), Spondylarthritis Research Consortium of Canada (SPARCC) Enthesitis index, Swollen Joint counts (44 or 66) tender joints count (44-66), Widespread Pain Index/Symptom Severity Scale (WPI/SSS) will be collected at each visit. Patients will be treated according to international recommendations and the treating rheumatologist's decision.

Group Type: EXPERIMENTAL

muscoloskeletal ultrasound and synovial biopsy

Intervention Type: PROCEDURE

Use of a standardized US evaluation according with OMERACT definition and scoring system; Synovial biopsy; To identify systemic and synovial disease biomarkers in SLE patients that can predict different joint patterns, systemic manifestations and response to therapy through multi-omics technologies.

Interventions

muscoloskeletal ultrasound and synovial biopsy

Use of a standardized US evaluation according with OMERACT definition and scoring system; Synovial biopsy; To identify systemic and synovial disease biomarkers in SLE patients that can predict different joint patterns, systemic manifestations and response to therapy through multi-omics technologies.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of SLE under ACR/EULAR 2019 criteria [8]
• Age between 18 and 75 years
• Must have inflammatory arthralgia, i.e. signs or symptoms deemed due to active SLE according to the investigator, in relation to distribution and typical inflammatory patterns as previously suggested, including joint symptoms lasting more than 6 weeks, morning stiffness lasting ≥60 minutes, and the most severe symptoms occurring at night and early morning.
• Must be capable of providing informed consent

Exclusion Criteria

• Patients with contraindications to synovial biopsy or not accepting to perform the synovial biopsy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

D'Agostino Maria Antonietta

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maria Antonietta D'Agostino

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Universitario A. Gemelli, IRCCS

Locations

Fondazione Policlinico Universitario A. Gemelli IRCCS

Rome, RM, Italy

Countries

Italy

Other Identifiers

7740

Identifier Type: -

Identifier Source: org_study_id