Application of MRI for Musculoskeletal Involvement in SLE (RMNLES)

Application of MRI for Inflammatory Musculoskeletal Involvement in Systemic Lupus Erithematosus (SLE)

Articular involvement can reach up to 95% within the chronic multisystemic manifestations of SLE (1). Originally, a non-erosive pattern of articular inflammation was described, but the emergence of more sensitive imaging techniques, such as MRI (2, 3), show synovitis, erosions (hand: 47-48%, carpus 82-84% in SLE; and hand: 18%, carpus 97% in healthy individuals), bone oedema (hand: 4-5%, carpus 13-16% in SLE; and 0% in healthy individuals) and tenosynovitis (hand 47%, carpus 79%; not evaluated in healthy individuals) in patients with SLE (4, 5). Nowadays, a specific validated pattern of articular involvement associated with this disease does not yet exist, although it has begun to be studied. This research tries to evaluate the presence, frequency and distribution of inflammatory articular manifestations in SLE (erosions, bone oedema, synovitis or tenosynovitis) using MRI (6), with the objective of trying to establish a specific pattern for this disease, if it exists, that can shorten the diagnostic process. Moreover, it tries to characterise, if they exist, clinical differences between various patient groups according to their articular involvement.

Study Overview

• Status: Unknown
• Conditions: Hand Rheumatism; Systemic Lupus Erythematosus Arthritis
• Intervention / Treatment: Procedure: Blood test

Detailed Description

BACKGROUND AND RATIONALE

• Nowadays no valid classification system for SLE-related arthritis/tenosynovitis exists.
• Data are not sufficient to establish an SLE-specific pattern of inflammatory involvement, similar to the pattern known for other inflammatory diseases such as rheumatoid arthritis (RA).
• Erosive arthritis associated with SLE has been typically related to patients that meet the criteria both for SLE and RA - syndrome known as Rhupus; but only a few data exist that classify erosive involvement of articular inflammation of pure SLE.
• No research exists that links the articular inflammatory pathology associated with SLE with its effect on quality of life (degree of fatigue and HAQ) or with the rest of manifestations and comorbidities associated with SLE.
• Being able to predict the development of SLE-related arthritis/tenosynovitis would be very useful when it comes to establishing the clinical management, treatment and prognosis of patients with SLE.

OBJECTIVES

• GENERAL:

  - To describe the kind of inflammatory articular involvement (synovitis/erosions/bone oedema/tenosynovitis) (6,7) and its frequency in patients affected by pure SLE (excluding Rhupus, mixed connective tissue disease, overlap syndromes).

• SPECIFIC:

  • To propose, if possible, an SLE-specific typical pattern of articular involvement.
  • To establish clinical and serological differences (extra-articular manifestations, autoimmunity, treatment received, comorbidities and quality of life) according to the type of inflammatory articular involvement and in comparison to healthy individuals.
  • To evaluate the possible link between SLEDAI/SLICC scores and the involvement using MRI.

HYPOTHESIS

• Patients with SLE have a specific inflammatory articular disease.
• A SLE-specific pattern of articular involvement exists.
• There are clinical and serological differences depending on the different patterns of articular involvement in SLE.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Patricia Corzo, MD; Phone Number: +34655057358; Email: pcorzoreumatologia@gmail.com
• Study Contact Backup: Name: Tarek Carlos Salman, PhD; Email: tareto4@gmail.com

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Recruiting
    • Hospital del Mar
    • Contact: PAtricia Corzo Salman, MD; Phone Number: +34655057358; Email: pcorzoreumatologia@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients affected by SLE (1982 revised criteria) with scheduled visits to the SLE specialized medical office at Hospital del Mar:

  • (pain+ / synovitis +): SLE patients with inflammatory pain and synovitis determined by the practitioner during physical examination of radius and ulna carpal joint and/or carpus and/or metacarpophalangeal joint and/or IP . Defining synovitis as pain and inflammation and/or deformity (present or existing over the past year) included in the clinical history
  • (pain + / synovitis -) SLE patients with inflammatory pain without determined synovitis . Current (or over the past year) pain in radius and ulna carpal joint and/or carpus and/or metacarpophalangeal joint and/or IP, with no synovitis
• (pain - / synovitis -) SLE patients without inflammatory pain with normal physical examination currently or over the past year
• Control patients, without SLE nor immediate relatives affected by systemic inflammatory diseases, who lack articular pain and have blood test with no elevation APR or autoimmunity +)

Exclusion Criteria:

• Jaccoud's arthropaty
• RF + and/or ACPA +
• Incomplete SLE, MCTD, overlap syndromes
• Hand surgery
• Current neoplasia
• Non-rheumatoid systemic autoimmune diseases
• Contraindication for MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: pain+ / synovitis +; SLE patients with inflammatory pain and synovitis determined by the practitioner during physical examination of radius and ulna carpal joint and/or carpus and/or metacarpophalangeal joint and/or IP. Defining synovitis as pain and inflammation and/or deformity (present or existing over the past year) included in the clinical history	Procedure: Blood test; Carpus and fingers of non-dominating hand MRI with gadolinium contrast; Other Names: hand MRI
Active Comparator: pain + / synovitis -; SLE patients with inflammatory pain without determined synovitis. Current (or over the past year) pain in radius and ulna carpal joint and/or carpus and/or metacarpophalangeal joint and/or IP, with no synovitis	Procedure: Blood test; Carpus and fingers of non-dominating hand MRI with gadolinium contrast; Other Names: hand MRI
Active Comparator: pain - / synovitis -; SLE patients without inflammatory pain with normal physical examination currently or over the past year	Procedure: Blood test; Carpus and fingers of non-dominating hand MRI with gadolinium contrast; Other Names: hand MRI
Placebo Comparator: healthy; control patients (healthy participants: no pain, no SLE, no family affected by systemic inflammatory disease, a blood test with no elevation APR or autoimmunity +)	Procedure: Blood test; Carpus and fingers of non-dominating hand MRI with gadolinium contrast; Other Names: hand MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI inflamatory changes	synovitis, erosions, bone oedema, tenosynovitis	1 to 2 months after clinical assesment
SLE activity scale	Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Measures last 10 days disease activity (rating (Y/N) 24 items related to specific manifestations on 9 organs) From 0 (best) to 105 (worst)	at clinical assesment
SLE treatments used	Number (n and %) of participants using any approved treatments for SLE used since diagnosis	at clinical assesment
Fatigue	Fatigue Severity Scale (FSS-9) Results from 9 (best) to 63 (worst): rating 9 items ranging from 1(best) to 7 (worst)	2 weeks before the performance of MRI
Quality of life scale	modified health assessment questionnaire (MHAQ): Results from 0 (best) to 3 (worst): rating 9 items from 0 (best) to 3 (worst) (results given divided by 8)	2 weeks before the performance of MRI
SLE damage scale	Systemic Lupus International Collaborating Clinics (SLICC) damage index: Irreversible damage rated by: 42 items related to 12 organs: 0 (absent-best)/1 (present-worst), some of them can count 2 or 3 (worst) if recidivant. From 0 (best) to 46 (worst)	at clinical assesment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serological markers of disease activity: antinuclear antibodies (ANA)	ANA (dilution): given by titters (average titters comapred between groups)	6 months prior to 6 months after assesment
Systemic SLE manifestations	presence of renal, lung, skin, neurological, haematological manifestations since diagnostic (Yes/No)	at clinical assesment
Hand pain visual analogue scale (VAS)	VAS 0 (none) to 10 (maximum)	at clinical assesment
Serological markers of disease activity: Anti-double stranded DNA antibody (DNAds)	Titters DNAds (UI/ml)	6 months prior to 6 months after assesment (the closest to MRI)
Serological markers of disease activity: Anti-Smith antibodies (Sm)	Presence of Sm (Yes/No)	6 months prior to 6 months after assesment (the closest to MRI)
Serological markers of disease activity: complement 3 (C3)	titters C3 (mg/dL)	6 months prior to 6 months after assesment (the closest to MRI)
Serological markers of disease activity: complement 4 (C4)	titters C4 (mg/dl)	6 months prior to 6 months after assesment (the closest to MRI)
Serological markers of disease activity: erythrocyte sedimentation rate (ESR)	ESR (mm/h)	6 months prior to 6 months after assesment (the closest to MRI)
Serological markers of disease activity: C reactive protein (CRP)	CRP (mg/dl)	6 months prior to 6 months after assesment (the closest to MRI)
Serological markers of disease activity:white cell blood count (WCBC)	WCBC: cellsx10E9/L	6 months prior to 6 months after assesment (the closest to MRI)

Collaborators and Investigators

• Sponsor: Hospital del Mar
• Investigators: Principal Investigator: PAtricia corzo, MD, Hospital del Mar

Publications and helpful links

General Publications

• Ball EM, Bell AL. Lupus arthritis--do we have a clinically useful classification? Rheumatology (Oxford). 2012 May;51(5):771-9. doi: 10.1093/rheumatology/ker381. Epub 2011 Dec 15.
• Mosca M, Tani C, Carli L, Vagnani S, Possemato N, Delle Sedie A, Cagnoni M, D'Aniello D, Riente L, Caramella D, Bombardieri S. The role of imaging in the evaluation of joint involvement in 102 consecutive patients with systemic lupus erythematosus. Autoimmun Rev. 2015 Jan;14(1):10-5. doi: 10.1016/j.autrev.2014.08.007. Epub 2014 Aug 23.
• Tani C, D'Aniello D, Possemato N, Delle Sedie A, Caramella D, Bombardieri S, Mosca M. MRI pattern of arthritis in systemic lupus erythematosus: a comparative study with rheumatoid arthritis and healthy subjects. Skeletal Radiol. 2015 Feb;44(2):261-6. doi: 10.1007/s00256-014-2033-0. Epub 2014 Oct 24. Erratum In: Skeletal Radiol. 2015 Feb;44(2):267. Chiara, Tani [corrected to Tani, Chiara]; Dario, D'aniello [corrected to D'Aniello, Dario]; Niccolo, Possemato [corrected to Possemato, Niccolo]; Andrea, Delle Sedie [corrected to Delle Sedie, Andrea]; Davide, Caramella [corrected to Caramella, Davide].
• Boutry N, Hachulla E, Flipo RM, Cortet B, Cotten A. MR imaging findings in hands in early rheumatoid arthritis: comparison with those in systemic lupus erythematosus and primary Sjogren syndrome. Radiology. 2005 Aug;236(2):593-600. doi: 10.1148/radiol.2361040844. Epub 2005 Jun 21.
• Ostergaard M, Peterfy C, Conaghan P, McQueen F, Bird P, Ejbjerg B, Shnier R, O'Connor P, Klarlund M, Emery P, Genant H, Lassere M, Edmonds J. OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Core set of MRI acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system. J Rheumatol. 2003 Jun;30(6):1385-6. Erratum In: J Rheumatol. 2004 Jan;31(1):198.
• Haavardsholm EA, Ostergaard M, Ejbjerg BJ, Kvan NP, Kvien TK. Introduction of a novel magnetic resonance imaging tenosynovitis score for rheumatoid arthritis: reliability in a multireader longitudinal study. Ann Rheum Dis. 2007 Sep;66(9):1216-20. doi: 10.1136/ard.2006.068361. Epub 2007 Mar 28.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): May 1, 2020

Study Registration Dates

• First Submitted: July 23, 2019
• First Submitted That Met QC Criteria: July 24, 2019
• First Posted (Actual): July 29, 2019

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 29, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Rheumatic Diseases
• Other Study ID Numbers: RMNLES

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: IPD will be used for PhD investigations. IPD will not be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No