Assess Structural Damage in Rheumatoid Arthritis Using Biomarkers and Radiography

Rheumatoid Arthritis Clinical Trial

Official title:

Prospective Validation of Soluble Biomarkers as Predictors of Structural Damage in Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01476956
• Other study ID #: RA BIODAM
• Status: Completed
• Start date: October 2011
• Est. completion date: December 31, 2019

Study information

• Verified date: October 2021
• Source: Canadian Research & Education in Arthritis
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Recruited patients will include those about to begin Disease-Modifying Antirheumatic Drug) DMARD therapy or about to change DMARD therapy. Disease activity will be monitored systematically every 3 months by the Disease Activity Score. Changes in standard DMARD and/or anti-Tumor Necrosis Factor α (anti-TNFα) therapy will be made according to specific recommendations for patients receiving these therapies. Biomarker samples will be collected every 3 months and prior to change in DMARD and/or anti-TNF therapy as defined below. A blood sample (40 ml) for serum will be taken for biomarker studies and processed according to the international committee of Outcome Measures in Rheumatology (OMERACT) recommendations for the minimal handling of biomarker samples. A urine sample (20 ml) will also be taken and processed as for serum. Radiography (X-rays) will be conducted every 6 months (baseline, 6, 12, 18, 24 months). Patients will be followed for 2 years.

Description:

Treatment is Disease Activity Score (DAS) driven. Changes in standard DMARD and/or anti-TNFα therapy will be implemented according to 2010 European League against Rheumatism (EULAR) recommendations which state a target of remission (DAS44 <1.6) for patients receiving standard DMARD therapy in the setting of early disease and a target of low disease activity state (LDAS) (DAS44 ≤2.4) for patients receiving anti-TNFα therapy in the setting of established disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 571
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (selected):

• 18 years of age or older
• RA according to the 2010 Rheumatoid Arthritis Classification Criteria
• Joint symptoms for = 3 months prior to screening
• DAS44 > 2.4
• About to start DMARD therapy (methotrexate, salazopyrin, hydroxychloroquine, chloroquine, leflunomide) or
• increased dose of methotrexate by =10 mg weekly to a maximum dose of 25mg weekly (if already receiving >15mg will require add-on DMARD/anti-TNF or switch to alternative DMARD),
• add-on of alternative DMARD,
• switch to alternative DMARD,
• start of first anti-TNFa agent (adalimumab, etanercept, infliximab, certolizumab pegol, golimumab)
• If already on DMARD therapy this has been stable for the 3 months prior to the baseline visit
• If already on systemic steroid, dose must be stable (prednisone = 7.5mg/day) for 1 month prior to the baseline visit
• Patient will be available for follow up for a minimum of 24 months from the baseline visit

Exclusion Criteria (selected):

• Intra-articular steroid injection within 4 weeks prior to the baseline visit
• Prior treatment with anti-TNFa or other biological agent (rituximab, abatacept, tocilizumab)
• Malignancy within past 5 years (other than basal cell carcinoma that has been adequately treated or excised, squamous cell cancer of the skin, and cervical carcinoma in situ)
• History of:
• Serious infection (defined as requiring parenteral antibiotics or hospitalization) within 3 months prior to the baseline visit;
• Active tuberculosis or history of tuberculosis without documented curative treatment and/or positive tuberculin reaction to PPD (Purified Protein Derivative)
• For patients starting anti-TNF therapy, a positive TB screening test and no record of effective prophylaxis according to local expert recommendations
• Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Other:
• Observational study
RA patients on standard DMARD therapy

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Division of Rheumatology, University of Alberta Hospital	Edmonton	Alberta
Canada	The Arthritis Research Group	Newmarket	Ontario
Canada	Saskatoon Osteoporosis Centre	Saskatoon	Saskatchewan
Canada	University of Sherbrooke	Sherbrooke	Quebec
Canada	Memorial University	St. John's	Newfoundland and Labrador
Canada	Arthritis Center, University of Manitoba	Winnipeg	Manitoba
Denmark	Department of Rheumatology, Copenhagen University Hospital at Glostrup	Glostrup
France	Service de Rheumatologie-CHU Bordeaux Pellegrin	Bordeaux
France	Le Roux Liana, Centre d'Investigation Clinique	Brest
France	Centre des Consultations et imagerie de l'appareil locomoteur service de rheumatologie	Lille
France	Departement de rheumatologie, Hopital Lapeyronie	Montpellier
France	Rheumatologie B, Hopital Cochin	Paris
France	Infirmiere de Recherche Clinique, CHU de Toulouse, Centre de Rheumatologie, Hopital Purpan	Toulouse
Germany	Kerckhoff-Klinik, Department of Rheumatology and Clinical Immunology	Bad Nauheim
Germany	Department of Rheumatology/Clinical Immunology, Medizinische Klinik-Rheumatologie und Klinische Immunologie	Berlin
Germany	Universitatsklinikum der Friedrich-Schiller-Universitat Jena, Klinik für Innere Medizin III/Rheumatologie/Osteologie	Jena
Germany	Dr Spieler	Zerbst
Ireland	Department of Rheumatology, St. Vincents University Hospital	Dublin
Israel	Tel Aviv Sourasky Medical Centre	Tel Aviv
Italy	University of Ferrara	Ferrara
Italy	University of Milan	Milan
Italy	Day Hospital Reumatologia	Milano
Italy	University of Padova	Padova
Italy	Catholic University of the Sacred Heart	Rome
Italy	Department of Rheumatology, University of Verona	Verona
Netherlands	Academic Medical Centre/University of Amsterdam	Amsterdam
Netherlands	Amsterdam VU University Medical Centre	Amsterdam
Netherlands	Academic Medical Centre/University of Amsterdam and Atrium Medical Centre Heerlen	Heerlen
Netherlands	Afdeling Reumatologie, Leids Universitair Medisch Centrum	Leiden
Norway	Department of Rheumatology, Diakonhjemmet Hospital	Oslo
United States	Johns Hopkins Arthritis Center, Johns Hopkins University	Baltimore	Maryland
United States	Division of Rheumatology, Columbia University, College of Physicians and Surgeons	New York	New York
United States	Rheumatologist Hospital for Special Surgery	New York	New York
United States	Division of Allergy, Immunology and Rheumatology, University of Rochester	Rochester	New York
United States	Seattle Rheumatology Associates	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Canadian Research & Education in Arthritis	Abbott

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  France,  Germany,  Ireland,  Israel,  Italy,  Netherlands,  Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the independent predictive validity of several soluble biomarkers for predicting structural damage in Rheumatoid Arthritis (RA).		24 Months
Secondary	To establish which modifiable clinical and laboratory predictors used in routine practice individually and in combination, have the strongest and the most consistent association with change in radiographic damage in patients on standard RA therapy.		24 Months