Clinical trial NCT01476956: Assess Structural Damage in Rheumatoid Arthritis Using Biomarkers and Radiography
Official title: Prospective Validation of Soluble Biomarkers as Predictors of Structural Damage in Rheumatoid Arthritis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rheumatoid Arthritis
Lead sponsor: CARE ARTHRITIS LTD.
Sponsor class: INDUSTRY
Collaborators: name: Abbott
First posted: 2011-11-22
Enrollment: 571
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: RA patients from rheumatologists' clinics

Brief 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.

Detailed 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.

Eligibility criteria: 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-TNFα 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-TNFα 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

Primary outcomes:
measure: To determine the independent predictive validity of several soluble biomarkers for predicting structural damage in Rheumatoid Arthritis (RA).
timeFrame: 24 Months
Secondary outcomes:
measure: 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.
timeFrame: 24 Months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Arthritis Center, Johns Hopkins University
state: Maryland
city: New York
country: United States
facility: Rheumatologist Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Division of Rheumatology, Columbia University, College of Physicians and Surgeons
state: New York
city: Rochester
country: United States
facility: Division of Allergy, Immunology and Rheumatology, University of Rochester
state: New York
city: Seattle
country: United States
facility: Seattle Rheumatology Associates
state: Washington
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Division of Rheumatology, University of Alberta Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: Arthritis Center, University of Manitoba
state: Manitoba
city: St. John's
country: Canada
facility: Memorial University
state: Newfoundland and Labrador
city: Newmarket
country: Canada
facility: The Arthritis Research Group
state: Ontario
city: Sherbrooke
country: Canada
facility: University of Sherbrooke
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Osteoporosis Centre
state: Saskatchewan
city: Glostrup
country: Denmark
facility: Department of Rheumatology, Copenhagen University Hospital at Glostrup
city: Bordeaux
country: France
facility: Service de Rheumatologie-CHU Bordeaux Pellegrin
city: Brest
country: France
facility: Le Roux Liana, Centre d'Investigation Clinique
city: Lille
country: France
facility: Centre des Consultations et imagerie de l'appareil locomoteur service de rheumatologie
city: Montpellier
country: France
facility: Departement de rheumatologie, Hopital Lapeyronie
city: Paris
country: France
facility: Rheumatologie B, Hopital Cochin
city: Toulouse
country: France
facility: Infirmiere de Recherche Clinique, CHU de Toulouse, Centre de Rheumatologie, Hopital Purpan
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik, Department of Rheumatology and Clinical Immunology
city: Berlin
country: Germany
facility: Department of Rheumatology/Clinical Immunology, Medizinische Klinik-Rheumatologie und Klinische Immunologie
city: Jena
country: Germany
facility: Universitatsklinikum der Friedrich-Schiller-Universitat Jena, Klinik für Innere Medizin III/Rheumatologie/Osteologie
city: Zerbst
country: Germany
facility: Dr Spieler
city: Dublin
country: Ireland
facility: Department of Rheumatology, St. Vincents University Hospital
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Centre
city: Ferrara
country: Italy
facility: University of Ferrara
city: Milano
country: Italy
facility: Day Hospital Reumatologia
city: Milan
country: Italy
facility: University of Milan
city: Padova
country: Italy
facility: University of Padova
city: Rome
country: Italy
facility: Catholic University of the Sacred Heart
city: Verona
country: Italy
facility: Department of Rheumatology, University of Verona
city: Amsterdam
country: Netherlands
facility: Amsterdam VU University Medical Centre
city: Amsterdam
country: Netherlands
facility: Academic Medical Centre/University of Amsterdam
city: Heerlen
country: Netherlands
facility: Academic Medical Centre/University of Amsterdam and Atrium Medical Centre Heerlen
city: Leiden
country: Netherlands
facility: Afdeling Reumatologie, Leids Universitair Medisch Centrum
city: Oslo
country: Norway
facility: Department of Rheumatology, Diakonhjemmet Hospital
Study officials:
affiliation: CaRE Arthritis
name: Walter P. Maksymowych, MD
role: STUDY_DIRECTOR
References:
citation: Sepriano A, Ramiro S, FitzGerald O, Ostergaard M, Homik J, van der Heijde D, Elkayam O, Thorne JC, Larche MJ, Ferraccioli G, Backhaus M, Burmester GR, Boire G, Combe B, Schaeverbeke T, Saraux A, Dougados M, Rossini M, Govoni M, Sinigaglia L, Cantagrel A, Barnabe C, Bingham CO 3rd, Tak PP, van Schaardenburg D, Hammer HB, Paschke J, Dadashova R, Hutchings E, Landewe R, Maksymowych WP. Adherence to Treat-to-target Management in Rheumatoid Arthritis and Associated Factors: Data from the International RA BIODAM Cohort. J Rheumatol. 2020 Jun 1;47(6):809-819. doi: 10.3899/jrheum.190303. Epub 2019 Sep 15.
citation: Maksymowych WP, FitzGerald O, Ostergaard M, Homik J, van der Heijde D, Lambert RG, Elkayam O, Ramiro S, Thorne JC, Larche MJ, Ferraccioli G, Backhaus M, Burmester GR, Boire G, Combe B, Schaeverbeke T, Saraux A, Dougados M, Rossini M, Govoni M, Sinigaglia L, Cantagrel A, Barnabe C, Bingham CO 3rd, Tak PP, van Schaardenburg D, Hammer HB, Paschke J, Dadashova R, Hutchings E, Sepriano A, Landewe R. Outcomes and Findings of the International Rheumatoid Arthritis (RA) BIODAM Cohort for Validation of Soluble Biomarkers in RA. J Rheumatol. 2020 Jun 1;47(6):796-808. doi: 10.3899/jrheum.190302. Epub 2019 Sep 1.