Identification of predictive factors in synovial samples for the clinical response to tumour necrosis factor-alpha blockade in rheumatoid arthritis

ISRCTN	ISRCTN36847425
DOI	https://doi.org/10.1186/ISRCTN36847425
Secondary identifying numbers	N/A

Submission date: 01/02/2007
Registration date: 01/02/2007
Last edited: 01/08/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr C A Wijbrandts
Scientific

Academic Medical Center (AMC)
Department of Medicine
Division of Clinical Immunology and Rheumatology, F4-218
P.O. Box 22660
Amsterdam
1100 DD
Netherlands

Phone	+31 (0)20 566 2171
Email	c.a.wijbrandts@amc.uva.nl

Study information

Study design	Multicentre phase IV prospective study
Primary study design	Interventional
Secondary study design	Multi-centre
Study setting(s)	Not specified
Study type	Treatment
Scientific title
Study objectives	Can predictors of reponse to anti-Tumour Necrosis Factor (TNF) therapy be identified by immunohistochemical analysis of synovial tissue obtained before initiation of treatment?
Ethics approval(s)	Approval received from the Medical ethical committee of the Academic Medical Center/University of Amsterdam on the 14th February 2001 (ref: MEC 01/003).
Health condition(s) or problem(s) studied	Rheumatoid arthritis
Intervention	Infliximab therapy (3 mg/kg intravenous [i.v.]) at week zero, two, six, 14 and every eight weeks. Clinical efficacy assessments are performed at baseline and subsequently every four weeks up to week 24. Serum samples are drawn on these visits. At baseline synovial biopsies are obtained from a maximally inflamed joint.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase IV
Drug / device / biological / vaccine name(s)	Infliximab
Primary outcome measure	1. Primary immunohistological outcome: TNF-alpha expression in synovial tissue as shown by immunohistochemistry and quantified by digital image analysis 2. Primary clinical outcome: clinical response at week 16 assessed using the DAS 28
Secondary outcome measures	Secondary immunohistological outcome: analysis of the synovial cell infiltrate, and cytokines other than TNFalpha.
Overall study start date	01/04/2001
Completion date	01/05/2004

Eligibility

Participant type(s)	Patient
Age group	Not Specified
Sex	Both
Target number of participants	143
Key inclusion criteria	1. Men/women suffering from rheumatoid arthritis, based on the American Rheumatism Association (ARA) 1987 criteria, who failed at least one Disease Modifying Anti-Rheumatic Drug (DMARD) including methotrexate, will be included in the study 2. Patients in ARA functional classes I, II, and III may be included 3. In addition the patients must fulfill the following criteria at baseline: a. Disease Activity Score (DAS 28) more than 3.2 b. patients global evaluation of his/her rheumatoid condition assessed as fair, poor or very poor and investigators global evaluation of patients rheumatoid condition assessed as fair, poor or very poor c. more than 18 years of age and less than or equal to 85 years d. use concurrent methotrexate treatment (5 - 30 mg/week; stable since at least 28 days before initiation) during the study. Subjects may be taking nonsteroidal anti-inflammatory drugs, provided the dose and frequency have been stable for at least 28 days. Subjects may be receiving prednisone therapy of less than or equal to 10 mg/day provided that the dosage has been stable for at least two months prior to entry
Key exclusion criteria	1. Pregnancy 2. Breastfeeding 3. A history of or acute inflammatory joint disease of different origin e.g. mixed connective tissue disease, seronegative spondylarthropathy, psoriatic arthritis, Reiter's syndrome, systemic lupus erythematosus or any arthritis with onset prior to age 16 years 4. Acute major trauma 5. Previous therapy at any time with: TNF-alpha directed monoclonal antibodies or p75 TNF receptor fusion protein 6. Therapy within the previous 60 days with: a. any experimental drug b. alkylating agents, e.g. cyclophosphamide, chlorambucil c. antimetabolites d. monoclonal antibodies e. growth factors f. other cytokines 7. Therapy within the previous 28 days with: a. parenteral or intra-articular corticoid injections b. oral corticosteroid therapy exceeding a prednisone equivalent of 10 mg daily c. present use of DMARDs other than methotrexate 8. A history of hypersensitivity to the study medication or to drugs with similar chemical structure 9. Fever (orally measured as more than 38°C), chronic infections or infections requiring anti-microbial therapy 10. Known positive reaction to hepatitis B surface antigen 11. Other active medical conditions such as inflammatory bowel disease, bleeding diathesis, or severe unstable diabetes mellitus 12. Manifest cardiac failure (stage III or IV according to New York Heart Association [NYHA] classification) 13. Progressive fatal disease/terminal illness 14. Impaired coagulation 15. A congenital or acquired (known Human Immunodeficiency Virus [HIV]-positive status) immunodeficiency, a history of cancer or lymphoproliferative disease or treatment with total lymphoid irradiation (the known HIV-positive status may be defined either by a positive blood test or clinical diagnosis), or a haematopoietic disease 16. A white cell count less than 3.5 x 10^9/l 17. Platelet count less than 100 x 10^9/l 18. Haemoglobin of less than 5.3 mmol/l 19. Body weight of less than 45 kg 20. History of drug or alcohol abuse 21. Any concomitant medical condition which would, in the investigators opinion, compromise the patients ability to tolerate, absorb, metabolise or excrete the study medication 22. Inability to give informed consent 23. Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude
Date of first enrolment	01/04/2001
Date of final enrolment	01/05/2004

Locations

Countries of recruitment

Netherlands

Study participating centre

Academic Medical Center (AMC)

Amsterdam
1100 DD
Netherlands

Sponsor information

Academic Medical Centre (AMC) (The Netherlands)
Hospital/treatment centre

Division of Clinical Immunology and Rheumatology
P.O. Box 22660
Amsterdam
1100 DD
Netherlands

Website	http://www.amc.uva.nl/
"ROR"	https://ror.org/03t4gr691

Funders

Funder type

Research organisation

Dutch Arthritis Association (Reumafonds) (The Netherlands)

No information available

The Netherlands Organisation for Health Research and Development (ZonMw) (The Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/02/2011		Yes	No
Results article	exploratory study results	01/08/2011		Yes	No