Treatment strategies for Rheumatoid Arthritis (BeSt - BehandelStrategieën in Reumatoïde Artritis)

ISRCTN	ISRCTN32675862
DOI	https://doi.org/10.1186/ISRCTN32675862
Secondary identifying numbers	1

Submission date: 20/12/2005
Registration date: 20/12/2005
Last edited: 22/06/2010

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.F. Allaart
Scientific

Leiden University Medical Center
Department of Rheumatology
C1-39
P.O. Box 9600
Leiden
2300 RC
Netherlands

Phone	+31 (0)71 5263598
Email	c.f.allaart@lumc.nl

Study information

Study design	Randomised Controlled Trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title
Study acronym	BeSt
Study objectives	There is a clinically and statistically significant difference in functional ability and progression of radiological joint damage after two years of follow-up in patients with early Rheumatoid Arthritis (RA) who receive initial combination therapy, combination therapy after failure of optimal treatment with Methotrexate (MTX), or initial therapy with a Tumour Necrosis Factor (TNF)alpha-blocking agent, compared to those receiving combination therapy after intensive treatment with the most effective consecutive single Disease Modifying Anti-Rheumatic Drugs (DMARDs).
Ethics approval(s)	The medical ethics committee at each participating centre approved the study protocol, and all patients gave written informed consent before study inclusion.
Health condition(s) or problem(s) studied	Rheumatoid arthritis
Intervention	Treatment or RA with established anti-rheumatic medication according to four different, accepted strategies: Group one: sequential monotherapy Group two: step-up combination therapy Group three: initial combination therapy with tapered high-dose prednisone Group four: initial combination therapy with infliximab All medication steps are dictated by a strategy specific pharmacoprotocol. Treatment adjustments made on the basis of three monthly measurements of Disease Activity Score (DAS) (or on occurrence of side effects). All patients are treated aggressively, aiming at low disease activity, based on three monthly calculations of a DAS. In all four strategy groups the medication is increased or altered if the DAS is 2.4 or higher, or, if the DAS is less than 2.4 for at least six months, tapered to a single drug maintenance dose. A trained research nurse who remains blinded for the treatment that patients receive calculates the DAS.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Methotrexate, infliximab, prednisone
Primary outcome measure	After two years of follow-up: 1. Functional ability as measured by HAQ (collected by blinded research nurse) 2. Joint damage on X-rays of hands and feet (Sharp/van der Heijde method, random in time, by two independent physicians, X-rays masked for center and patient identity)
Secondary outcome measures	1. Side effects 2. Quality of life 3. Utilities 4. Costs
Overall study start date	01/03/2000
Completion date	01/08/2004

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Not Specified
Target number of participants	508
Key inclusion criteria	1. Patients (18 years or older) with rheumatoid arthritis (American College of Rheumatology [ACR] 1987 criteria) 2. Diagnosis since less than two years 3. Previously untreated with DMARDs 4. With active disease (at least 6/66 swollen and at least 6/68 painful joints, and either Erythrocyte Sedimentation Rate [ESR] 28 mm or more or Visual Analogue Scale [VAS] general well being (by patient) of 20 mm or more)
Key exclusion criteria	1. Previous therapy with DMARDs except for hydroxychloroquine 2. Pregnancy or wish to become pregnant during the study, or childbearing potential without adequate contraception 3. Concomitant treatment with another experimental drug 4. History or presence of malignancy within the last five years 5. Bone marrow hypoplasia 6. Elevated hepatic enzyme levels (Aspartate Aminotransferase [ASAT], Alanine Aminotransferase [ALAT] greater than three times normal value) 7. Serum creatinine level greater than 150 umol/l or estimated creatinine clearance of less than 75 ml/min 8. Diabetes mellitus 9. Alcohol or drug abuse
Date of first enrolment	01/03/2000
Date of final enrolment	01/08/2004

Locations

Countries of recruitment

Netherlands

Study participating centre

Leiden University Medical Center,

Leiden
2300 RC
Netherlands

Sponsor information

Leiden University Medical Centre (LUMC) (Netherlands)
University/education

Albinusdreef 2
P.O. Box 9600
Leiden
2300 RC
Netherlands

Website	http://www.lumc.nl/
"ROR"	https://ror.org/027bh9e22

Funders

Funder type

Industry

Centocor (Netherlands)

No information available

Schering-Plough (Netherlands)
Private sector organisation / For-profit companies (industry)

Location: United States of America

Dutch Health Care Insurance Board (CVZ, independent governement organisation) (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	Peer reviewed?	Patient-facing?
Results article	results	20/03/2007	Yes	No
Results article	results	01/09/2007	Yes	No
Results article	results	01/07/2010	Yes	No