Condition category
Musculoskeletal Diseases
Date applied
20/12/2005
Date assigned
20/12/2005
Last edited
22/06/2010
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr C.F. Allaart

ORCID ID

Contact details

Leiden University Medical Center
Department of Rheumatology
C1-39
P.O. Box 9600
Leiden
2300 RC
Netherlands
+31 (0)71 5263598
c.f.allaart@lumc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

1

Study information

Scientific title

Acronym

BeSt

Study hypothesis

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

The medical ethics committee at each participating centre approved the study protocol, and all patients gave written informed consent before study inclusion.

Study design

Randomised Controlled Trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

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

Phase

Not Specified

Drug names

Methotrexate, infliximab, prednisone

Primary outcome measures

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 trial start date

01/03/2000

Overall trial end date

01/08/2004

Reason abandoned

Eligibility

Participant 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)

Participant type

Patient

Age group

Adult

Gender

Not Specified

Target number of participants

508

Participant 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

Recruitment start date

01/03/2000

Recruitment end date

01/08/2004

Locations

Countries of recruitment

Netherlands

Trial participating centre

Leiden University Medical Center,
Leiden
2300 RC
Netherlands

Sponsor information

Organisation

Leiden University Medical Centre (LUMC) (Netherlands)

Sponsor details

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

Sponsor type

University/education

Website

http://www.lumc.nl/

Funders

Funder type

Industry

Funder name

Centocor (Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Schering-Plough (Netherlands)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Funder name

Dutch Health Care Insurance Board (CVZ, independent governement organisation) (Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17371885
2. 2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17405834
3. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20472597

Publication citations

  1. Results

    Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Peeters AJ, de Jonge-Bok JM, Mallée C, de Beus WM, de Sonnaville PB, Ewals JA, Breedveld FC, Dijkmans BA, Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial., Ann. Intern. Med., 2007, 146, 6, 406-415.

  2. Results

    Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, Kerstens PJ, Grillet BA, de Jager MH, Han KH, Speyer I, van der Lubbe PA, Seys PE, Breedveld FC, Dijkmans BA, Patient preferences for treatment: report from a randomised comparison of treatment strategies in early rheumatoid arthritis (BeSt trial)., Ann. Rheum. Dis., 2007, 66, 9, 1227-1232, doi: 10.1136/ard.2006.068296.

  3. Results

    Klarenbeek NB, van der Kooij SM, Huizinga TJ, Goekoop-Ruiterman YP, Hulsmans HM, van Krugten MV, Speyer I, de Vries-Bouwstra JK, Kerstens PJ, Huizinga TW, Dijkmans BA, Allaart CF, Blood pressure changes in patients with recent-onset rheumatoid arthritis treated with four different treatment strategies: a post hoc analysis from the BeSt trial., Ann. Rheum. Dis., 2010, 69, 7, 1342-1345, doi: 10.1136/ard.2009.124180.

Additional files

Editorial Notes