Condition category
Musculoskeletal Diseases
Date applied
27/12/2013
Date assigned
04/02/2014
Last edited
11/03/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Rheumatoid arthritis (RA) is an autoimmune disorder when the body tissue is mistakenly attacked by its own immune system. This causes inflammation of the joints, with destruction of bone around the involved joints. Experts suggest that preventing early joint damage can have huge long-term benefits. Early, aggressive treatment is the key to slowing or stopping RA progression and joint destruction. Corticosteroids (prednisolone) decrease inflammation and reduce the activity of the immune system. Added to other anti-rheumatic medication, low doses of corticosteroids may provide significant relief from pain and stiffness for people with rheumatoid arthritis. Our aim was to find out if addition of low-dose corticosteroids to the usual treatment soon after diagnosing RA may help to stop joint damage, improve inflammatory-related signs and symptoms of RA and improve disease outcomes in the long run. Further, we wanted to study if these effects could be achieved without serious toxicity issues.

Who can participate?
Adult men and women aged 18-80 years with newly diagnosed active RA can participate in this study.

What does the study involve?
Eligible patients were allocated at random to take either prednisolone (corticosteroids) daily or no prednisolone over a period of two years. Other anti-rheumatic drugs were selected by the treating specialist according to current recommendations. Participants were seen at the beginning of the study and at 3, 6, 12, 18, and 24 months for follow up. Disease activity was measured and questionnaires about physical function were completed. X-ray of the hands and feet were obtained at study entry and after 1 and 2 years. Participants were also invited to give blood to a biobank for studies of prediction of RA disease course and complications.

What are the possible benefits and risks of participating?
Taking corticosteroids may reduce the rate of worsening of the disease in the affected joints. This study may help in deciding the best treatment for future patients with early RA. We believe that this study may also help to tailor the treatment to the individual patient's characteristics and needs. Possible side effects as high blood pressure, increased lipid content in blood and heart-related complications were looked for and registered if they occurred at all.

Where is the study run from?
This study took place in six rheumatologic clinics (Helsingborg, Kristianstad, Mölndahl, Spenshult, Kalmar, Huddinge) in southern Sweden.

When is the study starting and how long is it expected to run for?
Participants were recruited between September 1995 and December 1999. However, the study follow-up was extended beyond two years of follow up, as we wanted to look at participants' health over many years to assist future studies about the course, treatments and complications of RA disease.

Who is funding the study?
1. The Swedish Rheumatism Association (Sweden)
2. King Gustav V 80-years foundation (Sweden)
3. The Ugglas Foundation (Sweden)
4. The Börje Dahlins Foundation (Sweden)
5. The Gorthon Foundation in Helsingborg (Sweden)
6. Foundation for assistance to disabled people in Skåne (Stiftelsen för Rörelsehindrade i Skåne) (Sweden)

Who is the main contact?
Dr Sofia Ajeganova
sofia.ajeganova@karolinska.se

Trial website

Contact information

Type

Scientific

Primary contact

Dr Sofia Ajeganova

ORCID ID

Contact details

Karolinska University Hospital Huddinge
Rheumatology Unit R92
Stockholm
14186
Sweden

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Effects of addition of low-dose oral daily prednisolone to the initial disease-modifying anti-rheumatic drugs (DMARD) therapy on progression of radiographic damage and disease activity in patients with early rheumatoid arthritis, as well as effects on adverse outcomes and toxicity

Acronym

Study hypothesis

To evaluate if low-dose prednisolone, 7.5 mg daily, added to DMARD therapy over the first two years after diagnosis of RA was able to reduce the progression of joint destruction and provide sustained reduction of disease activity with an acceptable level of toxicity/adverse outcome, including effect on bone mineral density.

Ethics approval

1. Lund University, ref: LU 154-95
2. Gothenburg University, ref: Gbg M45-95
3. Karolinska Institutet (Karolinska Institute), ref: KI 153-95
4. Linköping University, ref: Li 123-95

Study design

Comprehensive cohort study incorporating a randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

The patient information sheet was in Swedish only (not available in web format). All patients gave their informed consent.

Condition

Rheumatoid arthritis

Intervention

The patients were recruited from the 6 centres involved in the BARFOT (Better Anti-Rheumatic FarmacOTherapy) Study Group in southern Sweden. The randomization was done as block randomization for each centre according to a central randomization with stratification for sex. At start of the first DMARD the participants had been randomised to either 7.5 mg prednisoone daily, orally (P group), or no prednisolone (NoP group) for the first 2 years. The choice of DMARD was left to the treating physicians, who followed the recommended treatment strategy in Sweden at the time of the study. All patients were given 1000 mg calcium per day.

Study entry: registration only

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

The difference in changes in radiographic damage scores after 2 years
Timepoint(s): Pre- and post-intervention. Clinical assessment at the start of the study and at 3, 6, 12, 18, and 24 months. Radiographic evaluation at baseline and after 1 and 2 years

Secondary outcome measures

1. Remission rates and differences in disease activity and function
2. Adverse events

Overall trial start date

01/09/1995

Overall trial end date

01/12/1999

Reason abandoned

Eligibility

Participant inclusion criteria

1. Diagnosis of RA according to the 1987 revised criteria of the American College of Rheumatology (ACR)
2. Age 18-80 years
3. Disease duration of ≤ 1 year
4. Active disease defined as a Disease Activity Score in 28 joints (DAS28) of >3.0
5. Started by the treating rheumatologist on the first DMARD

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

The planned Sample Size (>160 patients) was achieved. Sample Size: 250.

Participant exclusion criteria

1. Earlier treatment with glucocorticoids for RA or other diseases
2. Previous treatment with DMARDs
3. Contraindication for glucocorticoid therapy
4. Previous fragility fractures
5. Patients aged < 65 years with a T-score lower than -2.5 on bone densitometry; and patients aged ≥ 65 years with a Z-score of less than -1

Recruitment start date

01/09/1995

Recruitment end date

01/12/1999

Locations

Countries of recruitment

Sweden

Trial participating centre

Karolinska University Hospital Huddinge
Stockholm
14186
Sweden

Sponsor information

Organisation

Karolinska Institute (Karolinska Institutet) (Sweden)

Sponsor details

Department of Medicine
Karolinska University Hospital Huddinge M54
Stockholm
14186
Sweden

Sponsor type

University/education

Website

Funders

Funder type

Research organisation

Funder name

The Swedish Rheumatism Association (Sweden)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

King Gustav V 80-years foundation (Sweden)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Ugglas Foundation (Sweden)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Börje Dahlins Foundation (Sweden)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

The Gorthon Foundation in Helsingborg (Sweden)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Foundation for assistance to disabled people in Skåne (Stiftelsen för Rörelsehindrade i Skåne) (Sweden)

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

2005 results in: http://www.ncbi.nlm.nih.gov/pubmed/16255010
2008 results in: http://www.ncbi.nlm.nih.gov/pubmed/18986531
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23275387
2014 10-year follow-up results in: http://www.ncbi.nlm.nih.gov/pubmed/24710131
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25079933

Publication citations

  1. Results

    Svensson B, Boonen A, Albertsson K, van der Heijde D, Keller C, Hafström I, Low-dose prednisolone in addition to the initial disease-modifying antirheumatic drug in patients with early active rheumatoid arthritis reduces joint destruction and increases the remission rate: a two-year randomized trial., Arthritis Rheum., 2005, 52, 11, 3360-3370, doi: 10.1002/art.21298.

  2. Results

    Engvall IL, Svensson B, Tengstrand B, Brismar K, Hafström I, , Impact of low-dose prednisolone on bone synthesis and resorption in early rheumatoid arthritis: experiences from a two-year randomized study., Arthritis Res. Ther., 2008, 10, 6, R128, doi: 10.1186/ar2542.

  3. Results

    Engvall IL, Svensson B, Boonen A, van der Heijde D, Lerner UH, Hafström I, , Low-dose prednisolone in early rheumatoid arthritis inhibits collagen type I degradation by matrix metalloproteinases as assessed by serum 1CTP--a possible mechanism for specific inhibition of radiological destruction., Rheumatology (Oxford), 2013, 52, 4, 733-742, doi: 10.1093/rheumatology/kes369.

  4. Ajeganova S, Svensson B, Hafström I, , Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outcome and survival: 10-year follow-up of a 2-year randomised trial., BMJ Open, 2014, 4, 4, e004259, doi: 10.1136/bmjopen-2013-004259.

  5. Results

    Hafström I, Engvall IL, Rönnelid J, Boonen A, van der Heijde D, Svensson B; BARFOT study group, Rheumatoid factor and anti-CCP do not predict progressive joint damage in patients with early rheumatoid arthritis treated with prednisolone: a randomised study, BMJ Open, 2014 , 4, 7, e005246, doi: 10.1136/bmjopen-2014-005246.

Additional files

Editorial Notes