Effects of addition of low-dose oral daily corticosteroids to the initial anti-rheumatic therapy on radiographic damage and disease activity in patients with early rheumatoid arthritis
| ISRCTN | ISRCTN20612367 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN20612367 |
| Secondary identifying numbers | N/A |
- Submission date
- 27/12/2013
- Registration date
- 04/02/2014
- Last edited
- 11/03/2015
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
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
Contact information
Scientific
Karolinska University Hospital Huddinge
Rheumatology Unit R92
Stockholm
14186
Sweden
Study information
| Study design | Comprehensive cohort study incorporating a randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | The patient information sheet was in Swedish only (not available in web format). All patients gave their informed consent. |
| 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 |
| Study objectives | 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(s) | 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 |
| Health condition(s) or problem(s) studied | 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 |
| Primary outcome measure | 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 study start date | 01/09/1995 |
| Completion date | 01/12/1999 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 80 Years |
| Sex | Both |
| Target number of participants | The planned Sample Size (>160 patients) was achieved. Sample Size: 250. |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/09/1995 |
| Date of final enrolment | 01/12/1999 |
Locations
Countries of recruitment
- Sweden
Study participating centre
14186
Sweden
Sponsor information
University/education
Department of Medicine
Karolinska University Hospital Huddinge M54
Stockholm
14186
Sweden
"ROR" |
https://ror.org/056d84691 |
|---|
Funders
Funder type
Research organisation
No information available
No information available
No information available
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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 | 01/11/2005 | Yes | No | |
| Results article | results | 01/11/2008 | Yes | No | |
| Results article | results | 01/04/2013 | Yes | No | |
| Results article | 10-year follow-up results | 07/04/2014 | Yes | No | |
| Results article | results | 30/07/2014 | Yes | No |
