Plain English Summary
Background and study aims
Behçet’s disease (BD) is a rate and poorly understood condition that causes inflammation (swelling) throughout the body. The inflammation associate with BD can cause a wide range of symptoms, including genital and mouth ulcers, eye problems (which can lead to blindness), skin rashes and inflammation of the blood vessels, which increases a person’s risk of developing blood clots and stroke. The exact cause of BD is unknown however many believe it is an autoimmune disorder (in which the body’s immune system mistakenly attacks the body’s own, healthy tissue). Traditional treatments include corticosteroids (anti-inflammatory medicine) and immunosuppressant drugs (medications that reduce the activity of the immune system), but they can have unpleasant side effects. Biologic therapies are a newer type of medication, which target the biological processes involved in the process of inflammation more selectively. Recently, the biologic drugs infliximab and interferon alpha (aIFN) have been used successfully in treating BD however they are expensive (£16,000/year and £4,000/year, respectively), not always effective and there have been very few studies looking at their effectiveness. The Department of Health has recently commissioned three national Centres of Excellence for BD in London, Birmingham and Liverpool, with the remit to deliver care for the approximate 500 UK patients currently with this condition. The aim of this study is to compare the effectiveness of infliximab with aIFN at treating patients with BD.
Who can participate?
Adults with BD who are suitable to receive biological therapy.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group are treated with infliximab. This is given through a drip (intravenous infusion) at the standard dose of 5mg/kg at the start of the study, week 2, week 6 and then every 8 weeks until the end of the study. Those in the second group are treated with aIRN. This is given as an injection under the skin (subcutaneous injection) starting at a dose of 3 million units one a day for 3 days, then 6 million units (for men who weight more than 80kg) or 4.5 million units (for women or men weighing less than 80kg) every day. This dose can be reduced down every 2-4 weeks if necessary to 3 million units twice a week over the course of the study. After 3 and 6 months of treatment, participants in both groups are assessed in order to find out if there has been any improvement to their condition.
What are the possible benefits and risks of participating?
Not provided at time of registration.
Where is the study run from?
University of Liverpool (UK)
When is the study starting and how long is it expected to run for?
April 2016 to December 2019
Who is funding the study?
Medical Research Council (UK)
Who is the main contact?
Miss Elizabeth Blennerhassett
Trial website
Additional identifiers
EudraCT number
2014-005390-36
ClinicalTrials.gov number
Protocol/serial number
20233
Study information
Scientific title
BIO BEHÇET’S: Optimal utilisation of biologic drugs in Behçet’s Disease: a randomised controlled trial of infliximab vs alpha interferon, with genotyping and metabolomic profiling, towards a stratified medicines approach to treatment
Acronym
BIO BEHÇET’S
Study hypothesis
The aim of the study is to create the evidence base to underpin clinically effective prescribing of the biologic drugs infliximab and alpha interferon for Behçet’s Disease.
The objectives of the study are to:
1. Undertake a randomised controlled trial to compare IFX versus aIFN in patients with BD who are unresponsive to standard oral therapy
2. Examine whether IFNL3 and IFNL4 SNPs can predict response to aIFN and/or IFX in BD
3. Examine the potential for urine metabolomics to act as biomarker for drug response to IFX and/or aIFN in BD
Ethics approval
North West - Liverpool Central Research Ethics Committee, 17/02/2015, 15/NW/0008
Study design
Randomised two-arm parallel open-label design
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Musculoskeletal; Subtopic: Musculoskeletal (all Subtopics); Disease: Musculoskeletal
Intervention
Participants are randomly allocated to one of two groups.
Group 1: Participants will receive infliximab at a standard dose of 5mg/kg at week 0, week 2 and week 6 as loading then every 8 weeks for the length of the trial.
Group 2: Interferon alpha (Roferon) subcutaneous injection in tapering dose starting at 3 million units once daily for three days, then 6** million units once daily (male with body weight more than 80 kg) or 4.5 million units once daily (female, or male with weight less than 80 kg). Dose tapered down every 2-4 weeks according to defined clinical criteria to 3 million units twice a week, over the period of the trial.
** The six million units dose will only be administered to males of over 80 kg with major organ threatening disease (e.g., severe eye involvement). Males of less than 80kg or females will start with 4.5 million.
Intervention type
Other
Phase
Drug names
Primary outcome measures
Disease severity is measured using the Behcet's disease activity index (BDAI) after 3 months of treatment.
Secondary outcome measures
1. Disease severity is measured using the Behcet's disease activity index (BDAI) after six months of treatment,
2. Significant improvement in organ involvement within the primary organ system that resulted in the decision to start a biologic agent and other organ systems assessed by:
2.1. Ocular: reduction in vitreous haze using the SUN consensus group grading scale and visual acuity change from baseline
2.2. Oral ulcer activity: change in ulcer severity score (USS)
2.3. Change in number of genital ulcers
2.4. Musculoskeletal: Likert pain score
3. Adverse events in each group
4. Reduction in dose of prednisolone (or equivalent glucocorticoid) at three months: a clinically meaningful reduction is considered to be 50% of baseline or dose of <15mg/day prednisolone
5. Reduction in dose of prednisolone (or equivalent glucocorticoid) at six months: a clinically meaningful reduction is considered to be 50% of baseline or dose of <7.5mg/day prednisolone
6. Quality of life is measured using EQ-5D and BD-QoL at baseline, 3 and 6 months
7. Disease activity is measured using the Physician’s Global Assessment of disease activity (a 7 point Likert Scale completed as part of (but assessed independently of) the BDAI) at 3 and 6 months
Overall trial start date
01/04/2016
Overall trial end date
31/12/2019
Reason abandoned
Eligibility
Participant inclusion criteria
1. Diagnosed to have BD by International Study Group (ISG) criteria or International Criteria for BD (ICBD)
2. Have refractory disease as defined by the UK Centres of Excellence criteria (failure to respond to steroid and/or immunosuppressive therapy with significant or major organthreatening disease) and therefore qualify for biologic therapy with either IFX or aIFN
3. Able to give informed consent
4. Have not previously received a biologic agent
5. Aged over 18 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 100; UK Sample Size: 100
Participant exclusion criteria
1. Have a contraindication to either IFX or aIFN (eg active infection, severe liver disease, neutropenia, previous malignancy)
2. Are likely to not comply: for example cannot attend assessments because of excessive travel requirements
3. Are already, or likely to become, pregnant during the study
4. Express a strong preference for one of the two potential therapies
5. Have heart disease or severe heart failure
6. Have been diagnosed with Multiple sclerosis
7. Have evidence of infection with HIV
Recruitment start date
01/04/2016
Recruitment end date
31/12/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University of Liverpool
Department of Health Services Research
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
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