Rheumatoid arthritis (RA) is a common chronic inflammatory disease that causes pain, stiffness, swelling and limited motion of joints. RA can affect any joint (most commonly the small joints in the hands and feet) and can develop at any age. RA is thought to be an autoimmune disease, which means that something triggers the immune system to make an immune reaction (this includes the production of antibodies) that may cause damage to joint tissues. Over time, damage to the joint, may lead to destruction of cartilage and bone. In some patients, the inflammation can affect other organs such as blood vessels, the eyes or lungs. If not adequately treated, the condition may lead to permanent damage to joints and disability, affecting quality of life.
Who can participate?
The purpose of this study is to determine whether rheumatoid arthritis (RA) can be prevented if therapy is given to individuals at high risk of developing the disease, as defined by the presence of autoantibodies in the blood, together with joint symptoms (pain but not joint swelling). In a controlled clinical trial setting, the feasibility, acceptability and effectiveness of a 12 month course of therapy with a drug called abatacept (already licensed for use in patients with established RA) will be investigated in subjects at high risk of developing RA. This drug has been chosen because it has beneficial effects in established RA, a good safety profile, and because of its beneficial effects on reducing harmful immune responses. At the same time we plan to investigate immune and inflammatory responses before, during and after therapy with abatacept in order to better understand the immune system at the very earliest detectable stages of disease.
What does the study involve?
The APIPPRA study aims to recruit 206 male or female subjects from hospitals across the UK and the Netherlands.
For entry into the study, the following criteria MUST be met:
- Male or female subjects, aged ≥ 18 years.
- Arthralgia, defined as non-traumatic joint pain (but no swelling) localised to synovial joints including, but not necessarily confined to, hands, wrists or feet.
- Positive for serum autoantibodies known to be associated with RA; these are known as rheumatoid factor and anti-CCP antibodies.
- Able and willing to give written informed consent and comply with the requirements of the study protocol.
What are the possible benefits and risks of participating?
The study is designed as a randomised, double blind, placebo-controlled clinical trial. This means that participants will be randomly allocated to receive weekly injections of either abatacept (the drug licensed for use in established RA) or dummy (placebo) treatment over a 12 month period. This provides the best chance of establishing whether differences observed between the two groups are due to the treatment.
Treatment Period (Year 1): The treatment will start at baseline (first) visit and participants will self-administer weekly injections for 12 months and will be seen in the outpatient clinic every 3 months. Blood and urine tests will be performed during these visits and some of the blood and urine will be used for routine monitoring of the effects of the study medication. Participants will also have an ultrasound scan of their joints at the first study visit (baseline visit) and at 6, 12, 18 and 24 months, which may be performed on the same day. In addition to the 3 monthly visits, there will be brief telephone consultations to check that study subjects are administering their weekly injections, and to ask if there have been any changes in their symptoms.
Follow up (Year 2): Once Participants have completed the 12 month course of treatment, they will be seen in the outpatient clinic every 3 months for similar assessments to those in year 1, to monitor the impact of the treatment phase. This follow up period is especially important because if at any time participants develop new joint pains or swelling they will be assessed promptly and treated appropriately, in a similar way that clinical staff would assess any new patient presenting with arthritis.
Where is the study run from?
We cannot predict the outcome of the study, but there is the possibility that there will be benefits to those subjects receiving the active drug, including reduction of joint symptoms and effects on the disease process that could delay or even prevent the onset of arthritis or RA. Another important benefit to participating is that you will be monitored very closely by the clinical research team. You will have a dedicated research nurse who you will be able to contact directly with any questions or concerns relating to your care or participation throughout the study. This means that should you develop rheumatoid arthritis at any point during the study you will be assessed and treated promptly.
Additionally, although not of direct benefit to you, your participation in this study will provide important new information about the feasibility and acceptability of approaches to preventing conditions such as RA, such as those adopted for the APIPPRA study.
Subjects receiving active treatment could experience some of the following side effects:
Throat or chest infections, headache, blood pressure increase, changes in liver function, diarrhoea, nausea, sore throat, fever, rashes, reduced white blood cell and fatigue and risk of injection site reactions in the skin.
In general these are mild, and previous clinical trials of abatacept have shown that the medication is well tolerated in patients with early as well as established RA. Nevertheless, for these reasons participants will be monitored closely through regular clinical assessments and blood testing so that any infections or side effects can be treated promptly.
How long is the study expected to run for?
The APIPPRA study has been set up by the Clinical Trials Group, Academic Department of Rheumatology, at King’s College London and Guy’s and St Thomas’ NHS Foundation Trust (who are also co-sponsors of the study) and will be run from up to 30 study sites across the UK and the Netherlands.
Who is funding the study?
Participants will be enrolled in the study for a period of 12 months of treatment with a further 12 months of follow up monitoring for the development of arthritis.
Who is the main contact?
The trial is funded by an Investigator Sponsored Research (ISR) grant from Bristol-Myers Squibb award to the Chief Investigator, Professor Andrew Cope.