R4-RA
Research type
Research Study
Full title
A Randomised, open labelled study in anti-TNFa inadequate responders to investigate the mechanisms for Response - Resistance to Rituximab versus Tocilizumab in RA (R4-RA)
IRAS ID
109361
Contact name
Costantino Pitzalis
Contact email
Sponsor organisation
Joint Research & Development Office (QMUL)
Eudract number
2012-002535-28
ISRCTN Number
00000000
Clinicaltrials.gov Identifier
00000000
Research summary
Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis and the diagnosis can have devastating consequences for those affected both medically, with severe joint pain, fatigue and a shortened life span, and socially with a diagnosis frequently resulting in unemployment, depression and social isolation. Although new types of treatment termed ??biological therapies? have revolutionized the outlook for patients with RA, approximately only 30% of patients respond completely to these treatments, with a further 30% responding partially and 40% having no response. At present guidance from the UK government body NIHCE (National Institute for Health and Clinical Excellence) states that all RA patients should be treated initially with a type of biologic drug called tumour necrosis factor inhibitors (TNFi) and when/if patients fail on these drugs either due to lack of effect or side effects they should be switched over to a different biologic medication called rituximab. Whether rituximab is the correct choice of drug at this stage is presently unknown, indeed there are a number of different biologic drugs, all licensed to treat RA, which could be used at this stage instead of rituximab, including a medication called tocilizumab. Again neither rituximab nor tocilizumab work for all patients who have failed treatment with TNFi and at present it is impossible to predict which patients will respond to which drug. Such a situation is very frustrating for both clinicians and patients as cycling through ineffective drugs can leave patients with months or years of suffering, biologic therapies can have serious side effects and furthermore they are very expensive treatments, costing upwards of approximately œ8,000 per year. Preliminary evidence suggests that examining a sample of the joint lining prior to starting treatment may help us decide which treatment is best for patients, but this evidence needs to be examined in a larger number of patients in a clinical trial setting. Thus the primary aim of this study is to examine in RA patients who have failed treatment with TNFis whether examination of specific markers with the joint lining can help guide clinicians to chose the most effective medication for patients. We are aiming to recruit all patients with RA over the age of 18 who have already failed treatment with TNFis who continue to have active arthritis. Patients will initially have a minor procedure to remove tiny pieces of joint lining (synovium) from one of joints that is clinically affected with arthritis, this is called an ultrasound guided synovial biopsy. Patients will be awake during the procedure as anaesthetic is only required to the skin and tissues immediately beneath it, the procedure takes around 20 minutes to perform and patients will be allowed home immediately following it. In addition to standard screening and safety blood tests an extra 3-4 teaspoons of blood with be taken at the initial study visit and at each monthly monitoring visit. The synovium will be examined and the results of this be used to randomize patients to treatment with either rituximab or tocilizumab. Patients will then be followed on a monthly basis to see if they are responding to treatment. if not responding patients will be given the opportunity to switch to the alternative therapy. Possible benefits of enrolling in the clinical trial are that patients may be randomized to receive treatment with tocilizumab earlier than in standard clinical practice in the UK, which maybe a more effective treatment for RA than rituximab. Possible risks of participating are the very small risk of complications (<1%) such as infections or post procedure joint pain following the synovial biopsy. There are also risks associated with receiving either rituximab or tocilizumab but as both are used within their licensed indications these are not above the risks if patients were to receive the treatment as part of standard care. The main side effects of either treatment is an increased risk of infections, such as chest infections, and also the possibility of reactions whilst receiving the medications.
REC name
Wales REC 3
REC reference
12/WA/0307
Date of REC Opinion
21 Nov 2012
REC opinion
Further Information Favourable Opinion