Extrait

Background and study aims Rheumatoid arthritis is a long-term condition that causes pain, swelling and stiffness in the joints. There are several treatment options for rheumatoid arthritis, such as anti-TNFα treatment, which blocks the action of the signalling protein TNFα and can reduce inflammation, but patients show different levels of response to these treatments. This study focuses on uncovering reasons for this observed difference in participants treated with anti-TNFα treatment and aims to reveal the key pathways that can be targeted to ensure the best clinical outcomes. This research may be able to identify disease characteristics that determine which future patients may be more likely to respond to anti-TNFα treatment, or those who may require a different treatment option to achieve a clinical response. IL-17 is a signalling protein in the body’s immune system. The main aim of this study is to examine the relationship between the levels of IL-17 in the blood and joints and clinical response or non-response to anti-TNFα treatment. Who can participate? Patients aged 18 to 65 with active rheumatoid arthritis who qualify for anti-TNFα treatment. What does the study involve? Participants will be asked to provide blood and urine samples. Pieces of genetic information called RNA will be extracted from the blood samples (and biopsy material if you are part of the biopsy sub-study) provided by participants. This material will be analysed to reveal information about what genes are ‘active’ in the joint environment during the anti-TNFα treatment. This information can tell us what proteins might be involved in the inflammation of affected joints and might also be able to predict what type of response you will experience to different treatments. The analysis of research samples from this study will provide new information on the mechanisms for response/non-response. A number of participants that have consented to the main study will be invited to take part in the optional biopsy sub-study. This will involve taking a biopsy of one of the affected joints via an ultrasound-guided procedure. The procedure is minimally invasive and has good safety and tolerability with participants. The procedure is performed under local anaesthetic and removes tiny pieces of inflamed tissue from the lining of the joint using a needle under the guidance of an ultrasound scanner. This sub-study will collect tissue from affected joints to help answer the research questions in this study Participants are also invited to take part in the optional DNA genetic sampling and are asked to contribute DNA samples for this study. The purpose of this optional part of the research study is to help understand how anti-TNFα treatments work and how they may cause side effects, to further understand rheumatoid arthritis, and to understand why some people respond to anti-TNFα treatments while others do not. Genetic (genotyping) testing refers to the patient sample being used for genetic research. This is the study of DNA and how it determines our traits. DNA research can also explain why some people respond well to their medications and others do not and can also provide reasons as to why some people develop some diseases and others do not. Samples from participants that have consented to the optional DNA genetic sampling will also be used for a type of genetic research called epigenetics. This is the study of chemical modifications of DNA that occur over time, without a change in DNA sequence. These modifications control the way cells produce proteins and respond to the environment. Epigenetics research is not a test to diagnose a person for a genetic disease or to determine whether a person may have a risk of developing a genetic disease. It is only used to understand prevailing disease and how drugs may work in different groups of people. In epigenetic testing, DNA samples from participants will be analysed to determine how this may influence response to anti-TNFα treatments. What are the possible benefits and risks of participating? The medication that is used throughout this clinical study is part of normal practice in the management of rheumatoid arthritis, and so there will be no additional advantage to taking part in this study. The findings may help make the best treatment choices for people with rheumatoid arthritis. This study poses no greater risk than would be expected in routine clinical care. The biopsies are not considered routine care and thus the main risks to participants would be associated with this procedure. Participation in this sub-study will be optional. The procedure has excellent safety and tolerability and is carried out under local anaesthetic in a sterile setting by highly experienced doctors. However, like all procedures of this kind, it does carry some small risks, including infection of the joint or skin, bleeding, pain and rarely nerve or tendon damage (less than 1:10,000 risk). Where is the study run from? Queen Mary University of London (UK). When is the study starting and how long is it expected to run for? From March 2015 to August 2016. Who is funding the study? Janssen Pharmaceuticals Inc. (USA) and NIHR Translational Research Partnerships (UK). Who is the main contact? Martha Bajwa Joseph

Critère d'inclusion

• Topic: Musculoskeletal disorders; Subtopic: Musculoskeletal (all Subtopics); Disease: Musculoskeletal

Liens

• ictrp
• isrctn