RecruitingPhase IVInterventional

Are RNA signatures (biomarkers) in the tissue which surrounds the joints (synovial tissue) from patients with rheumatoid arthritis predictive of response to drug treatments?

Rheumatoid arthritis causes painful, swollen joints. Advanced treatments called biologics can be very effective, but around 40% of patients do not get enough relief from the first one they try. Finding the right drug often involves months of trial and error. This clinical trial, led by Queen Mary University of London, tests whether a personalised approach works better. Doctors want to find out if biological clues (called RNA markers) in the joint lining can predict which medicine will work best for each individual. Participants will have a quick, ultrasound-guided joint biopsy and will be given one of two approved arthritis medicines: sarilumab or etanercept. Half will receive the drug matched to their tissue markers, while the other half will have their treatment chosen at random. The goal is to help future patients find the right treatment much faster.

At a glance

Status

Recruiting

Phase

Phase IV

Sponsor

Queen Mary University of London

Enrolment target

240

Start

20 Feb 2023

Estimated completion

01 Jan 2028

Rheumatoid arthritis

What is this study about?

Rheumatoid arthritis is a long-term condition where the immune system mistakenly attacks the lining of the joints, causing persistent pain, swelling, and stiffness. While standard tablet medicines work for many, others need stronger treatments known as biological therapies. However, everyone's body is different, and nearly 4 in 10 patients do not find relief with the first biologic drug they are prescribed. Today, doctors have no reliable way to know in advance which drug will work best for which person.

This study, called 3TR-Precis-The-RA, aims to move away from this guessing game. Researchers are studying whether taking a tiny piece of tissue from an inflamed joint (a biopsy) can reveal biological signposts called RNA markers. By analysing these markers, doctors hope to predict accurately whether an individual will respond better to a drug called sarilumab or one called etanercept.

Finding the right treatment quickly is vital. It prevents long delays in getting joint pain under control and avoids exposing people to medicines that might not help them. If successful, this research could pave the way for personalised arthritis care across the NHS, making sure people get the most effective treatment right from the start.

Key takeaways

Tests whether joint tissue samples can predict which arthritis drug works best for each person.
Compares two standard, approved NHS biologic medicines: sarilumab and etanercept.
Requires a small, numbed joint biopsy guided by ultrasound.
Open to adults with active rheumatoid arthritis who need to move on from standard tablet treatments.
Lasts about 16 weeks, including regular 4-weekly check-ups and a safety follow-up.

Who may be eligible?

This trial is designed for adults aged 18 and older who have active rheumatoid arthritis. To be considered, your arthritis must currently be causing moderate to high levels of inflammation, with at least three swollen joints.

You should also have already tried at least one conventional arthritis medicine (such as methotrexate) for three months or longer without getting enough improvement. This means your condition has reached the stage where NHS guidelines recommend stepping up to an advanced biologic treatment.

In addition, you must have an inflamed joint that is suitable for a small ultrasound-guided biopsy, and you must be willing to attend regular clinic visits and have routine health checks, such as blood tests.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

You are aged 18 or older.
You have a confirmed diagnosis of rheumatoid arthritis.
You currently have active joint swelling (at least three swollen joints).
You have tried standard arthritis tablets (like methotrexate) for at least 3 months without enough relief.
You are willing to have a minor joint biopsy and attend regular clinic visits.

Answer every question to see your result.

What does participation involve?

Taking part in the study lasts roughly 16 weeks in total. At the start, you will attend a clinic appointment to check your health and undergo an ultrasound-guided biopsy of one of your swollen joints. For this, a doctor numbs your joint with a local anaesthetic and takes a tiny tissue sample using a slender needle.

You will then be prescribed either sarilumab or etanercept, both of which are given as regular injections under the skin. Half of the participants will receive the drug predicted to work best by their biopsy results, while the other half will receive a drug chosen by chance. You will visit the clinic every four weeks for 12 weeks so the team can monitor your symptoms and check your blood. Finally, there is a follow-up safety visit roughly 30 days after your treatment finishes.

Potential risks and benefits

Taking part may improve your arthritis symptoms, although this cannot be guaranteed. Your participation will provide vital information that could help doctors match future patients with the right treatment much faster. Both medicines are already approved and widely used in the NHS, but they can cause mild injection site redness or slightly increase the risk of common infections. The joint biopsy is carried out using local anaesthetic to minimise discomfort, though your joint may feel a little tender or bruised for a day or two. Blood tests may also cause minor, temporary bruising. You are free to leave the trial at any point, and your standard NHS care will continue as normal.

Locations (14)

Mile End Hospital
Approximate
London, England
Manchester Royal Infirmary
Approximate
Manchester, England
Guys and St Thomas' NHS Foundation Trust
City only
London, England
Kings College Hospital
Approximate
London, England
Università degli Studi del Piemonte Orientale
Approximate
Novara, Italy
Policlinico Duilio Casula AOU Cagliari
Unverified
Cagliari, Italy
Cliniques Universitaire Saint LUC - Rhumatologie
Unverified
Bruxelles, Belgium
Hospital de Santa Maria
Unverified
Lisboa, Portugal
Hospital Clinic Barcelona
Unverified
Barcelona, Spain
Maimónides Biomedical Research Institut of Córdoba (IMIBIC)
Unverified
Córdoba, Spain
IRCCS Istituto Clinico Humanitas
Unverified
Milan, Italy
AOU di Padova
Unverified
Padova, Italy

Common questions

What is an RNA biomarker?

RNA is a natural substance in your cells that carries genetic instructions. In this study, RNA biomarkers are patterns in your joint tissue that act like clues, showing which biological pathways are active in your arthritis.

Does the joint biopsy hurt?

The area is completely numbed with a local anaesthetic before the procedure starts. You may feel a brief sting from the numbing injection and some pressure during the biopsy, followed by mild tenderness for a short time afterwards.

Are the study medicines new or experimental?

No. Both sarilumab and etanercept are well-tested, approved treatments already used routinely across the NHS for people with rheumatoid arthritis.

Will taking part cost me anything?

No, all study medications, tests, and clinical appointments related to the trial are provided free of charge.

What happens if my joints do not get better during the trial?

Your health is the top priority. The medical team monitors you closely, and if your arthritis worsens or does not improve, your doctor can step in and change your treatment plan.

How to find out more

Louise Warren

emrclinicaltrials@qmlists.qmul.ac.uk +44 (0)20 7882 8191 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.