CompletedNot ApplicableInterventional

Stratification of biologic therapies for rheumatoid arthritis by pathobiology

Rheumatoid arthritis causes painful, stiff, and swollen joints because the immune system mistakenly attacks healthy tissue. Standard tablets do not help everyone. When they fail, doctors often prescribe powerful targeted treatments called biologics. However, choosing the right biologic can often involve months of frustrating trial and error. This UK study investigates whether testing a tiny sample of joint tissue can help doctors predict which biologic will work best for each individual. Participants are randomly allocated to receive one of three proven medicines: etanercept, rituximab, or tocilizumab. Some are given as simple weekly injections under the skin, while another is given as a drip in hospital. The trial lasts for one year and includes monthly check-ups. A key benefit is that if your assigned medicine is not working after four months, doctors can switch you to an alternative much sooner than in standard care.

At a glance

Status

Completed

Phase

Not Applicable

Sponsor

Queen Mary University of London

Enrolment target

207

Start

15 Jun 2015

Estimated completion

31 May 2019

Rheumatoid arthritis

What is this study about?

Rheumatoid arthritis is a long-term condition that causes inflammation, pain, and stiffness in the joints. In a healthy body, immune cells produce antibodies to fight off infections. In people with rheumatoid arthritis, these immune cells become confused and start attacking healthy joints instead. Standard treatment usually begins with tablets called disease-modifying anti-rheumatic drugs (DMARDs), which calm the immune system. However, for around four in ten people, these first-line treatments do not provide enough relief.

When standard tablets fail, doctors turn to advanced medicines called biologics. Biologics work by blocking specific proteins or cells that fuel joint inflammation. There are several different types of biologics, such as etanercept, tocilizumab, and rituximab. At present, doctors cannot easily tell which one will work best for an individual patient, so finding the right treatment is often a process of trial and error that can take many months.

This study aims to change that by using 'personalised medicine'. Doctors take a tiny sample of tissue from an inflamed joint (called a synovial biopsy) to examine the pattern of inflammation under a microscope. Researchers want to see if these tissue patterns can accurately predict which biologic drug will give the best results. If successful, this research could help future patients get the right treatment straight away, preventing joint damage and unnecessary pain.

Key takeaways

Tests whether joint tissue samples can help match arthritis patients to the best medicine.
Compares three established biologic drugs: etanercept, rituximab, and tocilizumab.
For adults with active rheumatoid arthritis whose standard tablets have not worked.
Involves a small joint biopsy, regular monthly clinic visits, and one year of monitoring.
Offers a faster medicine switch at four months if your symptoms are not improving.

Who may be eligible?

This study is open to adults aged 18 and over who have active rheumatoid arthritis that has not improved enough after trying standard arthritis tablets (DMARDs). Because your previous treatments have not worked, you must meet standard NHS criteria to receive biologic therapies.

To be eligible, you need to have at least three swollen joints at the start of the study. One of these joints must have enough swelling and thickened lining so that doctors can safely and easily collect a small tissue sample for the study.

You cannot take part if you are pregnant, planning to become pregnant, or breastfeeding. Because the study medicines may harm an unborn baby, both men and women must be willing to use effective contraception throughout the study. You will also be excluded if you have any other medical conditions that make these specific biologic medicines unsafe for you.

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.

I am aged 18 or older.
I have been diagnosed with active rheumatoid arthritis.
My previous arthritis tablets (such as methotrexate) have not worked well enough.
I have at least three swollen joints right now.
I am not pregnant, not breastfeeding, and willing to use reliable contraception.

Answer every question to see your result.

What does participation involve?

If you take part, your participation will last for approximately one year. At the start, a specialist will take a small tissue sample from an inflamed joint using a gentle, minimally invasive procedure with local anaesthetic. You will then be randomly assigned by a computer to receive one of three biologic treatments. You cannot choose which drug you receive. The first group receives etanercept as a weekly injection just under the skin. The second group receives rituximab as a drip into a vein on day 1 and day 15, repeated after six months. The third group receives tocilizumab as a weekly injection under the skin. You will visit the clinic once a month for routine health checks, joint examinations, and blood tests. Researchers will assess your progress closely at 16 weeks to see if your symptoms have improved by at least 20%.

Potential risks and benefits

A major potential benefit is receiving close, regular medical monitoring throughout the year. If your assigned treatment is not helping, the trial team can switch your medicine at four months rather than waiting the usual six months required in standard NHS care. However, there are risks to consider. The joint biopsy can cause temporary soreness, bruising, bleeding, or a small risk of infection. The study medicines can also cause side effects, such as a higher risk of catching ordinary infections. In addition, if you are assigned to rituximab during the study, standard NHS guidelines may not automatically allow you to continue taking it after the trial ends. Joining is completely voluntary, and you are free to leave the trial at any time without your regular NHS care being affected.

Locations (20)

Mile End Hospital
Approximate
London, England
University Hospital of Wales
Approximate
Cardiff, Wales
Queen Elizabeth Hospital
Approximate
Birmingham, England
University College London Hospitals
City only
London, England
Freeman Hospital Newcastle
Approximate
Newcastle upon Tyne, England
Glasgow Royal Infirmary
Unverified
Glasgow, Scotland
Nuffield Orthopaedic Centre
Unverified
Oxford, England
Southampton Centre for Biomedical Research
Unverified
Southampton, England
Chapel Allerton Hospital
Unverified
Leeds, England
Manchester Royal Infirmary
Unverified
Manchester, England
Southend Hospital
Unverified
Southend, England
Basildon Hospital
Unverified
Basildon, England

Common questions

What does a joint biopsy involve?

A doctor uses a local anaesthetic to numb your joint so you do not feel sharp pain. They then use a fine needle or small tube to collect a tiny sample of the joint lining. The procedure is quick, minimally invasive, and you can go home the same day.

Can I choose which biologic medicine I receive?

No. A computer randomly decides which of the three medicines you will receive. This random allocation is essential to ensure the study results are fair and scientifically accurate.

Will I have to inject myself?

If you are assigned to etanercept or tocilizumab, you will receive simple weekly injections under the skin. The clinical team will train you or a family member to do this comfortably at home. If you receive rituximab, it will be given as a drip by a nurse in the hospital clinic.

What happens if the treatment does not work for me?

Your joints will be checked at each visit. If your symptoms have not improved by at least 20% by week 16, your care team will switch you to a different arthritis medicine two months earlier than in routine NHS practice.

Can I leave the study if I change my mind?

Yes. You have the right to withdraw from the study at any time. You do not have to give a reason, and your decision will not affect the quality of your ongoing NHS treatment.

How to find out more

Jo Peel

Official trial record

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