RecruitingPhase IIIInterventional

Oral versus intramuscular glucocorticoids in rheumatoid arthritis

Rheumatoid arthritis causes painful, swollen joints. Long-term medicines called DMARDs help protect the joints, but they can take up to six months to start working. During this wait, doctors often prescribe steroids for quick relief. However, steroids can cause side effects such as weight gain, mood changes, and high blood sugar, so they must be used carefully. Doctors are not sure whether a short course of steroid tablets or a one-off steroid injection works better, or which dose strikes the best balance between symptom relief and side effects. The LEADER study tests four different ways of taking standard steroids in adults starting or changing their arthritis treatment. Participants are followed for six months to compare joint pain, tiredness, daily wellbeing, and side effects, helping the NHS choose the safest and most effective approach for the future.

At a glance

Status

Recruiting

Phase

Phase III

Sponsor

University of Manchester

Enrolment target

448

Start

04 Jul 2025

Estimated completion

04 Nov 2026

Rheumatoid arthritis

What is this study about?

Rheumatoid arthritis is a condition where your immune system attacks the lining of your joints, causing pain, swelling, and stiffness. Standard treatments, known as disease-modifying anti-rheumatic drugs (DMARDs), help calm the immune system and prevent joint damage. However, these medicines work slowly and can take several months to give noticeable relief.

To help bridge this gap, doctors often prescribe steroid medicines. Steroids work quickly to reduce inflammation and ease joint pain while waiting for the long-term medicine to take effect. Even though steroids are very helpful in the short term, they can cause side effects like weight gain, skin thinning, mood changes, and raised blood sugar if used for too long or at doses that are too high.

Currently, steroids can be given as a daily reducing course of tablets or as a single injection into a muscle. Doctors do not yet know which of these methods, or which dose, gives the quickest pain relief while causing the fewest unwanted effects. The LEADER trial aims to answer this question so that people with rheumatoid arthritis receive the safest, most effective care in the NHS.

Key takeaways

The study tests whether steroid tablets or an injection provide the best short-term relief for rheumatoid arthritis.
It aims to find the right dose that eases joint pain quickly with the fewest side effects.
All medicines tested are standard NHS treatments, not experimental drugs.
Participation lasts for six months and involves regular joint checks, surveys, and simple blood tests.
You are free to leave the study at any time without giving a reason.

Who may be eligible?

You may be able to join the LEADER trial if you are 18 or older and have been diagnosed with rheumatoid arthritis. You must have active symptoms right now, which means having at least three swollen joints and three tender joints. You also need to be preparing to start, switch, or increase your main long-term arthritis medication.

You will not be able to take part if you have received steroid tablets or injections in the past 28 days, or if your doctor advises against steroid treatment. The study is also not suitable for people with poorly controlled diabetes, women who are pregnant or planning a pregnancy, or anyone diagnosed with fibromyalgia or widespread chronic pain in the last six months.

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 over.
I have active rheumatoid arthritis with at least 3 tender and 3 swollen joints.
I am about to start, change, or increase a long-term arthritis medication (DMARD).
I have not had any steroid injections or tablets in the past 28 days.
I am not pregnant or trying to become pregnant.
I do not have uncontrolled diabetes or a recent fibromyalgia diagnosis.

Answer every question to see your result.

What does participation involve?

Taking part in the study lasts for about six months. You will be randomly placed by a computer into one of four treatment groups: higher-dose tablets that reduce over six weeks, lower-dose tablets that reduce over four weeks, a single higher-dose injection into your muscle, or a single lower-dose injection.

Most study checks happen during your usual clinic visits, but you will have one extra visit two weeks after starting. During the first three months and again at month six, your care team will examine your joints, ask you to fill in short surveys about pain, mood, and daily activities, and take routine blood samples. You will only need one extra blood draw for the study at your week two visit. You will also be given a simple finger-prick kit to do at home, which checks how your body's natural stress hormones are responding to the steroid.

Potential risks and benefits

Both the steroid tablets and the injection used in this study are already widely prescribed across the NHS, so their safety and side effects are well known. Common short-term side effects can include temporary mood changes, trouble sleeping, mild weight gain, or raised blood sugar. You may also feel brief discomfort at the injection site or from blood tests. Taking part may not directly improve your arthritis more than standard care, but your joints will be monitored very closely by specialists. Your participation will also help doctors understand how to give steroids more safely for future patients. You are free to leave the trial at any point without it affecting your medical care.

Locations (30)

Pennine MSK Partnership Ltd
City only
Oldham, England
University Hospitals Plymouth NHS Trust
City only
Plymouth, England
East Sussex Healthcare NHS Trust
City only
St. Leonards-on-sea, England
Eastbourne District General Hospital
Approximate
Eastbourne, England
King's College Hospital
Approximate
London, England
Mersey and West Lancashire Teaching Hospitals NHS Trust
Unverified
Prescot, England
Rochdale Infirmary
Unverified
Rochdale, England
Fairfield General Hospital
Unverified
Bury, England
Airedale NHS Foundation Trust
Unverified
Keighley, England
County Durham and Darlington NHS Foundation Trust
Unverified
Darlington, England
Barts Health NHS Trust
Unverified
London, England
Sandwell and West Birmingham Hospitals NHS Trust
Unverified
Smethwick, England

Common questions

Can I choose whether I get the tablets or the injection?

No. To make the study fair and scientifically sound, a computer randomly assigns you to one of the four groups. You must be happy to receive either the tablets or the injection to join.

Are the medications in this trial experimental?

No. Both prednisolone tablets and methylprednisolone injections are standard, fully licensed steroid treatments already used every day in the NHS.

Will I still take my regular arthritis medicines?

Yes. The steroid is a short-term 'bridge' treatment used alongside your main long-term arthritis medicine while you wait for it to take full effect.

What happens if my joint pain gets worse during the trial?

Your safety comes first. If your symptoms flare up or do not improve, your hospital rheumatology team can change or adjust your treatment as needed.

Do I have to pay for any of the study visits or tests?

No. All study-related treatments, clinic visits, and testing kits are provided free of charge through the NHS and the research programme.

How to find out more

Anne Francis

leader@ndorms.ox.ac.uk +44 1865 01865 612701 Official trial record

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