Skip to content
Clinical Trials – home
Not recruiting

Study on Methotrexate and Glucocorticoid Combination for Early Rheumatoid Arthritis, with Optional Etanercept for Non-Responders

Verified siteRegistered drugNo placebo
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on studying the effectiveness of treatments for Rheumatoid Arthritis, a condition that causes pain and swelling in the joints. The study involves a combination of medications, including Methotrexate, a commonly used drug for this condition, and a specific plan of glucocorticoids, which are a type of steroid medication. For patients who do not respond well to this initial treatment, the study explores the use of a medication called Etanercept, which is known to block a protein called tumor necrosis factor (TNF) that contributes to inflammation. The study also includes a medication called Leflunomide, which is taken orally and helps reduce joint damage and improve physical function.

The purpose of the study is to determine how effective these treatments are in helping patients achieve remission, which means reducing the symptoms of the disease to a minimal level. The study is designed to follow patients over a period of time to see how well they respond to the treatments. Initially, patients will receive the combination of Methotrexate and glucocorticoids. If they do not respond sufficiently, they may receive Etanercept for a period of up to 24 weeks. The study will monitor the patients' progress and adjust treatments as needed to find the most effective approach for each individual.

Participants in the study will be observed over a long period to assess the safety and effectiveness of the treatments. This includes a follow-up phase where patients' health and disease progression will be monitored for three years after the initial treatment phase. The study aims to provide valuable information on the best strategies for managing early Rheumatoid Arthritis and improving the quality of life for those affected by this condition.

The research process

The trial runs in 4 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial treatment phase

    The trial begins with the administration of a combination of Methotrexate and a step-down glucocorticoid regimen, known as COBRA-Slim. This phase aims to induce remission in patients with early rheumatoid arthritis.

    During this phase, the effectiveness of the treatment is monitored. If the response is insufficient, defined as not achieving a specific score on a disease activity scale within 32 weeks, further steps are taken.

  2. Step 2

    Treatment adaptation

    For patients who do not respond adequately to the initial treatment, an accelerated access to a six-month course of anti-TNF therapy is considered. The medication used is Etanercept, administered as a 50 mg solution for injection.

    This treatment is given subcutaneously, which means it is injected under the skin. The timeframe for this treatment is from week 8 up to week 32.

  3. Step 3

    Long-term evaluation

    The long-term effectiveness of the treatment is assessed over a period of 104 weeks. This involves monitoring the overall evolution of the disease burden, taking into account the speed and stability of the response.

    The primary measure used is the area under the curve of a specific disease activity score, which reflects the patient's condition over time.

  4. Step 4

    Extended follow-up

    After completing the initial 104-week period, patients may participate in a long-term observational follow-up for three years. This phase evaluates the clinical course and safety of the treatments received during the trial.

    The follow-up involves regular assessments to monitor the patient's condition and any potential side effects of the treatments.

Who can join the trial?

6 criteria

  • Have a diagnosis of Rheumatoid Arthritis (RA) as defined by specific criteria for early RA. This means the condition has been identified using guidelines from medical organizations.
  • The RA diagnosis must have been made within the last year.
  • If you are a woman who can have children, you must use a reliable method of birth control, as evaluated in regular medical practice.
  • You must be able and willing to give written informed consent, which means you agree to participate in the study after understanding what it involves.
  • You need to understand and be able to write in Dutch or French.
  • For the long-term follow-up part of the study, you must have participated in a previous study called CareRA2020 RCT, completed a specific part of it, and be able and willing to give written informed consent for this follow-up.

Who cannot join the trial?

15 criteria

  • Patients who have any other serious health conditions that could interfere with the study.
  • Patients who are currently participating in another clinical trial.
  • Patients who have had a recent infection that required treatment with antibiotics.
  • Patients who have a history of allergic reactions to the study medication or similar drugs.
  • Patients who are pregnant or breastfeeding.
  • Patients who have a history of drug or alcohol abuse.
  • Patients who have been diagnosed with cancer in the past five years.
  • Patients who have a history of heart disease or uncontrolled high blood pressure.
  • Patients who have liver or kidney problems.
  • Patients who have a history of tuberculosis or have been in contact with someone with tuberculosis.
  • Patients who have received a live vaccine within the last month.
  • Patients who have a history of blood disorders or problems with blood clotting.
  • Patients who have a history of autoimmune diseases other than **Rheumatoid Arthritis**.
  • Patients who have had a major surgery within the last three months.
  • Patients who are unable to comply with the study procedures or follow-up visits.
Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.

We usually reply within a few days

Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Trial locations

Where you can join this trial

Countries are shaded by recruitment status. Click a recruiting country to ask about joining there.

Not recruiting
Not finding your country?

Not sure what to do next?

Joining a clinical trial can seem overwhelming. We guide you step by step, so you know exactly what to expect and how we support you through the process.

See the full process and FAQ

Investigated drugs

  • Methotrexate

    is a medication used to treat rheumatoid arthritis by reducing inflammation and slowing down the progression of the disease. It is often used as a first-line treatment and works by suppressing the immune system to prevent joint damage.

  • Glucocorticoids

    are a type of steroid medication used in the COBRA-Slim regimen to quickly reduce inflammation and pain in patients with early rheumatoid arthritis. They help in achieving remission by controlling symptoms and preventing further joint damage.

  • Etanercept

    is a medication used in patients who do not respond adequately to the initial treatment. It is a type of anti-TNF therapy that helps reduce inflammation by blocking the tumor necrosis factor, a substance in the body that causes inflammation in rheumatoid arthritis.

What is already known about the treatment

  • Methotrexate

    Methotrexate is typically administered orally or by injection and is used in the treatment of rheumatoid arthritis. It is well-established in medical literature as a disease-modifying antirheumatic drug (DMARD). The main therapeutic indication is to reduce inflammation and slow the progression of rheumatoid arthritis. At the molecular level, methotrexate works by inhibiting the enzyme dihydrofolate reductase, which is involved in the synthesis of DNA, RNA, and proteins, thereby reducing the proliferation of immune cells that cause inflammation.

  • Etanercept

    Etanercept is administered via subcutaneous injection and is used for patients with rheumatoid arthritis who do not respond adequately to methotrexate alone. It is classified as a biologic response modifier and is well-documented in medical literature. The primary therapeutic indication is to reduce inflammation and halt disease progression in rheumatoid arthritis. Etanercept works by inhibiting tumor necrosis factor (TNF), a substance in the body that causes inflammation, thereby reducing the immune response that leads to joint damage.

Investigated diseases

Rheumatoid Arthritis – Rheumatoid arthritis is a chronic inflammatory disorder that primarily affects the joints. It typically causes pain, swelling, and stiffness in the joints, often starting in the hands and feet. Over time, the inflammation can lead to joint damage and deformities. The disease can also affect other parts of the body, including the skin, eyes, lungs, and blood vessels. The progression of rheumatoid arthritis can vary, with some people experiencing periods of remission and others having persistent symptoms. The exact cause of rheumatoid arthritis is not fully understood, but it is believed to involve a combination of genetic and environmental factors.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2023-510189-28-00Protocol codeS59474; KCE-16002Estimated enrolment442 patientsSponsorUZ Leuven

sourced from the EU Clinical Trials Register and site verification

Want to learn more about this trial or check if you can participate?

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.