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Study Comparing Upadacitinib, Placebo, and Adalimumab for Patients with Moderate to Severe Rheumatoid Arthritis on Stable Methotrexate Treatment

Verified siteRegistered drugNo placebo
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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 effects of treatments for rheumatoid arthritis, a condition that causes pain and swelling in the joints. The study involves two main treatments: Upadacitinib, also known by its code name ABT-494, which is taken as a tablet, and Adalimumab, marketed as Humira, which is given as an injection. Participants in the study will also be on a stable dose of Methotrexate, a common medication used to treat rheumatoid arthritis, but who have not responded adequately to it.

The purpose of the study is to compare the effectiveness and safety of Upadacitinib and Adalimumab against a placebo in people with moderate to severe rheumatoid arthritis. The study will be conducted in two periods. In the first period, participants will receive either Upadacitinib, Adalimumab, or a placebo to see how well these treatments work in reducing the symptoms of rheumatoid arthritis. The second period will focus on evaluating the long-term safety and effectiveness of Upadacitinib for those who complete the first period.

Participants will be monitored over a period of time to assess improvements in their condition, such as reduced joint pain and swelling, and to ensure the treatments are safe. The study aims to provide valuable information on how these treatments can help manage rheumatoid arthritis for those who have not had success with Methotrexate alone.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Joining the study

    Upon joining the study, you will be assigned to one of the treatment groups. This assignment is random, meaning it is like flipping a coin to decide which group you will be in. The groups include receiving either upadacitinib, adalimumab, or a placebo. A placebo is a substance that looks like the medicine but does not have any active ingredients.

  2. Step 2

    Treatment period 1

    During this period, you will take the assigned medication. If you are in the upadacitinib group, you will take a tablet by mouth once daily. If you are in the adalimumab group, you will receive an injection under the skin every other week. The placebo group will follow the same schedule as the upadacitinib or adalimumab group, depending on the assignment.

    This period lasts for 12 weeks. During this time, you will continue taking your regular dose of methotrexate, a medication you are already using for rheumatoid arthritis.

  3. Step 3

    Evaluation at week 12

    At the end of 12 weeks, your response to the treatment will be evaluated. This includes checking if there is a 20% improvement in your rheumatoid arthritis symptoms, known as an ACR20 response. Your doctor will also assess if you have reached a state of clinical remission, meaning your disease activity is very low.

  4. Step 4

    Treatment period 2

    If you complete the first period, you may continue into the second period of the study. This period focuses on the long-term safety and effectiveness of upadacitinib. The duration of this period will be explained to you by the study team.

  5. Step 5

    Ongoing assessments

    Throughout the study, you will have regular check-ups to monitor your health and the effects of the treatment. These assessments will include physical exams, blood tests, and questionnaires about your health and well-being.

  6. Step 6

    End of study

    At the end of your participation in the study, you will have a final evaluation. This will help determine the overall impact of the treatment on your rheumatoid arthritis.

Who can join the trial?

7 criteria

  • Must be an adult, male or female, at least 18 years old.
  • Must have been diagnosed with rheumatoid arthritis for at least 3 months.
  • Must have been taking methotrexate (MTX), a medication for rheumatoid arthritis, for at least 3 months. The dose should be stable between 15 to 25 mg per week (or at least 10 mg per week if higher doses are not tolerated) for at least 4 weeks before starting the study medication. Additionally, participants should take a dietary supplement of folic acid or folinic acid during the study.
  • Must have at least 6 swollen joints and 6 tender joints at the start of the study, and a blood test showing high-sensitivity C-reactive protein (hsCRP) levels of at least 5 mg/L, which indicates inflammation.
  • Must have at least one of the following: 3 or more bone erosions visible on an x-ray, or 1 or more bone erosions with a positive test for rheumatoid factor, or 1 or more bone erosions with a positive test for anti-cyclic citrullinated peptide (anti-CCP) autoantibodies. These are markers that help confirm rheumatoid arthritis.
  • May have been treated with only one biologic disease-modifying anti-rheumatic drug (bDMARD), except for adalimumab (ADA). This applies to up to 20% of the study participants.
  • Must have stopped taking all other conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) except for methotrexate.

Who cannot join the trial?

10 criteria

  • Patients who have a history of severe allergic reactions to any of the study medications cannot participate.
  • Patients with active infections, such as tuberculosis, cannot participate.
  • Patients with a history of cancer within the last 5 years, except for certain skin cancers, cannot participate.
  • Patients with liver disease or abnormal liver function tests cannot participate.
  • Patients with a history of blood disorders, such as low white blood cell count, cannot participate.
  • Patients who are pregnant or breastfeeding cannot participate.
  • Patients who have received certain other medications for rheumatoid arthritis recently cannot participate.
  • Patients with a history of heart disease or stroke cannot participate.
  • Patients with uncontrolled high blood pressure cannot participate.
  • Patients with a history of alcohol or drug abuse cannot participate.
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Investigated drugs

  • Upadacitinib

    is a medication being tested in this clinical trial for people with rheumatoid arthritis, a condition that causes pain and swelling in the joints. It is taken once a day and works by blocking certain enzymes in the body that lead to inflammation and joint damage. The goal of using upadacitinib is to reduce the symptoms of rheumatoid arthritis and prevent further joint damage.

  • Adalimumab

    is another medication used in this trial. It is a well-known treatment for rheumatoid arthritis and works by blocking a specific protein in the body that causes inflammation. By doing this, adalimumab helps to reduce pain and swelling in the joints, improving the quality of life for people with this condition.

  • Methotrexate

    is a medication that participants in the trial are already taking. It is a common treatment for rheumatoid arthritis and helps to slow down the disease's progression by affecting the immune system. In this trial, methotrexate is used as a background treatment, meaning it is continued alongside the new medications being tested to see if they work better together.

What is already known about the treatment

Upadacitinib – Upadacitinib is administered orally in the form of a tablet and is currently being studied in clinical trials for its effectiveness in treating rheumatoid arthritis, a condition where the immune system attacks the joints causing pain and swelling. It works by blocking specific enzymes called Janus kinases (JAKs) that are involved in the inflammatory process, helping to reduce inflammation and joint damage. Upadacitinib is classified as a JAK inhibitor and is being compared to placebo and another medication, adalimumab, to assess its safety and effectiveness in patients who do not respond well to methotrexate, a common treatment for rheumatoid arthritis.

Investigated diseases

Rheumatoid arthritis – Rheumatoid arthritis is a chronic inflammatory disorder that primarily affects the joints. It typically begins with inflammation in the small joints of the hands and feet, leading to pain, swelling, and stiffness. As the disease progresses, it can cause joint damage and deformities. The inflammation can also spread to larger joints and, in some cases, affect other organs such as the skin, eyes, and lungs. Over time, the persistent inflammation can lead to the destruction of cartilage and bone within the joint. This disease often results in reduced joint function and mobility.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2022-501017-31-00Protocol codeM14-465Estimated enrolment1 521 patientsSponsorAbbVie Deutschland GmbH & Co. KG

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