What side effects are associated with this type of intervention?

Common treatments for Rheumatoid Arthritis, including JAK inhibitors like Upadacitinib, can have several side effects. JAK inhibitors are associated with an increased risk of infections, elevated liver enzymes, and changes in blood counts. Methotrexate, another common treatment, can cause liver toxicity, gastrointestinal issues, and bone marrow suppression. TNF inhibitors, such as adalimumab, may lead to injection site reactions, increased risk of infections, and potential cardiovascular issues. NSAIDs, often used for symptomatic relief, can cause gastrointestinal problems, cardiovascular risks, and renal issues. Patients should discuss these potential side effects with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

The FDA has approved several Janus kinase (JAK) inhibitors for the treatment of Rheumatoid Arthritis (RA). These include Tofacitinib, Baricitinib, and Upadacitinib. Tofacitinib was one of the first JAK inhibitors approved and has shown efficacy in reducing RA symptoms and slowing disease progression. Baricitinib has also been approved and is effective in patients with moderate to severe RA, particularly those who have had an inadequate response to other DMARDs. Upadacitinib, the focus of the current study, is another JAK inhibitor that has demonstrated significant efficacy in treating RA, especially in patients who have not responded well to TNF inhibitors. These drugs work by inhibiting the JAK-STAT signaling pathway, which plays a crucial role in the inflammatory process of RA.

What other types of research exist?

Promising alternatives to Upadacitinib for RA patients include Ruxolitinib, which has shown efficacy in alopecia areata and may have potential in RA, and other JAK inhibitors like Tofacitinib and Baricitinib. Additionally, biologic agents such as Secukinumab and Ustekinumab, which target different inflammatory pathways, are also viable options.

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Tumor Necrosis Factor (TNF) Inhibitor

Upadacitinib vs Adalimumab for Rheumatoid Arthritis (SELECT- SWITCH Trial)

Q: What is the mechanism of action of this treatment?

The most common treatments for Rheumatoid Arthritis (RA) include methotrexate, TNF inhibitors, and Janus kinase (JAK) inhibitors like upadacitinib. Methotrexate works by inhibiting the metabolism of folic acid, which reduces inflammation and slows disease progression. TNF inhibitors block the activity of tumor necrosis factor-alpha, a cytokine involved in systemic inflammation. JAK inhibitors, such as upadacitinib, interfere with the JAK-STAT signaling pathway, which is crucial for the inflammatory process in RA. By targeting these pathways, these treatments help reduce inflammation, prevent joint damage, and improve overall function and quality of life for RA patients.

Verified Trial

Phase 3

Recruiting

Research Sponsored by AbbVie

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Diagnosis of Rheumatoid Arthritis (RA) for >= 3 months based on the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for RA.

On oral or parenteral methotrexate (MTX) therapy >= 3 months and on a stable prescription of 15 to 25 mg/week (or >= 10 mg/week in participants intolerant of MTX at doses >= 15 mg/week) for >= 4 weeks prior to the first dose of study drug. In addition, all participants should take a dietary supplement of folic acid or folinic acid throughout the study participation.

Must not have

History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than Rheumatoid Arthritis (RA).

Prior exposure to any janus kinase (JAK) inhibitor.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 12

Awards & highlights

Pivotal Trial

Summary

This trial is testing two medications, upadacitinib (a daily pill) and adalimumab (an injection), for adults with rheumatoid arthritis who haven't responded to other treatments. The study aims to see which drug is safer and more effective. Both medications work by reducing inflammation through different mechanisms in the immune system. Adalimumab, an injection, has been extensively studied and used for treating rheumatoid arthritis, showing significant improvements in patients who have not responded to other treatments.

Who is the study for?

Adults with moderate to severe Rheumatoid Arthritis (RA) who haven't responded well or are intolerant to one TNF-inhibitor, excluding adalimumab. They must have been on a stable methotrexate dose for at least 3 months and meet specific criteria for joint swelling, tenderness, and inflammation levels. Not eligible if they've used adalimumab before, other non-TNF biologic treatments, had arthritis before age 17, or taken any JAK inhibitors.

What is being tested?

The trial is testing the safety and effectiveness of oral Upadacitinib against subcutaneous Adalimumab in RA patients. It's double-blinded and randomizes participants into two groups: one receives Upadacitinib with placebo injections; the other gets Adalimumab with placebo pills. The study spans across approximately 250 sites worldwide with about 480 participants.

What are the potential side effects?

Potential side effects may include infection risks due to immune system suppression by both drugs, liver enzyme elevations from Upadacitinib, injection site reactions from Adalimumab, as well as gastrointestinal issues and headaches common to many RA medications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been diagnosed with Rheumatoid Arthritis for 3 months or more.

Select...

I have been on a stable methotrexate treatment for at least 3 months and take folic or folinic acid supplements.

Select...

I have 6 or more swollen and tender joints and high levels of inflammation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I had arthritis before I was 17 or have an inflammatory joint disease that is not RA.

Select...

I have previously taken medication that targets JAK enzymes.

Select...

I have previously taken adalimumab.

Select...

I have previously used a non-TNFi biologic drug for my rheumatic disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 12

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 12

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 12 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Participants Achieving Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) <= 3.2

Secondary study objectives

Change from Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP])

Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score

Change from Baseline in Participants Assessment of Pain

+2 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Upadacitinib+ Adalimumab matching PlaceboExperimental Treatment2 Interventions

Participants will receive upadacitinib once a day along with matching placebo for adalimumab at eow (every other week) in Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1.

Group II: Adalimumab + Upadacitinib matching PlaceboExperimental Treatment2 Interventions

Participants will receive adalimumab at eow (every other week) along with matching placebo for upadacitinib once a day in Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Upadacitinib

2014

Completed Phase 3

~11250

Adalimumab

2013

Completed Phase 4

~7950

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Rheumatoid Arthritis (RA) include methotrexate, TNF inhibitors, and Janus kinase (JAK) inhibitors like upadacitinib. Methotrexate works by inhibiting the metabolism of folic acid, which reduces inflammation and slows disease progression. TNF inhibitors block the activity of tumor necrosis factor-alpha, a cytokine involved in systemic inflammation. JAK inhibitors, such as upadacitinib, interfere with the JAK-STAT signaling pathway, which is crucial for the inflammatory process in RA. By targeting these pathways, these treatments help reduce inflammation, prevent joint damage, and improve overall function and quality of life for RA patients.

Current jakinibs for the treatment of rheumatoid arthritis: a systematic review.The BeSt story: on strategy trials in rheumatoid arthritis.