Upadacitinib vs Adalimumab for Rheumatoid Arthritis

(SELECT- SWITCH Trial)

Not currently recruiting at 343 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must be taking: Methotrexate

Must not be taking: JAK inhibitors

Disqualifiers: Juvenile arthritis, Non-RA inflammatory joint, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for rheumatoid arthritis, a condition that causes painful joint swelling. The study aims to evaluate the safety and effectiveness of the drug upadacitinib compared to adalimumab (also known as Humira) in individuals whose current medication isn't sufficiently effective. Participants will be randomly assigned to take either upadacitinib or adalimumab, with neither the participants nor their doctors knowing which one they receive. This trial is suitable for adults who have had rheumatoid arthritis for at least three months, are currently taking methotrexate, and have not responded well to a TNF-inhibitor. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of new treatment options.

Will I have to stop taking my current medications?

The trial requires participants to stay on a stable dose of methotrexate (MTX) throughout the study. The protocol does not specify if you need to stop other medications, but you must have been treated with a TNF inhibitor for at least 3 months before joining.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found upadacitinib to be safe for people with rheumatoid arthritis (RA). Doctors are familiar with its use in RA. The most common side effects include infections, headaches, and nausea, which are usually mild and manageable.

For adalimumab, research has shown that while it is effective, there is a higher risk of serious infections, sometimes requiring hospital stays. However, long-term studies indicate that most patients tolerate adalimumab well with careful monitoring.

Extensive studies on both treatments provide safety information that helps doctors balance the benefits and risks. Participants should discuss any concerns with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for rheumatoid arthritis because they offer potentially new approaches to managing the condition. Upadacitinib stands out due to its mechanism as a Janus kinase (JAK) inhibitor, which targets specific pathways involved in the inflammatory process, potentially offering more targeted relief compared to traditional tumor necrosis factor (TNF) inhibitors like adalimumab. Meanwhile, adalimumab is a well-established TNF inhibitor, known for effectively managing symptoms and slowing disease progression. Together, exploring the effects of upadacitinib and adalimumab could provide insights into optimizing treatment strategies for better patient outcomes.

What evidence suggests that this trial's treatments could be effective for rheumatoid arthritis?

This trial will compare Upadacitinib and Adalimumab for treating rheumatoid arthritis (RA). Research shows that Upadacitinib works well for RA, with many patients experiencing major improvements, reaching low disease activity or even remission in just 12 weeks. Long-term evidence also supports its safety and effectiveness for RA over five years. Adalimumab has successfully treated RA for over ten years, with real-world evidence indicating that patients continue to benefit when they stay on the treatment for a decade. Both Upadacitinib and Adalimumab are proven options for managing RA symptoms and improving joint function. Participants in this trial will receive either Upadacitinib with a placebo for Adalimumab or Adalimumab with a placebo for Upadacitinib. ^{6 7 8 9 10}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

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

I have RA and have been treated with a TNFi for 3 months or more but still have active symptoms, or I couldn't tolerate the TNFi.

Exclusion Criteria

I have previously taken medication that targets JAK enzymes.

I have previously taken adalimumab.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive either oral upadacitinib once daily and matching adalimumab placebo every other week, or subcutaneous adalimumab every other week and matching upadacitinib placebo once daily

12 weeks

Regular visits at a hospital or clinic

Treatment Period 2

Eligible participants continue to receive the same study treatment as assigned in Period 1

12 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adalimumab
• Upadacitinib

Trial Overview 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.

How Is the Trial Designed?

Group I: Upadacitinib+ Adalimumab matching Placebo Experimental Treatment 2 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 Placebo Experimental Treatment 2 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.

Adalimumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in United States as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis
• Hidradenitis suppurativa

Approved in Canada as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Approved in Japan as Humira for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis
• Crohn's disease
• Ulcerative colitis
• Plaque psoriasis
• Juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

In a study involving 5794 patients with rheumatoid arthritis who did not respond adequately to conventional or biologic treatments, upadacitinib at doses of 15 mg and 30 mg combined with methotrexate showed the highest efficacy in improving symptoms.

Both tofacitinib and upadacitinib treatments did not result in a significant increase in serious adverse events, indicating that these medications are relatively safe options for patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy and safety of tofacitinib and upadacitinib in patients with active rheumatoid arthritis: A Bayesian network meta-analysis of randomized controlled trials. Song, GG., Choi, SJ., Lee, YH.[2020]

In a study involving 3,685 subjects, upadacitinib (UPA) showed increased efficacy in treating rheumatoid arthritis as plasma exposure levels rose, with more patients achieving significant improvement in disease activity scores.

Safety analyses with 4,577 subjects indicated no clear trends in serious adverse events related to UPA exposure, suggesting a favorable safety profile, particularly with the 15 mg once daily dose, which provided optimal efficacy without significant additional risks compared to the higher 30 mg dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-Response Analyses of Upadacitinib Efficacy and Safety in Phase II and III Studies to Support Benefit-Risk Assessment in Rheumatoid Arthritis. Nader, A., Mohamed, MF., Winzenborg, I., et al.[2020]

In a phase 3 trial involving patients with psoriatic arthritis who did not respond to previous treatments, upadacitinib showed significant improvements in patient-reported outcomes (PROs) compared to placebo and was as effective as adalimumab, particularly in measures like the Health Assessment Questionnaire Disability Index (HAQ-DI) and the SF-36 Physical Component Summary score.

Patients treated with upadacitinib experienced rapid improvements in symptoms as early as week 2, with sustained benefits observed through week 56, indicating its efficacy in enhancing quality of life for those with psoriatic arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in Patient-Reported Outcomes in Patients with Psoriatic Arthritis Treated with Upadacitinib Versus Placebo or Adalimumab: Results from SELECT-PsA 1. Strand, V., Mease, PJ., Soriano, ER., et al.[2022]

In a study of 498 patients with rheumatoid arthritis who did not respond adequately to biologic treatments, both doses of upadacitinib (15 mg and 30 mg) significantly improved patient-reported outcomes (PROs) such as pain, disability, and overall disease activity compared to placebo.

More patients taking upadacitinib reported clinically meaningful improvements in quality of life measures, with the number needed to treat (NNT) to achieve these improvements ranging from 4 to 7, indicating that upadacitinib is effective in enhancing the well-being of patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs. Strand, V., Schiff, M., Tundia, N., et al.[2023]

Upadacitinib, a once-daily oral JAK inhibitor, showed significant efficacy in achieving remission and low disease activity in approximately 4400 rheumatoid arthritis patients across five pivotal trials, outperforming placebo and other treatments like methotrexate and adalimumab.

While upadacitinib was associated with an increased risk of herpes zoster and creatine phosphokinase elevations, its overall safety profile was comparable to that of methotrexate and adalimumab, suggesting a favorable benefit-risk balance for patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib in Rheumatoid Arthritis: A Benefit-Risk Assessment Across a Phase III Program. Conaghan, PG., Mysler, E., Tanaka, Y., et al.[2022]

In a study involving 596 patients from Central and Eastern Europe, upadacitinib 15 mg once daily showed significant efficacy in improving rheumatoid arthritis symptoms compared to placebo and adalimumab, with results maintained over 48 weeks.

While upadacitinib demonstrated clinical benefits, it also had a higher incidence of serious infections and herpes zoster compared to adalimumab, indicating a need for careful monitoring of safety in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib versus placebo or adalimumab with background methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate: a subgroup analysis of a phase III randomized controlled trial in Central and Eastern European patients. Pavelka, K., Szekanecz, Z., Damjanov, N., et al.[2022]

In a 48-week study involving patients with rheumatoid arthritis, upadacitinib 15 mg daily was found to be more effective than adalimumab or placebo in improving disease symptoms and preventing joint damage when used alongside methotrexate.

Patients who switched from adalimumab to upadacitinib due to insufficient response showed a higher rate of achieving low disease activity compared to those switching from upadacitinib to adalimumab, indicating that upadacitinib may provide better outcomes for patients not responding to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Fleischmann, RM., Genovese, MC., Enejosa, JV., et al.[2020]

In a phase IIIB/IV trial involving patients with rheumatoid arthritis who did not respond adequately to methotrexate, treatment with tofacitinib in combination with methotrexate showed significantly greater improvements in patient-reported outcomes like pain and overall disease activity compared to tofacitinib monotherapy.

All treatment groups, including tofacitinib monotherapy and combinations with methotrexate or adalimumab, demonstrated clinically meaningful improvements in patient-reported outcomes, but the differences were small, suggesting that while combination therapies may offer some benefits, the overall clinical significance may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes for tofacitinib with and without methotrexate, or adalimumab with methotrexate, in rheumatoid arthritis: a phase IIIB/IV trial. Strand, V., Mysler, E., Moots, RJ., et al.[2020]

In a 3-year study comparing upadacitinib to adalimumab in patients with rheumatoid arthritis, both treatments had similar rates of adverse events, indicating a comparable safety profile.

Upadacitinib demonstrated consistently better clinical responses than adalimumab across various endpoints, suggesting it may be a more effective long-term treatment option for managing rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis: results through 3 years from the SELECT-COMPARE study. Fleischmann, R., Mysler, E., Bessette, L., et al.[2023]

In a study involving 661 patients with rheumatoid arthritis (RA) who did not respond adequately to conventional DMARDs, upadacitinib (15 mg and 30 mg) significantly improved patient-reported outcomes such as pain, physical function, and overall disease activity after 12 weeks compared to placebo.

Patients taking upadacitinib reported clinically meaningful improvements in various measures, with the number needed to treat (NNT) for these benefits ranging from 4 to 8, indicating that a small number of patients need to be treated for one to experience significant improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT. Strand, V., Pope, J., Tundia, N., et al.[2021]

Upadacitinib, an oral JAK-1 inhibitor, received marketing approval in the USA in August 2019 for treating moderately to severely active rheumatoid arthritis after showing positive results in multinational phase III trials.

The approval was specifically for patients who had an inadequate response or intolerance to methotrexate, highlighting its role as an effective alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib: First Approval. Duggan, S., Keam, SJ.[2020]

In a 48-week study involving patients with rheumatoid arthritis who did not respond adequately to methotrexate, upadacitinib showed significant improvements in patient-reported outcomes compared to placebo and was at least as effective as adalimumab.

Patients treated with upadacitinib reported greater reductions in pain, disability, and stiffness, with more individuals achieving clinically meaningful improvements across various measures compared to those on adalimumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib improves patient-reported outcomes vs placebo or adalimumab in patients with rheumatoid arthritis: results from SELECT-COMPARE. Strand, V., Tundia, N., Bergman, M., et al.[2022]

Citations

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HUMIRA for Moderate to Severe Rheumatoid Arthritis (RA) When compared with methotrexate alone in a clinical study, more people taking HUMIRA and methotrexate saw a 20% improvement in the signs and symptoms of RA at 6 ...

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HUMIRA® (adalimumab) Safety profile Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death.

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HUMIRA® (adalimumab) injection, for subcutaneous use The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections in patients with rheumatoid arthritis (RA); ...

9. humirapro.com humirapro.com/rheumatoid-arthritis

HUMIRA® (adalimumab) for Rheumatoid Arthritis (RA) Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed ...

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Safety analyses of adalimumab (HUMIRA) in global clinical ... Conclusion. Analyses of these data demonstrate that long term adalimumab treatment is generally safe and well tolerated in patients with RA. Keywords: ...