Upadacitinib for Rheumatoid Arthritis

(SELECT-COMPARE Trial)

Recruiting at 369 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must be taking: Methotrexate

Must not be taking: JAK inhibitors

Disqualifiers: Adalimumab, Inadequate bDMARD response, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

1629 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study was to assess efficacy, including inhibition of radiographic progression, and safety with upadacitinib versus placebo and versus an active comparator, adalimumab, in adults with with moderately to severely active rheumatoid arthritis (RA) who are on a stable background of methotrexate (MTX and who have an inadequate response to MTX.

Will I have to stop taking my current medications?

You will need to stop taking all conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) except for methotrexate (MTX). If you have been on a biological disease-modifying anti-rheumatic drug (bDMARD), a washout period (time without taking certain medications) is required.

What data supports the effectiveness of the drug Upadacitinib for treating rheumatoid arthritis?

Upadacitinib has shown positive results in phase III trials for treating rheumatoid arthritis, leading to its approval in the USA for patients who do not respond well to methotrexate. It has demonstrated efficacy in improving patient-reported outcomes compared to placebo and adalimumab. ^{1 2 3 4 5}

Is upadacitinib safe for humans?

Upadacitinib has a generally good safety profile but may increase the risk of herpes zoster (shingles) and should not be used with certain other medications. It is not recommended for people with active tuberculosis, serious infections, active cancer, or severe liver problems. Safety monitoring continues in long-term studies. ^{1 6 7 8 9}

How is the drug Upadacitinib different from other rheumatoid arthritis treatments?

Upadacitinib is unique because it is an oral medication that selectively inhibits Janus kinase 1 (JAK-1), which helps reduce inflammation in rheumatoid arthritis. It has shown superior effectiveness compared to some other treatments like adalimumab and abatacept, especially in patients who did not respond well to methotrexate or other biologic drugs. ^{1 2 7 10 11}

Research Team

AbbVie Inc.

Principal Investigator

AbbVie

Eligibility Criteria

Adults with moderately to severely active rheumatoid arthritis who have been on a stable dose of methotrexate but haven't responded well to it. Participants must have at least 6 swollen and tender joints, evidence of bone erosion or positive RA markers, and may have had limited exposure to one other RA drug (not adalimumab). Those with other joint diseases or previous JAK inhibitor use are excluded.

Inclusion Criteria

I have 6 or more swollen and tender joints.

I have tried only one bDMARD (not adalimumab) for my condition and either couldn't tolerate it or used it for less than 3 months.

I have stopped taking all rheumatic disease drugs except for methotrexate.

Exclusion Criteria

I have previously taken JAK inhibitor medications.

I have tried adalimumab or similar medications without enough improvement.

I have a history of joint disease, but not RA. Secondary Sjogren's Syndrome is okay.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive randomized treatment with upadacitinib, placebo, or adalimumab for up to 48 weeks, with potential switches based on response criteria

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term extension

Participants continue study treatment as assigned at the end of Period 1 for up to 5 years, with ongoing assessment of joint improvement

Up to 5 years

Treatment Details

Interventions

• Adalimumab
• Placebo for Adalimumab
• Placebo for Upadacitinib
• Upadacitinib

Trial Overview The trial is testing the effectiveness and safety of Upadacitinib compared to a placebo and Adalimumab in adults with rheumatoid arthritis. All participants are already taking Methotrexate. The goal is to see if Upadacitinib can better reduce joint inflammation and prevent further damage.

Participant Groups

Group I: Upadacitinib Experimental Treatment 3 Interventions

Participants were to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were to be switched to 40 mg adalimumab eow. At Week 26 remaining participants who did not achieve low disease activity (defined as CDAI ≤ 10) were to be switched to 40 mg adalimumab eow until Week 48. Participants who complete Period 1 will continue to receive the same treatment assigned at the end of Period 1 (15 mg upadacitinib QD or 40 mg adalimumab eow) for up to 5 years in Period 2.

Group II: Adalimumab Active Control 3 Interventions

Participants were to receive placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were to be switched to 15 mg upadacitinib orally QD. At Week 26 remaining participants who did not achieve low disease activity (defined as Clinical Disease Activity Index \[CDAI\] ≤ 10) were to be switched to 15 mg upadacitinib orally QD until Week 48. Participants who complete Period 1 will continue to receive the same treatment assigned at the end of Period 1 (15 mg upadacitinib QD or 40 mg adalimumab eow) for up to 5 years in Period 2.

Group III: Placebo followed by ABT-494 Placebo Group 3 Interventions

Participants were to receive placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were to be switched to 15 mg upadacitinib orally QD. At Week 26, all remaining participants were to be switched to 15 mg upadacitinib QD until Week 48 (end of Period 1). Participants who complete Period 1 will continue to receive 15 mg upadacitinib orally QD for up to 5 years in Period 2.

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

Approved in European Union as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis
• Ulcerative colitis
• Crohn's disease

Approved in United States as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis
• Ulcerative colitis
• Crohn's disease

Approved in Canada as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis

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

Findings from Research

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 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]

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]

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 3209 patients, upadacitinib (15 mg daily) showed a comparable risk of major adverse cardiovascular events (MACE), malignancy (excluding non-melanoma skin cancer), and venous thromboembolism (VTE) when compared to adalimumab in patients with rheumatoid arthritis at higher cardiovascular risk.

However, upadacitinib was associated with higher rates of serious infections, herpes zoster, and non-melanoma skin cancer compared to the other treatments, indicating a need for careful monitoring in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme. Fleischmann, R., Curtis, JR., Charles-Schoeman, C., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Upadacitinib: First Approval. [2020]

2. New Zealand pubmed.ncbi.nlm.nih.gov

The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan. [2022]

3. England 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Upadacitinib improves patient-reported outcomes vs placebo or adalimumab in patients with rheumatoid arthritis: results from SELECT-COMPARE. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis. [2022]

6. Spain pubmed.ncbi.nlm.nih.gov

Upadacitinib tartrate in rheumatoid arthritis. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Upadacitinib for Patients with Rheumatoid Arthritis: A Comprehensive Review. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Upadacitinib in Rheumatoid Arthritis: A Benefit-Risk Assessment Across a Phase III Program. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Safety of upadacitinib in Latin American patients with rheumatoid arthritis: an integrated safety analysis of the SELECT phase 3 clinical program. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis. [2021]