Abatacept vs Adalimumab for Rheumatoid Arthritis

Not currently recruiting at 186 trial locations

Overseen By David Ridley, Site 0084

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must be taking: Methotrexate

Disqualifiers: Autoimmune diseases, Infections, Immunodeficiency, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, abatacept (Orencia) and adalimumab (Humira), to determine which better aids individuals with early rheumatoid arthritis (RA) who haven't responded well to methotrexate. Participants will receive either abatacept or adalimumab, alongside methotrexate, to identify the most effective combination. The trial seeks individuals with RA symptoms for less than a year, who are taking methotrexate, and have a specific positive blood test result for RA. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires participants to have been on a stable dose of methotrexate for at least 4 weeks before joining. It doesn't specify if you need to stop other medications, but you must not have used certain other RA treatments before.

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

Research has shown that both abatacept and adalimumab, when combined with methotrexate, are generally safe for people with rheumatoid arthritis.

For abatacept, studies indicate it is well tolerated, with side effects similar to those of a placebo. Long-term data suggest it remains safe over five years, with patients typically handling it well without many serious problems. The risk of serious infections is similar to other treatments in this category.

Adalimumab with methotrexate also has a strong safety record. Over four years, this combination has remained safe and effective. Initially, the side effects were similar to those seen with a placebo, and this pattern continued over time. Even when methotrexate doses increased, the safety remained strong.

Overall, previous studies have shown both treatments to be well-tolerated, suggesting they are relatively safe options for managing rheumatoid arthritis. ^{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 unique advantages over existing therapies. Abatacept works by selectively modulating a key part of the immune system, specifically targeting T-cell activation, which is different from many standard treatments that broadly suppress the immune system. Adalimumab, in combination with methotrexate, is already well-known for its effectiveness, but this study explores the benefits of switching to abatacept after initial treatment. This approach might offer a more tailored and effective long-term strategy for managing rheumatoid arthritis, possibly enhancing patient outcomes with fewer side effects.

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

This trial will compare the effectiveness of two treatment regimens for rheumatoid arthritis. Participants in one arm will receive Abatacept combined with Methotrexate. Studies have shown that abatacept, when used with methotrexate, is consistently safe and can effectively manage rheumatoid arthritis over the long term. Many patients experience significant pain relief, with some reporting a 40% reduction in pain. Research also indicates that abatacept can help reduce joint inflammation for many people.

In another arm, participants will initially receive Adalimumab combined with Methotrexate, followed by a switch to Abatacept with Methotrexate. Studies show that adalimumab, when combined with methotrexate, benefits a large number of rheumatoid arthritis patients. After four years, many patients see significant improvement, with some experiencing clinical remission, meaning their symptoms are very low or gone. Long-term use, up to 10 years, has shown effective disease control and improved quality of life. Both treatments have strong evidence supporting their effectiveness in managing rheumatoid arthritis symptoms. ^{2 3 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

Adults with early rheumatoid arthritis (RA) that began within the last year, who have not responded well to methotrexate alone. Participants must not have used other RA drugs or treatments and should test positive for specific RA markers. They need at least 3 tender and swollen joints and a certain level of disease activity.

Inclusion Criteria

I haven't taken any RA drugs except for methotrexate.

My tests show high levels of Anti-CCP-2 and positive for rheumatoid factor.

Disease Activity Score 28-joint count calculated using C-reactive protein (DAS28-CRP) ≥ 3.2 at screening

Exclusion Criteria

I have or had an inflammatory joint disease that is not rheumatoid arthritis.

I am at risk for tuberculosis.

History of infection of a joint prosthesis or artificial joint

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Abatacept or Adalimumab on background Methotrexate

24 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Up to 104 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abatacept
• Adalimumab
• Methotrexate

Trial Overview The trial is testing if abatacept is more effective than adalimumab when both are taken with methotrexate in adults with early, seropositive RA who haven't had a good response to methotrexate alone. Patients will be randomly assigned to receive either abatacept or adalimumab.

How Is the Trial Designed?

Group I: Arm 2: (Adalimumab + Methotrexate) followed by (Abatacept + Methotrexate) Experimental Treatment 3 Interventions

Group II: Arm 1: Abatacept + Methotrexate Experimental Treatment 2 Interventions

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

Approved in European Union as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in United States as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis
• Psoriatic arthritis

Approved in Canada as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Approved in Japan as Orencia for:

• Rheumatoid arthritis
• Polyarticular juvenile idiopathic arthritis

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Abatacept significantly improves health outcomes in patients with rheumatoid arthritis, showing higher likelihoods of achieving American College of Rheumatology (ACR) response rates compared to placebo and other treatments, based on a meta-analysis of 13 randomized control trials involving 5978 patients.

Patients treated with abatacept experienced fewer adverse events compared to those receiving other biologic disease-modifying anti-rheumatic drugs, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. Mohamed Ahamada, M., Wu, X.[2023]

The study found that 60% of rheumatoid arthritis patients were aware of the patient alert cards (PACs) for abatacept, and those who received the PACs had significantly better knowledge about the risk of infections compared to those who did not (64% vs 46%).

Among healthcare professionals, 90% were aware of the PACs, and those who accessed the cards had a higher understanding of infection risks (91% vs 73%), indicating that PACs effectively enhance safety knowledge for both patients and healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linking process indicators and clinical/safety outcomes to assess the effectiveness of abatacept (ORENCIA) patient alert cards in patients with rheumatoid arthritis. Artime, E., Kahlon, R., Méndez, I., et al.[2021]

A systematic review of ten clinical trials found that all biological treatments for rheumatoid arthritis, including adalimumab, etanercept, infliximab, abatacept, tocilizumab, golimumab, and certolizumab pegol, were more effective than placebo, indicating their overall efficacy in patients resistant to DMARDs.

Indirect comparisons showed that these biological drugs had similar efficacy based on the ACR50 response criteria, suggesting that their choice should be based on safety and convenience rather than effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect comparison of biological treatments in refractory rheumatoid arthritis. Gallego-Galisteo, M., Villa-Rubio, A., Alegre-del Rey, E., et al.[2018]

Abatacept, used in combination with methotrexate for rheumatoid arthritis, demonstrated a safety profile similar to placebo in a study involving 2,944 patients, with comparable rates of adverse events and serious infections.

The treatment showed low levels of immunogenicity and did not increase the risk of autoimmune events or affect vaccination responses, indicating it is well-tolerated and safe for long-term use in RA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of T-cell co-stimulation modulation with abatacept in patients with rheumatoid arthritis. Sibilia, J., Westhovens, R.[2017]

Abatacept (Orencia) significantly improves symptoms of active rheumatoid arthritis and slows joint damage progression in patients who have previously been treated with other therapies, based on results from two phase III trials involving multiple centers over 6 to 12 months.

The treatment is generally well tolerated, with similar rates of serious adverse events between abatacept and placebo, although it may be less well tolerated when combined with other biologic DMARDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept. Hervey, PS., Keam, SJ.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10140217/

Sustained Remission and Outcomes with Abatacept plus ... Primary study endpoint was not met: 21.3% (48/225) of patients in the combination and 16.0% (24/150) in the abatacept placebo + methotrexate arm ...

2. orenciahcp.com orenciahcp.com/efficacy-data.html

Efficacy Data - ORENCIA® (abatacept) In controlled clinical trials, adult RA patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (63% vs 43%) ...

3. orencia.com orencia.com/about-orencia

ORENCIA® Side Effects & Rheumatoid Arthritis (RA) ... Pain was reduced by 40 points on a 100-point scale in people who took ORENCIA with methotrexate (from 67 to 27) · Pain was reduced by 20 points on a 100-point ...

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(23)02649-1/fulltext

Abatacept in individuals at high risk of rheumatoid arthritis ... The ARIAA results showed improvement in at least one of three parameters (synovitis, tenosynovitis, or osteitis) in 28 (57%) of 49 participants ...

5. jrheum.org jrheum.org/content/45/8/1085

Longterm Safety and Efficacy of Subcutaneous Abatacept ... These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10259009/

Safety outcomes in patients with rheumatoid arthritis ... Data from randomized, controlled clinical trials have shown abatacept to be well tolerated, with adverse event rates similar to those of placebo, and to have a ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0049017223001555

Infection outcomes in patients with rheumatoid arthritis ... Data from this international, observational study showed similar hospitalized infection risk for abatacept versus csDMARDs or other b/tsDMARDs.

8. orenciahcp.com orenciahcp.com/safety-data.html

Safety Data | ORENCIA® (abatacept) Longterm safety, efficacy, and inhibition of structural damage progression over 5 years of treatment with abatacept in patients with rheumatoid arthritis in the ...