Abatacept vs Adalimumab for Rheumatoid Arthritis

Recruiting at 175 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

338 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the superiority in efficacy of abatacept compared with adalimumab, on background methotrexate, in adults with early, seropositive, and shared epitope-positive rheumatoid arthritis and an inadequate methotrexate response.

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.

What data supports the effectiveness of the drugs Abatacept and Adalimumab for treating rheumatoid arthritis?

Research shows that both Abatacept and Adalimumab are effective in improving symptoms of rheumatoid arthritis, such as pain and joint inflammation, especially when used with Methotrexate. Studies found that these drugs significantly improve physical function and slow joint damage compared to Methotrexate alone. ^{1 2 3 4 5}

Is abatacept safe for humans?

Abatacept (Orencia) is generally considered safe for humans with rheumatoid arthritis, with similar rates of adverse events compared to placebo. Some patients may experience mild-to-moderate reactions, and there is a low risk of serious infections or malignancies. ^{1 6 7 8 9}

How do the drugs abatacept and adalimumab differ from other rheumatoid arthritis treatments?

Abatacept (Orencia) and adalimumab (Humira) are unique in their mechanisms; abatacept works by modulating a signal needed for T-cell activation, while adalimumab targets a protein called TNF to reduce inflammation. Both can be administered subcutaneously and are used in combination with methotrexate for rheumatoid arthritis, offering options for patients who do not respond to other treatments. ^{1 10 11 12 13}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Analysis of efficacy and safety of abatacept for rheumatoid arthritis: systematic review and meta-analysis. [2023]

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

Patient-Reported Outcomes From a Two-Year Head-to-Head Comparison of Subcutaneous Abatacept and Adalimumab for Rheumatoid Arthritis. [2018]

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

Abatacept. [2018]

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

The comparative effectiveness of abatacept versus anti-tumour necrosis factor switching for rheumatoid arthritis patients previously treated with an anti-tumour necrosis factor. [2021]

5. France pubmed.ncbi.nlm.nih.gov

Meta-analysis of clinical and radiological efficacy of biologics in rheumatoid arthritis patients naive or inadequately responsive to methotrexate. [2022]

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

Safety of Abatacept Versus Placebo in Rheumatoid Arthritis: Integrated Data Analysis of Nine Clinical Trials. [2022]

7. England 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. [2021]

8. Italy pubmed.ncbi.nlm.nih.gov

Safety of T-cell co-stimulation modulation with abatacept in patients with rheumatoid arthritis. [2017]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Description of the efficacy and safety of three new biologics in the treatment of rheumatoid arthritis. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. [2022]

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

Abatacept: a review of its use in the management of rheumatoid arthritis. [2021]

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

Abatacept: A Review in Rheumatoid Arthritis. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Indirect comparison of biological treatments in refractory rheumatoid arthritis. [2018]