Abatacept Versus Adalimumab Head-to-Head

A Randomized, Head-to-Head, Single-Blind Study to Compare the Efficacy and Safety of Subcutaneous Abatacept Versus Subcutaneous Adalimumab, Both With Background Methotrexate, in Biologic-Naive Subjects With Rheumatoid Arthritis

The purpose of this study is demonstrate that subcutaneous abatacept is non-inferior (no worse than) to subcutaneous adalimumab in the treatment of subjects with rheumatoid arthritis who are biologic naive

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Abatacept; Drug: Adalimumab

• Study Type: Interventional
• Enrollment (Actual): 869
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, 5000
    • Local Institution
  • San Juan, Argentina, 5400
    • Local Institution
  • Tucuman, Argentina, 4000
    • Local Institution
  • Buenos Aires
    • Ciudad Autonoma, Buenos Aires, Argentina, CP1425A WC
      • Local Institution
    • Ciudad Autonoma De Beunos Aire, Buenos Aires, Argentina, 1431
      • Local Institution
    • Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina, 1015
      • Local Institution
    • Ciudad Autonoma De Buenos Aire, Buenos Aires, Argentina, C1428DQG
      • Local Institution
    • Quilmes, Buenos Aires, Argentina, 1878
      • Local Institution
  • Cordoba
    • Cordoba, Crd, Cordoba, Argentina, X5016KEH
      • Local Institution
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Local Institution
  • Tucuman
    • San Miguel De Tucuman, Tucuman, Argentina, 4000
      • Local Institution
• Canada
  • Quebec, Canada, G1V 3M7
    • Local Institution
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M3
      • Local Institution
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1Y2
      • Local Institution
  • Quebec
    • Trois-Rivieres, Quebec, Canada, G8Z 1Y2
      • Local Institution
• Chile
  • Providencia
    • Santiago, Providencia, Chile
      • Local Institution
• Peru
  • Lima, Peru
    • Local Institution
  • Lima, Peru, LIMA 11
    • Local Institution
  • Lima, Peru, LIMA 33
    • Local Institution
  • Lima, Peru, LIMA 27
    • Local Institution
  • Callao 2
    • Bellavista, Callao 2, Peru
      • Local Institution
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35205
      • Rheumatology Associates, Pc
    • Tuscaloosa, Alabama, United States, 35406
      • Clinical and Translational Research Center of Alabama, PC
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Sun Valley Arthritis Center, Ltd.
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Mercy Clinic Hot Springs Communities
  • California
    • Huntington Beach, California, United States, 92646
      • Talbert Medical Group
    • La Jolla, California, United States, 92037
      • Allergy & Rheumatology Medical Clinic, Inc.
    • Long Beach, California, United States, 90806
      • Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
    • Pasadena, California, United States, 91107
      • Irene Y. Tong
    • San Diego, California, United States, 92108
      • San Diego Arthritis Medical Clinic
    • Torrance, California, United States, 90503
      • Healthcare Partners Medical Group
    • Torrance, California, United States, 90505
      • Drs. Goldin, Nies, Klashman & Eng
    • Upland, California, United States, 91786
      • Inland Rheumatology & Osteoporosis Medical Group
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis and Rheumatic Disease Specialties
    • Gainesville, Florida, United States, 32610
      • University Of Florida College Of Medicine At Jacksonville
    • Miami, Florida, United States, 33173
      • Center for Arthritis and Rheumatic Diseases
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Research Of Florida, Inc.
    • Sarasota, Florida, United States, 34239
      • Sarasota Arthritis Research Center
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • Tamarac, Florida, United States, 33321
      • West Broward Rheumatology Associates
    • Venice, Florida, United States, 34292
      • Lovelace Scientific Resources, Inc
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Arthritis & Rheumatology of Georgia
    • Atlanta, Georgia, United States, 30342
      • Laureate Clinical Research Group
    • Gainesville, Georgia, United States, 30501
      • Arthritis Center of North Georgia
  • Idaho
    • Boise, Idaho, United States, 83702
      • St. Luke's Clinic - Rheumatology
    • Coeur D Alene, Idaho, United States, 83814
      • Coeur D'Alene Arthrit Clin
  • Illinois
    • Quincy, Illinois, United States, 62301
      • Quincy Medical Group
    • Rockford, Illinois, United States, 61107
      • Rockford Orthopedic Associates, Ltd.
  • Iowa
    • Cedar Rapids, Iowa, United States, 52401
      • Physicians Clinic of Iowa
  • Kentucky
    • Elizabethtown, Kentucky, United States, 42701
      • Center for Arthritis and Osteoporosis
    • Lexington, Kentucky, United States, 40504
      • Bluegrass Community Research, Inc.
  • Maryland
    • Cumberland, Maryland, United States, 21502
      • Klein And Associates, M.D., Pa
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Mansfield, Massachusetts, United States, 02048
      • Mansfield Health Center
  • Michigan
    • Battle Creek, Michigan, United States, 49015
      • Associated Internal Medicine Specialists
    • Kalamazoo, Michigan, United States, 49009
      • Rheumatology Pc
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Arthritis Associates Of Mississippi
  • Missouri
    • St.Louis, Missouri, United States, 63131
      • Physician Groups, Lc Dba
  • Nevada
    • Reno, Nevada, United States, 89502
      • Arthritis Center of Reno
  • New Hampshire
    • Dover, New Hampshire, United States, 03820
      • Seacoast Arthritis And Osteoporosis Center
    • Nashua, New Hampshire, United States, 03060
      • Nashua Rheumatology
  • New Mexico
    • Las Cruces, New Mexico, United States, 88011
      • Arthritis and Osteoporosis Associates of New Mexico
  • New York
    • Lake Success, New York, United States, 11042
      • North Shore Lij Health System
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • Smithtown, New York, United States, 11787
      • Rheumatology Associates of Long Island
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Rheumatology & Osteoporosis Research Asso P. A.
    • Statesville, North Carolina, United States, 28625
      • Carolina Pharmaceutical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Health Research Institute
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Sciences Institute
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • East Penn Rheumatology Associates, P.C.
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Center of Reading, LLP
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Low Country Rheumatology, PA
    • Columbia, South Carolina, United States, 29204
      • Columbia Arthritis Center, P.A.
  • Texas
    • Austin, Texas, United States, 78758
      • Lovelace Scientific Resources, Inc.
    • Dallas, Texas, United States, 75246
      • Arthritis Centers Of Texas
    • Houston, Texas, United States, 77004
      • Rheumatic Disease Clinical Research Center, LLC
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Center For Arthritis & Rheumatic Diseases, Pc
  • Washington
    • Spokane, Washington, United States, 99202
      • Rockwood Research Center
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Mountain State Clinical Research
  • Wisconsin
    • Glendale, Wisconsin, United States, 53217
      • Rheumatic Disease Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Moderate to severe Rheumatoid arthritis (RA) according to American College of Rheumatology (ACR) criteria
• Methotrexate failure
• Naive to RA biologics
• ≤5 years duration of disease
• Disease Activity Score-28 C-reactive protein (DAS28 CRP) ≥ 3.2
• Willingness to self-inject subcutaneous (SC) drug

Exclusion Criteria:

• Previous or current medical conditions that are warnings against the use of tumor necrosis factor (TNF)-blocking agents
• History of active or chronic hepatitis
• Cancer in the last 5 years
• History of severe chronic or recurrent bacterial or viral infections
• Risk of tuberculosis
• Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, Gastro-intestinal, pulmonary, cardiac, neurologic, or cerebral disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Adalimumab	Drug: Adalimumab; Syringes, Subcutaneous, 40 mg, Biweekly Subcutaneous injections, 24 months (729 days); Other Names: Humira
Active Comparator: Abatacept	Drug: Abatacept; Syringes, Subcutaneous, 125 mg/syringe for Subcutaneous, Weekly Subcutaneous injections, 24 months (729 days); Other Names: Orencia; BMS-188667

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Participants Meeting the American College of Rheumatology (ACR) Criteria of 20% Improvement (ACR20) After 12 Months of Treatment - Intent to Treat Population	Proportion(%)=number of participants meeting criteria (n) divided by number of participants who received drug (N). The ACR score indicates degree of improvement in a patient's rheumatoid arthritis (RA), based on guidelines set forth by the ACR and represents a percentage. To qualify a ACR20 score, patient must have >=20% fewer tender joints and >=20% fewer swollen joints and show 20% improvement from baseline in at least 3 of: patient overall assessment of his/her RA, physician global assessment of the patient's RA, patient self-assessment of pain, patient self-assessment of physical functioning, and results of an erythrocyte sedimentation rate or C-reactive protein (CRP) test (to assess inflammation). Baseline was Day 1. Randomization was stratified using screening Disease Activity Score-28 (DAS28) CRP, a composite of 4 variables: number of tender joints/28, number of swollen joints/28, CRP in mg/L and participant assessment of disease activity with visual analogue scale.	Day 1 to Day 365

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With Local Injection Site Reactions Adverse Events (Pre-specified) Reported During 12 Month Period - ITT Population	n=number of participants with a pre-specified local injection site reaction event, N=number of participants at risk. Proportion (%) = n/N. 12 Months includes data up to 56 days post last dose of the first 12 months Period or start of the first dose of second 12 months period.	Day 1 to 12 Months
Incidence Rate of Local Injection Site Reactions (Pre-specified) Reported During 24 Month Period - ITT Population	Incidence Rate: (incidence/100 person-years) = number of participants with event * 100 /exposure (person-years) Exposure (person-years) = the sum over all participants of the exposure per participant in the 24 months (censored at the time of first occurrence of AE) expressed in days, divided by 365.25. The 24 Month Period includes data up to 56 days post the last dose in the 24 month period. Poisson distribution used to construct the 95% CIs.	Day 1 to Day 729
Proportion of Participants Without Radiographic Progression in Total Score Less Than or Equal to the Smallest Detectable Change (SDC) From Baseline to Months 12 and 24 Using Modified Van Der Heijde Total Sharp Score (mSvdHS) - ITT Population	Plain radiographs of hands and feet taken at baseline (BL), Day 365, and Day 729. BL and Day 365 radiographs were re-read concurrent with Day 729 films by readers blinded to sequence and treatment (a second pre-specified reading campaign). SDC defined as amount of change for which anything smaller could not be reliably distinguished from random error in measurement of simultaneously read films. Non-progression defined: change from BL (Day 1, prior to dosing) in total score less than, equal to (<=) SDC(2.2). Proportion n/m (%)=number meeting criteria (n); number analyzed (m). SDC calculated as SD/sqrt(2)*1.96/sqrt(2)with standard deviation (SD) of paired differences of change from BL in total score between 2 readers; squared root(sqrt). mSvdHS=summary of erosion severity in 32 hand and 12 foot joints. Hand joints scored 0 to 5; foot joints 0 to 10 with 0=no erosion and higher numbers indicating greater erosion severity. BL: radiographic data within 14 days or less of first dose.	Baseline to Day 729
Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 12 Months of Treatment - ITT Population	Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, all hospitalized infections. Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post-last dose of first 12 months or start of first dose of second 12 months); denominator was overall total exposure (person-years) within this period, calculated as sum over all participants of exposure (in days) divided by 365.25. The resulting incidence rate was multiplied by 100 to express rate per 100 person-years. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE is a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.	Day 1 to Day 365
Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 24 Months of Treatment - ITT Population	Pre-specified opportunistic infections include: pneumonia, tuberculosis, herpes zoster, combined opportunistic infections, and all hospitalized infections. Incidence Rate: incidence/100 person-years: numerator was number of unique events within this period (up to 56 days post the last dose of the 24 Months period); denominator was overall total exposure (person-years) within this period, which was calculated as the sum over all participants of exposure (in days) divided by 365.25. The resulting incidence rate was multiplied by 100 to express the rate per 100 person-years. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE is a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.	Day 1 to Day 729
Proportion of Participants With Induction of Autoantibodies During the 12 Months and 24 Months Periods - ITT Population	The induction of autoantibodies was defined as participant's antinuclear antibodies (ANA) or anti-double stranded deoxyribonucleic acid (dsDNA) converting from a negative status at baseline to a positive status at a post-baseline measurement time point (Day 365 or Day 729). Proportion (%) = n/m, where n=number of participants with positive ANA or dsDNA at a time point and m=number of participants who had negative ANA or dsDNA at baseline. Blood samples were first tested for ANA by indirect fluorescent assay using HEp-2 Cell Line Substrate, and when positive, samples were further tested for anti-dsDNA by indirect fluorescent assay using Crithidia Luciliae Substrate.	Day 1 to Day 729

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Keystone EC, Ahmad HA, Yazici Y, Bergman MJ. Disease activity measures at baseline predict structural damage progression: data from the randomized, controlled AMPLE and AVERT trials. Rheumatology (Oxford). 2020 Aug 1;59(8):2090-2098. doi: 10.1093/rheumatology/kez455.
• Jabado O, Maldonado MA, Schiff M, Weinblatt ME, Fleischmann R, Robinson WH, He A, Patel V, Greenfield A, Saini J, Galbraith D, Connolly SE. Differential Changes in ACPA Fine Specificity and Gene Expression in a Randomized Trial of Abatacept and Adalimumab in Rheumatoid Arthritis. Rheumatol Ther. 2022 Apr;9(2):391-409. doi: 10.1007/s40744-021-00404-x. Epub 2021 Dec 8.
• Fleischmann R, Weinblatt M, Ahmad H, Maldonado MA, Alemao E, Ye J, Schiff M. Efficacy of Abatacept and Adalimumab in Patients with Early Rheumatoid Arthritis With Multiple Poor Prognostic Factors: Post Hoc Analysis of a Randomized Controlled Clinical Trial (AMPLE). Rheumatol Ther. 2019 Dec;6(4):559-571. doi: 10.1007/s40744-019-00174-7. Epub 2019 Oct 22.
• Fleischmann R, Connolly SE, Maldonado MA, Schiff M. Brief Report: Estimating Disease Activity Using Multi-Biomarker Disease Activity Scores in Rheumatoid Arthritis Patients Treated With Abatacept or Adalimumab. Arthritis Rheumatol. 2016 Sep;68(9):2083-9. doi: 10.1002/art.39714.
• Schiff M, Weinblatt ME, Valente R, Citera G, Maldonado M, Massarotti E, Yazici Y, Fleischmann R. Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration. RMD Open. 2016 Apr 19;2(1):e000210. doi: 10.1136/rmdopen-2015-000210. eCollection 2016.
• Fleischmann R, Weinblatt ME, Schiff M, Khanna D, Maldonado MA, Nadkarni A, Furst DE. Patient-Reported Outcomes From a Two-Year Head-to-Head Comparison of Subcutaneous Abatacept and Adalimumab for Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2016 Jul;68(7):907-13. doi: 10.1002/acr.22763.
• Sokolove J, Schiff M, Fleischmann R, Weinblatt ME, Connolly SE, Johnsen A, Zhu J, Maldonado MA, Patel S, Robinson WH. Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial. Ann Rheum Dis. 2016 Apr;75(4):709-14. doi: 10.1136/annrheumdis-2015-207942. Epub 2015 Sep 10.
• Schiff M, Weinblatt ME, Valente R, van der Heijde D, Citera G, Elegbe A, Maldonado M, Fleischmann R. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis. 2014 Jan;73(1):86-94. doi: 10.1136/annrheumdis-2013-203843. Epub 2013 Aug 20.
• Weinblatt ME, Schiff M, Valente R, van der Heijde D, Citera G, Zhao C, Maldonado M, Fleischmann R. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum. 2013 Jan;65(1):28-38. doi: 10.1002/art.37711.

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: June 29, 2009
• First Submitted That Met QC Criteria: June 29, 2009
• First Posted (Estimate): June 30, 2009

Study Record Updates

• Last Update Posted (Estimate): February 4, 2014
• Last Update Submitted That Met QC Criteria: January 3, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Adalimumab; Abatacept
• Other Study ID Numbers: IM101-235