Study of Etanercept Monotherapy vs Methotrexate Monotherapy for Maintenance of Rheumatoid Arthritis Remission

A Randomized Withdrawal Double-blind Study of Etanercept Monotherapy Compared to Methotrexate Monotherapy for Maintenance of Remission in Subjects With Rheumatoid Arthritis

The purpose of this study is to evaluate the efficacy of etanercept monotherapy compared to methotrexate monotherapy on maintenance of remission in participants with rheumatoid arthritis (RA) who were on etanercept plus methotrexate therapy.

This is a multicenter, randomized withdrawal, double-blind controlled study in participants with rheumatoid arthritis on etanercept plus methotrexate therapy who are in very good disease control for 6 months prior to study entry. The study will consist of a 30-day screening period, a 24-week open label run-in period, a 48-week double-blind treatment period and a 30-day safety follow-up period.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: etanercept pre-filled syringe subcutaneous injection; Drug: Oral methotrexate; Dietary supplement: Folic acid (non-investigational product); Drug: Placebo for etanercept subcutaneous injection; Drug: Placebo for methotrexate

• Study Type: Interventional
• Enrollment (Actual): 371
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1425
    • Research Site
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • Research Site
  • Plovdiv, Bulgaria, 4002
    • Research Site
  • Sofia, Bulgaria, 1784
    • Research Site
  • Sofia, Bulgaria, 1612
    • Research Site
  • Sofia, Bulgaria, 1505
    • Research Site
• Canada
  • Quebec, Canada, G1V 3M7
    • Research Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3N 0K6
      • Research Site
  • Nova Scotia
    • Sydney, Nova Scotia, Canada, B1S 3N1
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1Y2
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H2L 1S6
      • Research Site
    • Rimouski, Quebec, Canada, G5L 8W1
      • Research Site
    • Trois-Rivieres, Quebec, Canada, G8Z 1Y2
      • Research Site
• Czechia
  • Praha 2, Czechia, 128 50
    • Research Site
  • Uherske Hradiste, Czechia, 686 01
    • Research Site
• France
  • Bordeaux Cedex, France, 33076
    • Research Site
  • Cahors Cedex, France, 46005
    • Research Site
  • Montpellier cedex 05, France, 34295
    • Research Site
  • Orleans cedex 2, France, 45067
    • Research Site
  • Paris, France, 75010
    • Research Site
• Germany
  • Berlin, Germany, 14059
    • Research Site
  • Frankfurt am Main, Germany, 60590
    • Research Site
  • Hildesheim, Germany, 31134
    • Research Site
  • Leipzig, Germany, 04103
    • Research Site
  • Püttlingen, Germany, 66346
    • Research Site
• Greece
  • Athens, Greece, 11527
    • Research Site
  • Athens, Greece, 12462
    • Research Site
  • Athens, Greece, 14561
    • Research Site
  • Heraklion, Greece, 71110
    • Research Site
  • Thessaloniki, Greece, 54636
    • Research Site
  • Thessaloniki, Greece, 56429
    • Research Site
• Hungary
  • Budapest, Hungary, 1036
    • Research Site
  • Budapest, Hungary, 1023
    • Research Site
  • Veszprem, Hungary, 8200
    • Research Site
• Italy
  • Bari, Italy, 70124
    • Research Site
  • Catania, Italy, 95124
    • Research Site
  • Firenze, Italy, 50139
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Reggio Emilia, Italy, 42123
    • Research Site
  • Roma, Italy, 00128
    • Research Site
  • Verona, Italy, 37126
    • Research Site
• Mexico
  • Chihuahua, Mexico, 31000
    • Research Site
  • Baja California Norte
    • Mexicali, Baja California Norte, Mexico, 21100
      • Research Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44650
      • Research Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64020
      • Research Site
• Poland
  • Bydgoszcz, Poland, 85-168
    • Research Site
  • Karwiany, Poland, 52-200
    • Research Site
  • Sopot, Poland, 81-759
    • Research Site
  • Stalowa Wola, Poland, 37-450
    • Research Site
• Portugal
  • Coimbra, Portugal, 3000-075
    • Research Site
  • Lisboa, Portugal, 1649-035
    • Research Site
  • Lisboa, Portugal, 1050-034
    • Research Site
  • Ponte de Lima, Portugal, 4990-041
    • Research Site
• South Africa
  • Western Cape
    • Panorama, Western Cape, South Africa, 7500
      • Research Site
• Spain
  • Andalucía
    • Sevilla, Andalucía, Spain, 41009
      • Research Site
  • Castilla León
    • Salamanca, Castilla León, Spain, 37007
      • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08026
      • Research Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46017
      • Research Site
  • Galicia
    • A Coruña, Galicia, Spain, 15006
      • Research Site
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Research Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Research Site
  • País Vasco
    • Bilbao, País Vasco, Spain, 48013
      • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Research Site
    • Birmingham, Alabama, United States, 35205
      • Research Site
    • Huntsville, Alabama, United States, 35801
      • Research Site
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Research Site
    • Mesa, Arizona, United States, 85202
      • Research Site
    • Phoenix, Arizona, United States, 85037
      • Research Site
    • Scottsdale, Arizona, United States, 85258
      • Research Site
  • California
    • Escondido, California, United States, 92025
      • Research Site
    • Fontana, California, United States, 92335
      • Research Site
    • Hemet, California, United States, 92543
      • Research Site
    • Huntington Beach, California, United States, 92646
      • Research Site
    • La Jolla, California, United States, 92037
      • Research Site
    • Murrieta, California, United States, 92563
      • Research Site
    • Orange, California, United States, 92868
      • Research Site
    • Sacramento, California, United States, 95817
      • Research Site
    • Santa Maria, California, United States, 93454-6945
      • Research Site
    • Torrance, California, United States, 90502
      • Research Site
    • Tustin, California, United States, 92780
      • Research Site
    • Victorville, California, United States, 92395
      • Research Site
    • West Hills, California, United States, 91307
      • Research Site
  • Florida
    • Doral, Florida, United States, 33126
      • Research Site
    • Fort Lauderdale, Florida, United States, 33309
      • Research Site
    • Gainesville, Florida, United States, 32607
      • Research Site
    • Miami, Florida, United States, 33126
      • Research Site
    • Miami, Florida, United States, 33144
      • Research Site
    • Orlando, Florida, United States, 32806
      • Research Site
    • Palm Harbor, Florida, United States, 34684
      • Research Site
    • Pensacola, Florida, United States, 32514
      • Research Site
    • Saint Petersburg, Florida, United States, 33705
      • Research Site
    • Tampa, Florida, United States, 33613
      • Research Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Research Site
  • Idaho
    • Boise, Idaho, United States, 83702
      • Research Site
    • Meridian, Idaho, United States, 83642
      • Research Site
  • Illinois
    • Blue Island, Illinois, United States, 60406
      • Research Site
    • Skokie, Illinois, United States, 60076
      • Research Site
    • Springfield, Illinois, United States, 62703
      • Research Site
  • Indiana
    • Granger, Indiana, United States, 46530
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Research Site
    • New Orleans, Louisiana, United States, 70121
      • Research Site
  • Maryland
    • Wheaton, Maryland, United States, 20902
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
    • Detroit, Michigan, United States, 48202
      • Research Site
    • Grand Rapids, Michigan, United States, 49546
      • Research Site
    • Kalamazoo, Michigan, United States, 49008
      • Research Site
    • Lansing, Michigan, United States, 48910
      • Research Site
    • Lansing, Michigan, United States, 48917
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Research Site
    • Springfield, Missouri, United States, 65807
      • Research Site
  • New Jersey
    • Clifton, New Jersey, United States, 07012
      • Research Site
    • Freehold, New Jersey, United States, 07728
      • Research Site
    • Newark, New Jersey, United States, 07103
      • Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Research Site
  • New York
    • Brooklyn, New York, United States, 11201
      • Research Site
    • Great Neck, New York, United States, 11021
      • Research Site
    • New York, New York, United States, 10021
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Research Site
    • Greenville, North Carolina, United States, 27834
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Research Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15224
      • Research Site
    • Wynnewood, Pennsylvania, United States, 19096
      • Research Site
    • Wyomissing, Pennsylvania, United States, 19610
      • Research Site
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Research Site
    • Orangeburg, South Carolina, United States, 29118
      • Research Site
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Research Site
    • Knoxville, Tennessee, United States, 37909-1900
      • Research Site
  • Texas
    • Carrollton, Texas, United States, 75007
      • Research Site
    • Corpus Christi, Texas, United States, 78404
      • Research Site
    • Cypress, Texas, United States, 77429
      • Research Site
    • League City, Texas, United States, 77573
      • Research Site
    • Plano, Texas, United States, 75024
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
    • Webster, Texas, United States, 77598
      • Research Site
  • Virginia
    • Danville, Virginia, United States, 24541
      • Research Site

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 (Part 1, Run-In Period):

• Subjects must be adults with a history of moderate to severe rheumatoid arthritis;
• Subjects must be in very good rheumatoid arthritis disease control for ≥ 6 months and be in remission as defined by a Simplified Disease Activity Index ≤ 3.3 at screening and at the end of the run-in period.
• Subjects must be on etanercept 50 mg per week plus methotrexate therapy for ≥ 6 months prior to the start of the run-in period. The methotrexate dose must be 10 to 25 mg per week for ≥ 6 months prior to the start of the run-in period and the dose must be stable for ≥ 8 weeks prior to the start of the run-in period.
• Subject has no known history of active tuberculosis, and has a negative test for tuberculosis during screening.

Exclusion Criteria (Part 1, Run-In Period):

• Subject has used biologic disease modifying antirheumatic drug other than etanercept OR has used an oral janus kinase inhibitor ≤ 6 months prior to run-in visit 1
• Subject has any active infection (including chronic or localized infections) for which anti-infectives were indicated within 4 weeks prior to run-in visit 1.
• Subject has known alcohol addiction or dependency or uses alcohol daily.

• Subject has one or more significant concurrent medical conditions per investigator judgment, including the following:

  • poorly controlled diabetes
  • chronic kidney disease stage IIIb, IV, or V
  • symptomatic heart failure (New York Heart Association class II, III, or IV)
  • myocardial infarction or unstable angina pectoris within the past 12 months prior to randomization
  • uncontrolled hypertension
  • severe chronic pulmonary disease (eg, requiring oxygen therapy)
  • multiple sclerosis or any other demyelinating disease
  • major chronic inflammatory disease or connective tissue disease other than rheumatoid arthritis (eg, systemic lupus erythematosus with the exception of secondary Sjögren's syndrome)

Inclusion Criteria (Part 2, Treatment Period):

• SDAI ≤ 3.3 at run-in visit 3
• Subject if female and not at least 2 years postmenopausal or history of hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, has a negative urine pregnancy test at baseline (day 1).

Exclusion Criteria (Part 2, Treatment Period):

• Any clinically significant change in the Part 1 eligibility criteria during the run-in period
• SDAI > 3.3 and ≤ 11 on two consecutive visits at least two weeks apart OR SDAI > 3.3 and ≤ 11 on two or more separate visits OR SDAI > 11 at any time during the run-in period
• Subject has a clinically significant laboratory abnormality during run-in period which in the opinion of the investigator poses a safety risk, will prevent the subject from completing the study, or will interfere with the interpretation of the study results during the run-in period.

NOTE: Other inclusion/exclusion criteria may apply per protocol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label Run-In: Etanercept plus Methotrexate; Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 24 weeks. Participants also receive folic acid as standard of care.	Drug: etanercept pre-filled syringe subcutaneous injection; etanercept for injection in pre-filled syringes; Other Names: Enbrel; AMG916; Drug: Oral methotrexate; During the open-label run-in period, methotrexate will be provided as 2.5 mg tablets. During the double-blind treatment period, methotrexate will be provided as 2.5 mg capsules.; Dietary supplement: Folic acid (non-investigational product); Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care.
Experimental: Double-Blind Treatment: Methotrexate Monotherapy; Oral methotrexate 10 to 25 mg weekly plus placebo for etanercept for 48 weeks. Participants also receive folic acid as standard of care. After randomization, a participant experiencing protocol-defined disease worsening will initiate rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).	Drug: etanercept pre-filled syringe subcutaneous injection; etanercept for injection in pre-filled syringes; Other Names: Enbrel; AMG916; Drug: Oral methotrexate; During the open-label run-in period, methotrexate will be provided as 2.5 mg tablets. During the double-blind treatment period, methotrexate will be provided as 2.5 mg capsules.; Dietary supplement: Folic acid (non-investigational product); Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care.; Drug: Placebo for etanercept subcutaneous injection; etanercept placebo for injection in pre-filled syringes
Experimental: Double-Blind Treatment: Etanercept Monotherapy; Etanercept 50 mg weekly by subcutaneous injection plus placebo for methotrexate for 48 weeks. Participants also receive folic acid as standard of care. After randomization, a participant experiencing protocol-defined disease worsening will initiate rescue treatment with etanercept 50 mg QW plus methotrexate (10 to 25 mg).	Drug: etanercept pre-filled syringe subcutaneous injection; etanercept for injection in pre-filled syringes; Other Names: Enbrel; AMG916; Drug: Oral methotrexate; During the open-label run-in period, methotrexate will be provided as 2.5 mg tablets. During the double-blind treatment period, methotrexate will be provided as 2.5 mg capsules.; Dietary supplement: Folic acid (non-investigational product); Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care.; Drug: Placebo for methotrexate; methotrexate placebo capsules
Experimental: Double-Blind Treatment: Etanercept plus Methotrexate; Etanercept 50 mg weekly by subcutaneous injection plus oral methotrexate 10 to 25 mg weekly for 48 weeks. Participants also receive folic acid as standard of care. After randomization, a participant experiencing protocol-defined disease worsening will continue on the assigned treatments (as rescue treatment).	Drug: etanercept pre-filled syringe subcutaneous injection; etanercept for injection in pre-filled syringes; Other Names: Enbrel; AMG916; Drug: Oral methotrexate; During the open-label run-in period, methotrexate will be provided as 2.5 mg tablets. During the double-blind treatment period, methotrexate will be provided as 2.5 mg capsules.; Dietary supplement: Folic acid (non-investigational product); Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission (≤ 3.3) at Week 48: Etanercept Monotherapy vs. Methotrexate Monotherapy	The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With SDAI Remission (≤ 3.3) at Week 48: Etanercept and Methotrexate vs. Methotrexate Monotherapy	The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.	Week 48
SDAI Score at All Measured Timepoints	The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease.	Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in SDAI Score at All Measured Timepoints	The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3. A negative change from baseline indicates improvement.	Baseline, Week 12, Week 24, Week 36 and Week 48
Disease Activity Score (28 Joint) Calculated Using the Erythrocyte Sedimentation Rate Formula (DAS28-ESR) at All Measured Timepoints	The DAS28-ESR is a modified composite index that was designed to measure disease activity using the number of tender and swollen joints based upon a 28-joint count, ESR in mm/hr, and a 100 mm VAS measuring the participant's general health, from 0 (best) to 100 (worst). DAS28-ESR scores range from 0 to 9.4, where higher scores represent higher disease activity.	Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in DAS28-ESR at All Measured Timepoints	The DAS28-ESR is a modified composite index that was designed to measure disease activity using the number of tender and swollen joints based upon a 28-joint count, ESR in mm/hr, and a 100 mm VAS measuring the participant's general health, from 0 (best) to 100 (worst). DAS28-ESR scores range from 0 to 9.4, where higher scores represent higher disease activity. A negative change from baseline indicates improvement.	Baseline, Week 12, Week 24, Week 36 and Week 48
Disease Activity Score (28 Joint) Using the C-Reactive Protein Formula (DAS28-CRP) at All Measured Timepoints	The DAS28-CRP is a composite index that was designed to measure disease activity using the number of tender and swollen joints based upon a 28-joint count, CRP in mg/L, and a 100 mm VAS measuring the participant's general health from 0 (best) to 100 (worst). DAS28-CRP scores range from 0 to 9.4, where higher scores represent higher disease activity.	Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in DAS28-CRP at All Measured Timepoints	The DAS28-CRP is a composite index that was designed to measure disease activity using the number of tender and swollen joints based upon a 28-joint count, CRP in mg/L, and a 100 mm VAS measuring the participant's general health from 0 (best) to 100 (worst). DAS28-CRP scores range from 0 to 9.4, where higher scores represent higher disease activity. A negative change from baseline indicates improvement.	Baseline, Week 12, Week 24, Week 36 and Week 48
Clinical Disease Activity Index (CDAI) at All Measured Timepoints	The CDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, and Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable. The CDAI score ranges from 0 to 76, where a higher score represents worse disease.	Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline in CDAI at All Measured Timepoints	The CDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, and Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable. The CDAI score ranges from 0 to 76, where a higher score represents worse disease. A negative change from baseline indicates improvement.	Baseline, Week 12, Week 24, Week 36 and Week 48
Percentage of Participants With SDAI Remission (≤ 3.3) at All Measured Timepoints	The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.	Baseline, Week 12, Week 24, Week 36 and Week 48
Percentage of Participants With Boolean Remission at All Measured Timepoints	A participant achieves Boolean remission (66/68-joint count) if all of the following criteria are met at a single timepoint: 68-joint tender joint count ≤ 1; 66-joint swollen joint count ≤ 1; CRP (mg/dL) ≤ 1; Patient's Global Assessment of Disease Activity using a VAS (where 0=no arthritis activity at all and 10=worst arthritis activity imaginable) ≤ 1.	Baseline, Week 12, Week 24, Week 36 and Week 48
Percentage of Participants With Disease Worsening	Percentage of participants who fulfilled disease-worsening criteria for the first time is presented. Disease worsening is defined as any of the following: an SDAI > 3.3 and ≤ 11 during 2 consecutive visits at least 2 weeks apart; SDAI > 3.3 and ≤ 11 on 3 or more separate visits; SDAI > 11 after randomization. The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.	Baseline, Week 12, Week 24, Week 36 and Week 48
Time to Disease Worsening	Disease worsening is defined as any of the following: an SDAI > 3.3 and ≤ 11 during 2 consecutive visits at least 2 weeks apart; SDAI > 3.3 and ≤ 11 on 3 or more separate visits; SDAI > 11 after randomization. The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.	up to Week 48
Time to Recapture SDAI Remission After Starting Rescue Treatment	In participants who receive rescue treatment during the double-blind treatment period. The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.	Between rescue and remission or Week 48, whichever comes first.
Percentage of Participants Receiving Rescue Treatment Who Experienced SDAI Remission at Week 48	The SDAI is a composite score that is based on the number of tender and swollen joints using a 28-joint count, Physician's Global Assessment of Disease Activity using a visual analog scale (VAS) where 0=no activity at all and 100=worst activity imaginable, Patient's Global Assessment of Disease Activity using a VAS where 0=no arthritis activity at all and 100=worst arthritis activity imaginable, and C-reactive protein (CRP) in mg/dL. The SDAI score ranges from 0 to 86, with higher scores representing worse disease. SDAI remission was defined as a score of ≤ 3.3.	Week 48

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Curtis JR, Trivedi M, Haraoui B, Emery P, Park GS, Collier DH, Aras GA, Chung J. Defining and characterizing sustained remission in patients with rheumatoid arthritis. Clin Rheumatol. 2018 Apr;37(4):885-893. doi: 10.1007/s10067-017-3923-z. Epub 2017 Dec 9.
• Curtis JR, Emery P, Karis E, Haraoui B, Bykerk V, Yen PK, Kricorian G, Chung JB. Etanercept or Methotrexate Withdrawal in Rheumatoid Arthritis Patients in Sustained Remission. Arthritis Rheumatol. 2021 May;73(5):759-768. doi: 10.1002/art.41589. Epub 2021 Mar 24.
• Curtis JR, Stolshek B, Emery P, Haraoui B, Karis E, Kricorian G, Collier DH, Yen PK, Bykerk VP. Effects of Disease-Worsening Following Withdrawal of Etanercept or Methotrexate on Patient-Reported Outcomes in Patients With Rheumatoid Arthritis: Results From the SEAM-RA Trial. J Clin Rheumatol. 2023 Jan 1;29(1):16-22. doi: 10.1097/RHU.0000000000001893. Epub 2022 Oct 22.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2015
• Primary Completion (Actual): December 6, 2019
• Study Completion (Actual): December 6, 2019

Study Registration Dates

• First Submitted: January 12, 2015
• First Submitted That Met QC Criteria: February 23, 2015
• First Posted (Estimate): February 27, 2015

Study Record Updates

• Last Update Posted (Estimate): January 11, 2023
• Last Update Submitted That Met QC Criteria: January 9, 2023
• Last Verified: January 1, 2023

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; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Micronutrients; Vitamins; Reproductive Control Agents; Vitamin B Complex; Hematinics; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Etanercept; Methotrexate; Folic Acid
• Other Study ID Numbers: 20110186

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)