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

NCT ID: NCT02373813

Last Updated: 2023-01-11

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

371 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-02-20

Study Completion Date

2019-12-06

Brief Summary

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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.

Detailed Description

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Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

etanercept pre-filled syringe subcutaneous injection

Intervention Type DRUG

etanercept for injection in pre-filled syringes

Oral methotrexate

Intervention Type DRUG

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.

Folic acid (non-investigational product)

Intervention Type DIETARY_SUPPLEMENT

Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care.

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).

Group Type EXPERIMENTAL

etanercept pre-filled syringe subcutaneous injection

Intervention Type DRUG

etanercept for injection in pre-filled syringes

Oral methotrexate

Intervention Type DRUG

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.

Placebo for etanercept subcutaneous injection

Intervention Type DRUG

etanercept placebo for injection in pre-filled syringes

Folic acid (non-investigational product)

Intervention Type DIETARY_SUPPLEMENT

Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care.

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).

Group Type EXPERIMENTAL

etanercept pre-filled syringe subcutaneous injection

Intervention Type DRUG

etanercept for injection in pre-filled syringes

Oral methotrexate

Intervention Type DRUG

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.

Placebo for methotrexate

Intervention Type DRUG

methotrexate placebo capsules

Folic acid (non-investigational product)

Intervention Type DIETARY_SUPPLEMENT

Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care.

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).

Group Type EXPERIMENTAL

etanercept pre-filled syringe subcutaneous injection

Intervention Type DRUG

etanercept for injection in pre-filled syringes

Oral methotrexate

Intervention Type DRUG

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.

Folic acid (non-investigational product)

Intervention Type DIETARY_SUPPLEMENT

Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care.

Interventions

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etanercept pre-filled syringe subcutaneous injection

etanercept for injection in pre-filled syringes

Intervention Type 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.

Intervention Type DRUG

Placebo for etanercept subcutaneous injection

etanercept placebo for injection in pre-filled syringes

Intervention Type DRUG

Placebo for methotrexate

methotrexate placebo capsules

Intervention Type DRUG

Folic acid (non-investigational product)

Folic acid 5 to 7 mg per week as per investigator judgment or according to local standard of care.

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Enbrel AMG916

Eligibility Criteria

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Inclusion Criteria

* 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.


* 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

* 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)


* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Research Site

Birmingham, Alabama, United States

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Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Glendale, Arizona, United States

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Mesa, Arizona, United States

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Phoenix, Arizona, United States

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Scottsdale, Arizona, United States

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Escondido, California, United States

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Fontana, California, United States

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Hemet, California, United States

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Huntington Beach, California, United States

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La Jolla, California, United States

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Murrieta, California, United States

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Orange, California, United States

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Sacramento, California, United States

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Santa Maria, California, United States

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Torrance, California, United States

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Tustin, California, United States

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Victorville, California, United States

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West Hills, California, United States

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Doral, Florida, United States

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Fort Lauderdale, Florida, United States

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Gainesville, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Palm Harbor, Florida, United States

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Pensacola, Florida, United States

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St. Petersburg, Florida, United States

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Tampa, Florida, United States

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Lawrenceville, Georgia, United States

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Boise, Idaho, United States

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Meridian, Idaho, United States

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Blue Island, Illinois, United States

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Skokie, Illinois, United States

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Springfield, Illinois, United States

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Granger, Indiana, United States

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Baton Rouge, Louisiana, United States

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New Orleans, Louisiana, United States

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Wheaton, Maryland, United States

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Ann Arbor, Michigan, United States

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Detroit, Michigan, United States

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Grand Rapids, Michigan, United States

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Kalamazoo, Michigan, United States

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Lansing, Michigan, United States

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Lansing, Michigan, United States

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Springfield, Missouri, United States

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St Louis, Missouri, United States

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Clifton, New Jersey, United States

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Freehold, New Jersey, United States

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Newark, New Jersey, United States

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Albuquerque, New Mexico, United States

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Brooklyn, New York, United States

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Great Neck, New York, United States

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New York, New York, United States

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Charlotte, North Carolina, United States

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Greenville, North Carolina, United States

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Oklahoma City, Oklahoma, United States

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Duncansville, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Wynnewood, Pennsylvania, United States

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Wyomissing, Pennsylvania, United States

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Charleston, South Carolina, United States

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Orangeburg, South Carolina, United States

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Jackson, Tennessee, United States

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Knoxville, Tennessee, United States

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Carrollton, Texas, United States

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Corpus Christi, Texas, United States

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Cypress, Texas, United States

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League City, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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Webster, Texas, United States

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Danville, Virginia, United States

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Buenos Aires, , Argentina

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Plovdiv, , Bulgaria

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Plovdiv, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Winnipeg, Manitoba, Canada

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Sydney, Nova Scotia, Canada

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Hamilton, Ontario, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Rimouski, Quebec, Canada

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Trois-Rivières, Quebec, Canada

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Prague, , Czechia

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Uherské Hradiště, , Czechia

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Bordeaux, , France

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Cahors, , France

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Montpellier, , France

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Orléans, , France

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Paris, , France

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Berlin, , Germany

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Frankfurt am Main, , Germany

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Hildesheim, , Germany

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Leipzig, , Germany

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Püttlingen, , Germany

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Heraklion, , Greece

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Thessaloniki, , Greece

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Thessaloniki, , Greece

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Budapest, , Hungary

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Budapest, , Hungary

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Veszprém, , Hungary

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Bari, , Italy

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Catania, , Italy

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Florence, , Italy

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Napoli, , Italy

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Reggio Emilia, , Italy

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Roma, , Italy

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Verona, , Italy

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Mexicali, Baja California Norte, Mexico

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Guadalajara, Jalisco, Mexico

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Monterrey, Nuevo León, Mexico

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Chihuahua City, , Mexico

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Bydgoszcz, , Poland

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Karwiany, , Poland

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Sopot, , Poland

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Stalowa Wola, , Poland

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Coimbra, , Portugal

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Lisbon, , Portugal

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Lisbon, , Portugal

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Ponte de Lima, , Portugal

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Panorama, Western Cape, South Africa

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Seville, Andalusia, Spain

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Bilbao, Basque Country, Spain

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Salamanca, Castille and León, Spain

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Barcelona, Catalonia, Spain

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A Coruña, Galicia, Spain

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Majadahonda, Madrid, Spain

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El Palmar, Murcia, Spain

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Valencia, Valencia, Spain

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Countries

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United States Argentina Bulgaria Canada Czechia France Germany Greece Hungary Italy Mexico Poland Portugal South Africa Spain

References

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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.

Reference Type BACKGROUND
PMID: 29224127 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33205906 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36459119 (View on PubMed)

Curtis JR, Emery P, Kricorian G, Yen PK, Collier DH, Bykerk V, Haraoui B. Factors Associated With Maintenance of Remission Following Change From Combination Therapy to Monotherapy in Patients With Rheumatoid Arthritis. J Rheumatol. 2023 Sep;50(9):1114-1120. doi: 10.3899/jrheum.2022-1008. Epub 2023 Apr 15.

Reference Type DERIVED
PMID: 37061234 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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20110186

Identifier Type: -

Identifier Source: org_study_id

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