Safety and Efficacy of AMG 827 in Subjects With RA | NCT01059448

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo Q2WK / 210 mg AMG 827 Q2WK	Experimental	Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.	Drug: AMG 827
70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Experimental	Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.	Drug: AMG 827
140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	Experimental	Participants who were administered 140 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2, and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.	Drug: AMG 827
210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Experimental	Participants who were administered 210 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2, and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
AMG 827	Drug	AMG 827 210 mg	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK 210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK 70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With a Treatment-emergent Adverse Event (TEAE)	A TEAE was defined as an event that occurred after the first dose date and before the end of study date in study 20090402; or an event that was already present prior to the initiation of the investigational product (i.e. present at study 20090402) baseline but worsened in either frequency or severity after the first dose date and before the end of study date in study 20090402. TEAEs also included serious treatment-emergent adverse events and clinically significant changes from baseline in hematology, chemistry and urinalysis profiles and clinically significant changes in vital sign measurements.	Day 1 to Week 52 of study 20090402
Number of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response	An ACR 20 response was defined as at least a 20% improvement from baseline in both tender/painful and swollen joint counts, and a 20% improvement or more in at least 3 of the following 5 criteria: physician global assessment of disease activity (PGA), subject global assessment of disease activity (SGA), participant global assessment of joint pain, participant self-assessment of disability (Health Assessment Questionnaire, HAQ-DI), and acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever had a bigger improvement. Participants were excluded from analysis if an ACR 20 response could not be determined due to missing component data. Baseline refers to the baseline in parent study 20090061.	Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.
Number of Participants Who Achieved an ACR 50 Response	An ACR 50 response was defined as at least a 50% improvement from baseline in both tender/painful and swollen joint counts, and a 50% improvement or more in at least 3 of the following 5 criteria: PGA, SGA, participant global assessment of joint pain, participant self-assessment of disability (HAQ-DI), and acute phase reactant: ESR or CRP, whichever had a bigger improvement. Participants were excluded from analysis if an ACR 50 response could not be determined due to missing component data. Baseline refers to the baseline in parent study 20090061.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject has provided informed consent.
Subject was randomized into study 20090061 and completed the week 16 evaluation.
Negative test for hepatitis B virus (HBV) surface antigen, hepatitis C virus (HCV) antibody, and/or human immunodeficiency virus (HIV) in subjects if clinically indicated (eg, known recent exposure) in the opinion of the investigator.
Subject must test negative for Tuberculosis.

Exclusion Criteria:

Subject had any SAE reported during 20090061 that was considered to be related to IP.
Subject is currently experiencing an infection of CTCAE grade 2 (if requiring oral antibiotics) or higher. Subject is ineligible until the infection is resolved in the opinion of the investigator.
For subjects with > 4 weeks between the week 16 visit of 20090061 and the planned first IP dose in 20090402, subject has laboratory abnormalities at screening, including:
Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT); >1.5x upper limit of normal)
Serum total bilirubin ≥1.5 mg/dL
Hemoglobin < 11 g/dL
Platelet count < 125,000 /mm3
White blood cell count < 3,000 cells/mm3
Absolute neutrophil count < 2000/mm3
Estimated creatinine clearance < 50 mL/min (Cockroft-Gault formula, central lab will calculate value and provide to sites)
Subject has a significant concurrent medical conditions, including:
Type 1 diabetes
Poorly controlled type 2 diabetes (Hemoglobin A1c > 8.5)
Symptomatic heart failure (New York Heart Association class II, III, or IV)
Myocardial infarction within the last year
Current or history of unstable angina pectoris within the last year
Uncontrolled hypertension as defined by resting blood pressure > 150/90 mmHg prior to first IP dose (confirmed by a repeat assessment)
Severe chronic pulmonary disease (eg, requiring oxygen therapy)
Major chronic inflammatory disease or connective tissue disease other than rheumatoid arthritis (eg, systemic lupus erythematosus), with the exception of secondary Sjögren's syndrome
Multiple sclerosis or any other demyelinating disease
Active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma, or history of cancer (except successfully treated in situ cervical cancer or squamous or basal cell carcinoma of the skin)
Any condition that, in the opinion of the investigator, might cause this study to be detrimental to the subject
Subject is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to the subject's last study visit including the follow-up period.
Female subject is not willing to abstain from sexual intercourse or use 2 highly effective forms of birth control for the duration of the study and at least 40 days after the last dose (except women at least 3 years postmenopausal or surgically sterile). Highly effective methods of birth control for women include but are not limited to birth control pills, Depo Provera® injections, contraceptive implants, or occlusive cap (barrier method) in combination with barrier methods used by the man.
Male subject is not willing to abstain from sexual intercourse or use 2 highly effective forms of birth control for the duration of the study, plus an additional 16 weeks after the last dose (except for men who are surgically sterile or whose female partners are at least 3 years postmenopausal or surgically sterile). Highly effective methods of birth control include but are not limited to a condom in combination with hormonal birth control or barrier methods used by the woman.
Male subject (including vasectomised males) with a pregnant female partner is not willing to use effective methods to ensure that an unborn child is not exposed to AMG 827 via semen. Effective methods to ensure that an unborn child is not exposed to AMG 827 via semen include condoms or abstinence.
Subject has used any of the following within 14 days prior to IP initiation
Non-biologic disease-modifying anti-rheumatic drugs (DMARD) other than as allowed in 20090061
Intra-articular, intramuscular, or intravenous corticosteroids, including adrenocorticotropic hormone
Subject has used any of the following within 3 months prior to IP initiation
Leflunomide
Live vaccines
Commercially available or experimental biologic DMARD except for AMG 827
Subject has received gold therapy within 6 months prior to IP initiation.
Subject received another investigational agent (other than AMG 827) or participated in an investigational device study subsequent to 20090061.
Other investigational procedures are excluded.

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Scottsdale	Arizona	85258	United States
Research Site

Label	URL
AmgenTrials clinical trials website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
BG001	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
BG002	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	Participants who were administered 140 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2, and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
BG003	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 210 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2, and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
BG004	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With a Treatment-emergent Adverse Event (TEAE)

A TEAE was defined as an event that occurred after the first dose date and before the end of study date in study 20090402; or an event that was already present prior to the initiation of the investigational product (i.e. present at study 20090402) baseline but worsened in either frequency or severity after the first dose date and before the end of study date in study 20090402.

TEAEs also included serious treatment-emergent adverse events and clinically significant changes from baseline in hematology, chemistry and urinalysis profiles and clinically significant changes in vital sign measurements.

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Posted

Count of Participants

Participants

Day 1 to Week 52 of study 20090402

ID	Title	Description
OG000	Placebo Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG001	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG002	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	Participants who were administered 140 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2, and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG003	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 210 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2, and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.

Units	Counts
Participants	OG00049 OG00155 OG00253 OG003

Title

Denominators

Categories

Title	Measurements
	OG00028 OG00132 OG00231 OG003

Primary

Number of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response

An ACR 20 response was defined as at least a 20% improvement from baseline in both tender/painful and swollen joint counts, and a 20% improvement or more in at least 3 of the following 5 criteria: physician global assessment of disease activity (PGA), subject global assessment of disease activity (SGA), participant global assessment of joint pain, participant self-assessment of disability (Health Assessment Questionnaire, HAQ-DI), and acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever had a bigger improvement. Participants were excluded from analysis if an ACR 20 response could not be determined due to missing component data.

Baseline refers to the baseline in parent study 20090061.

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Posted

Count of Participants

Participants

Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

ID	Title	Description
OG000	Placebo Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG001	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK

Primary

Number of Participants Who Achieved an ACR 50 Response

An ACR 50 response was defined as at least a 50% improvement from baseline in both tender/painful and swollen joint counts, and a 50% improvement or more in at least 3 of the following 5 criteria: PGA, SGA, participant global assessment of joint pain, participant self-assessment of disability (HAQ-DI), and acute phase reactant: ESR or CRP, whichever had a bigger improvement. Participants were excluded from analysis if an ACR 50 response could not be determined due to missing component data.

Baseline refers to the baseline in parent study 20090061.

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Posted

Count of Participants

Participants

Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

ID	Title	Description
OG000	Placebo Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG001	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.

Primary

Number of Participants Who Achieved an ACR 70 Response

An ACR 70 response was defined as at least a 70% improvement from baseline in both tender/painful and swollen joint counts, and a 70% improvement or more in at least 3 of the following 5 criteria: PGA, SGA, participant global assessment of joint pain, participant self-assessment of disability (HAQ-DI), and acute phase reactant: ESR or CRP, whichever had a bigger improvement. Participants were excluded from analysis if an ACR 70 response could not be determined due to missing component data.

Baseline refers to the baseline in parent study 20090061.

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Posted

Count of Participants

Participants

Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

ID	Title	Description
OG000	Placebo Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG001	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.

Primary

Change From Baseline in Disease Activity Score 28 Joint (DAS28) Score

The DAS28 is a composite score that is based on a 28-joint count (using 28 tender and 28 swollen joints), ESR, and SGA. The following formula was used where T/P28 and SW28 represent the tender and swollen 28 joint counts, respectively. The 28 joint counts include 10 proximal interphalangeal, 10 metacarpophalangeal, 2 wrist, 2 elbow, 2 shoulder, and 2 knee joints.

DAS28 = 0.56 √T/P28 + 0.28 √SW28 + 0.7 x ln (ESR) +0.014 x SGA.

DAS28 score ranged from 0 to 10, where a higher score represented higher disease activity. A negative change from baseline indicated a reduction in disease activity.

Baseline refers to the baseline in parent study 20090061.

FAS - All analyzable participants who were treated with at least 1 dose of AMG 827.

Posted

Mean

Standard Deviation

Score on a Scale

Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

ID	Title	Description
OG000	Placebo Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG001	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.

Primary

Number of Participants With a DAS28 Score < 2.6

DAS28 = 0.56 √T/P28 + 0.28 √SW28 + 0.7 x ln (ESR) +0.014 x SGA.

DAS28 score ranged from 0 to 10, where a higher score represented higher disease activity. A score of <2.6 indicated disease activity remission.

1 participant in the Arm "Placebo Q2WK / 210 mg AMG 827 Q2WK" was missing baseline data for DAS28.

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Posted

Count of Participants

Participants

Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

ID	Title	Description
OG000	Placebo Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG001	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.

Primary

DAS28 Score at All Measured Timepoints

DAS28 = 0.56 √T/P28 + 0.28 √SW28 + 0.7 x ln (ESR) +0.014 x SGA.

DAS28 score ranged from 0 to 10, where a higher score represented higher disease activity.

1 participant in the Arm "Placebo Q2WK / 210 mg AMG 827 Q2WK" was missing baseline data for DAS28.

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Posted

Mean

Standard Deviation

Score on a Scale

Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

ID	Title	Description
OG000	Placebo Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG001	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.

Primary

CRP Levels at All Measured Timepoints

All blood samples were taken before the dose of IP was administered. Blood samples were processed and sent to the central laboratory. The central laboratory were responsible for completing assessments.

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Posted

Mean

Standard Deviation

Milligrams per Liter (mg/L)

Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

ID	Title	Description
OG000	Placebo Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG001	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG002	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK

Primary

ESR at All Measured Timepoints

All blood samples were taken before the dose of IP was administered. ESR was performed locally at each site and the ESR data was submitted to the central laboratory.

FAS - All analyzable participants who were treated with at least one dose of AMG 827.

Posted

Mean

Standard Deviation

millimeters per hour (mm/hr)

Baseline of parent study 20090061 to Week 2, 4, 8, 12, 16, 20, 24, 36 and 48 of study 20090402.

ID	Title	Description
OG000	Placebo Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered matching placebo in parent study 20090061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG001	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.
OG002	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo / AMG 827 210 mg Q2WK	Participants who were administered matching placebo in parent study 2009061 and were administered 210 mg subcutaneous (SC) AMG 827 at Day 1, Week 1, Week 2, and every other week thereafter (Q2WK). Participants also received weekly intramuscular, oral or SC doses of methotrexate.	2	49	15	49
EG001	70 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 70 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2 and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.	5	55	18	55
EG002	140mg AMG 827 Q2WK / 210mg AMG 827 Q2WK	Participants who were administered 140 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2, and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.	1	53	19	53
EG003	210 mg AMG 827 Q2WK / 210 mg AMG 827 Q2WK	Participants who were administered 210 mg AMG 827 in parent study 20090061 and were administered 210 mg SC AMG 827 at Day 1, Week 1, Week 2, and Q2WK thereafter. Participants also continued to receive weekly intramuscular, oral or SC doses of methotrexate and folic acid or folate.	0	54	22	54

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dysphagia	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected55 at risk EG0020 affected53 at risk EG0030 affected54 at risk
Gastritis	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected55 at risk EG0020 affected53 at risk EG003
Oesophageal achalasia	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected55 at risk EG0020 affected53 at risk EG003
Chest pain	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected49 at risk EG0010 affected55 at risk EG0020 affected53 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected55 at risk EG0020 affected53 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected49 at risk EG0010 affected55 at risk EG0020 affected53 at risk EG003
Pneumonia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected49 at risk EG0010 affected55 at risk EG0020 affected53 at risk EG003
Traumatic brain injury	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected55 at risk EG0020 affected53 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected49 at risk EG0010 affected55 at risk EG0021 affected53 at risk EG003
Completed suicide	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected55 at risk EG0020 affected53 at risk EG003
Nephrotic syndrome	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected55 at risk EG0020 affected53 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vertigo	Ear and labyrinth disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected55 at risk EG0021 affected53 at risk EG0033 affected54 at risk
Conjunctivitis	Eye disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected49 at risk EG0013 affected55 at risk EG0020 affected53 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected49 at risk EG0014 affected55 at risk EG0021 affected53 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected49 at risk EG0011 affected55 at risk EG0020 affected53 at risk EG003
Injection site pain	General disorders	MedDRA 14.0	Systematic Assessment	EG0005 affected49 at risk EG0011 affected55 at risk EG0022 affected53 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected49 at risk EG0014 affected55 at risk EG0024 affected53 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0005 affected49 at risk EG0013 affected55 at risk EG0027 affected53 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected49 at risk EG0011 affected55 at risk EG0021 affected53 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0004 affected49 at risk EG0013 affected55 at risk EG0022 affected53 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected49 at risk EG0011 affected55 at risk EG0023 affected53 at risk EG003
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected49 at risk EG0013 affected55 at risk EG0024 affected53 at risk EG003
Headache	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected49 at risk EG0014 affected55 at risk EG0023 affected53 at risk EG003

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases