A Study in Participants With Rheumatoid Arthritis on Background Methotrexate Therapy

Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128

ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) \* 100.

Time frame: Baseline through Weeks 76 and 128

Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24

ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100.

Time frame: Baseline through Weeks 2, 4, 8, 12, 16, 20, 24

Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128

ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100.

Time frame: Baseline through Weeks 76 and 128

Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24

ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) \* 100.

Time frame: Baseline through Weeks 2, 4, 8, 12, 16, 20, 24

Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128

ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) \* 100.

Time frame: Baseline through Weeks 76 and 128

Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response

ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.

Time frame: Baseline through Week 12

ACR Percent Improvement (ACR-N)

ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in RA that characterizes percentage (%) of improvement in disease activity from baseline based on ACR core set. This index was calculated as minimum of a) % of improvement in TJC, b) % of improvement in SJC, and c) third highest percentage of improvement of remaining 5 ACR core criteria: If ≥3 components of the 5 ACR core criteria were missing, then c) was set to missing; if any of 3 components a), b), or c) were missing, then ACR-N was set to missing. Percentage of improvement was truncated to a range of -100 to 100 to minimize impact of outliers (greater scores indicate greater % improvement) and negative scores indicate a decline. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.

Time frame: Baseline through Week 12

Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)

TJC is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. SJC is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint.

Time frame: Baseline, Weeks 12 and 24

Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC

TJC is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. SJC is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint.

Time frame: Baseline, Weeks 76 and 128

Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score

The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.

Time frame: Baseline, Weeks 12 and 24

Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score

The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.

Time frame: Baseline, Weeks 76 and 128

Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP)

hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.

Time frame: Baseline, Weeks 12 and 24

Mean Change From Baseline to Weeks 76 and 128 in hsCRP

hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.

Time frame: Baseline, Weeks 76 and 128

Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR)

ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.

Time frame: Baseline, Weeks 12 and 24

Mean Change From Baseline to Weeks 76 and 128 in ESR

ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.

Time frame: Baseline, Weeks 76 and 128

Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

Physician's and Patient's Assessments of Disease Activity (DA) assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeters (mm), where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. Patient's assessment of pain due to arthritis was also assessed using a VAS that ranged from 0 (no pain) to 100 mm (worst possible pain).

Time frame: Baseline, Weeks 12 and 24

Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain

Physician's and Patient's assessments of DA assessed using a VAS that ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. Patient's assessment of pain due to arthritis assessed using a VAS that ranged from 0 (no pain) to 100 mm (worst possible pain).

Time frame: Baseline, Weeks 76 and 128

Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)

Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). DAS28-CRP=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*patient's global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity, and remission was DAS28-CRP \<2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.

Time frame: Baseline, Weeks 12 and 24

Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP

Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using visual analog scale (VAS) (patient's global VAS). DAS28-CRP=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*patient's global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP \<2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.

Time frame: Baseline, Weeks 76 and 128

Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24

EULAR28 categorizes clinical response based upon improvement since baseline in DAS modified to include the 28-joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: TJC28, SJC28, CRP, and Patient's Global Assessment of their Disease Activity (patient's global VAS). DAS28 scores range from 1.0-9.4. EULAR28 categories include: No Response (improvement in DAS28 of ≤0.6 units or post-baseline DAS28 score \>5.1 with improvement by ≤1.2 units), Moderate Response (post-baseline DAS28 ≤5.1 with improvement by \>0.6 units but ≤1.2 units or post-baseline DAS28 score \>3.2 with improvement by \>1.2 units), and Good Response (post-baseline DAS28 score ≤3.2 with improvement by \>1.2 units).

Time frame: Baseline through Weeks 12 and 24

Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128

EULAR28 categorizes clinical response based upon improvement since baseline in Disease Activity Score modified to include the 28-joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP, and Patient's Global Assessment of their Disease Activity (patient's global VAS). DAS28 scores range from 1.0-9.4. EULAR28 categories include: No Response (improvement in DAS28 of ≤0.6 units or post-baseline DAS28 score \>5.1 with improvement by ≤1.2 units), Moderate Response (post-baseline DAS28 ≤5.1 with improvement by \>0.6 units but ≤1.2 units or post-baseline DAS28 score \>3.2 with improvement by \>1.2 units), and Good Response (post-baseline DAS28 score ≤3.2 with improvement by \>1.2 units).

Time frame: Baseline, Weeks 76 and 128

Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24

Disease Activity Score (DAS) modified to include 28-joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP \[milligrams per liter (mg/L)\], and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores \<2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders.

Time frame: Baseline through Weeks 12 and 24

Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128

Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores \<2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders.

Time frame: Baseline through Weeks 76 and 128

Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness

The Investigator asked participants about the duration of their morning stiffness (in minutes) in and around the joints and recorded the duration. The Investigator asked the participants about duration of morning stiffness on the day prior to the study visit to capture actual symptoms. If morning stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses.

Time frame: Baseline, Weeks 4, 8, 12

Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores

The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains (physical functioning, bodily pain, role limitations due to physical problems and also emotional problems, general health, mental health, social functioning and vitality) and 2 component scores (PCS and MCS). The PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. The MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. Both PCS and MCS range from 0-100 with higher scores indicating better health or functioning.

Time frame: Baseline, Week 12

Mean Change From Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-sf Modified) Worst-Pain-in-the Past-24-hours Item Score

The BPI-sf modified is a self-administered questionnaire developed for the rapid assessment of pain. The BPI-sf modified provides information on the intensity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The questionnaire asks questions about pain relief, pain quality, and the participant's perception of the cause of pain. The BPI-sf modified uses a numeric rating scale from 0 ("No pain") to 10 ("Pain as bad as you can imagine"). Since pain can be quite variable over a day, the BPI-sf modified asked participants to rate their pain at the time of responding to the questionnaire (right now), and also at its worst, least and average over the last 24 hours.

Time frame: Baseline, Week 12

Mean Change From Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score

The FACIT-F Scale is a brief 13-item, symptom-specific questionnaire that specifically assesses the participant self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 ("Not at all") to 4 ("Very much") for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue.

Time frame: Baseline, Week 12

Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104

Time frame: Baseline through 24 weeks

Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104

Time frame: Baseline through 24 weeks

Mean Change From Baseline Through Week 12 in the ENSEMBLE Minimum Data Set 1.0

Time frame: Baseline, 12 weeks