A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis

Percentage of Participants Achieving 50% Improvement in American College of Rheumatology Criteria (ACR50) Response at Week 12

The ACR50 response was a composite measure of clinical, laboratory, and functional assessments used to evaluate improvement in rheumatoid arthritis signs and symptoms. ACR50 responders were participants with at least 50% improvement from baseline in TJC and SJC, and at least 50% improvement in 3 of the 5 remaining core measures: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, HAQ-DI which measures participants' perceived degree of difficulty performing daily activities, and acute phase reactant as measured by hsCRP. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100.

Time frame: Week 12

Percentage of Participants Achieving 70% Improvement in American College of Rheumatology Criteria (ACR70) Response at Week 12

The ACR70 response was a composite measure of clinical, laboratory, and functional assessments used to evaluate improvement in rheumatoid arthritis signs and symptoms. ACR70 responders were participants with at least 70% improvement from baseline in TJC and SJC, and at least 70% improvement in 3 of the 5 remaining core measures: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, HAQ-DI which measures participants' perceived degree of difficulty performing daily activities, and acute phase reactant as measured by hsCRP. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) \* 100.

Time frame: Week 12

Percentage of Participants With Low Disease Activity (LDA) According to Disease Activity Score Modified to Include the 28 Diarthrodial Joint Count-High-Sensitivity C-Reactive Protein (DAS28-hsCRP) ≤3.2 at Week 12

DAS28-hsCRP LDA was defined as DAS28-hsCRP score of ≤3.2. The Disease Activity Score (DAS) based on 28 joint counts consisted of a composite numerical score derived from the following variables: tender joint count (0 to 28), swollen joint count (0 to 28), high-sensitivity C-reactive protein (hsCRP, mg/mL), and the patient's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56\*square root (sqrt) (TJC28) plus (+) 0.28\*sqrt (SJC28)+ 0.014\* participant's global assessment of disease activity+ 0.36\*natural log(hsCRP+1) + 0.96. Total Scores ranged from 1.0 to 9.4, with lower scores indicating less disease activity.

Time frame: Week 12

Percentage of Participants With Remission According to DAS28-hsCRP Score <2.6 at Week 12

DAS28-hsCRP remission is defined as DAS28-hsCRP \<2.6. DAS based on 28 joints consisted of composite numerical score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and patient's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP=0.56\*sqrt (TJC28) + 0.28\*sqrt (SJC28) + 0.014\* patient's global assessment of disease activity + 0.36\*natural log(hsCRP+1) +0.96. Total Scores ranged from 1.0-9.4, where lower scores indicated less disease activity.

Time frame: Week 12

Percentage of Participants Achieving LDA According to Clinical Disease Activity Index (CDAI) Score ≤10 at Week 12

Low disease activity was defined as a CDAI score of ≤10. CDAI is a tool for measurement of disease activity in rheumatoid arthritis that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity.

Time frame: Week 12

Percentage of Participants Achieving Remission According to CDAI Score ≤2.8 at Week 12

Remission was defined as a CDAI score of ≤2.8. CDAI is a tool for measurement of disease activity in rheumatoid arthritis that does not require a laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity). The CDAI is calculated by summing the values of the 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity.

Time frame: Week 12

Change From Baseline in DAS28-hsCRP Score at Week 12

DAS based on 28 joints consisted of composite numerical score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and patient's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP = 0.56\*sqrt (TJC28) + 0.28\*sqrt (SJC28)+ 0.014\* patient's global assessment of disease activity + 0.36\*natural log(hsCRP+1) +0.96. Total scores ranged 1.0-9.4; lower scores indicated lower disease activity. A negative change from baseline indicates improvement in condition. Least Square (LS) Mean was calculated using mixed model repeated measures (MMRM) with treatment, stratification factors, baseline value, visit, treatment-by-visit interaction as fixed factors and participant as a random factor.

Time frame: Baseline, Week 12

Change From Baseline in CDAI Score at Week 12

CDAI is a tool for measurement of disease activity in rheumatoid arthritis that does not require laboratory component and was scored by the investigative site. It integrates TJC28 (scored 0-28 with higher scores indicating higher disease activity), SJC28 (scored 0-28 with higher scores indicating higher disease activity), Patient's Global Assessment of Disease Activity (scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity), and Physician's Global Assessment of Disease Activity(scored on a visual analogue scale from 0-10 cm with higher scores indicating higher disease activity).CDAI is calculated by summing values of 4 components. CDAI scores range from 0 to 76; lower scores indicated lower disease activity. Negative change from baseline indicates improvement. LS Mean was calculated using MMRM with treatment, stratification factors, baseline value, visit, treatment-by-visit interaction as fixed factors and participant as a random factor.

Time frame: Baseline, Week 12

Change From Baseline in HAQ-DI Score at Week 12

HAQ-DI was a patient-reported questionnaire used in rheumatoid arthritis to assess physical function over the past week. It covered 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2 to 3 items. Each item is scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Any activity requiring assistance from another individual or the use of an assistive device adjusts to a minimum score of 2 to represent a more limited functional status. Total score was computed as the sum of domain scores and divided by the number of domains answered. The total score ranges from 0 to 3, with higher scores indicating greater physical limitations. LS Mean was calculated using MMRM with treatment, stratification factors, baseline value, visit and treatment-by-visit interaction as fixed effects and participant as a random effect.

Time frame: Baseline, Week 12

Minimum Observed Concentration of Peresolimab by Treatment-Emergent Anti-Drug Antibody (TE ADA) Status

Minimum observed concentration of peresolimab was assessed and stratified by Treatment-Emergent Anti-Drug Antibody (TE-ADA) status (TE ADA positive and TE ADA negative). A TE ADA evaluable participant was defined as TE ADA positive if they met the following criteria: 1. Had baseline status of ADA Not Present and at least 1 postbaseline status of ADA Present with titer ≥ 2×minimum required dilution (MRD) of the ADA assay (Treatment Induced TE ADA). The MRD of peresolimab is 1:10. 2. Had baseline and postbaseline status of ADA Present, with the postbaseline titer being 2 dilutions (4-fold) greater than the baseline titer. TE-ADA negative participants were defined as those not meeting the TE ADA positive criteria.

Time frame: Baseline through Week 12