A Study of Mirikizumab (LY3074828) in Participants With Moderately to Severely Active Ulcerative Colitis

The UNRS is a single participant reported item that measures the severity for the urgency (sudden or immediate need) to have a bowel movement in the past 24 hours using an 11-point NRS ranging from 0 (no urgency) to 10 (worst possible urgency). Higher scores indicate more severe urgency. Baseline Observation Carried Forward (BOCF) endpoint was defined as the baseline value for participants discontinued during acute phase and defined as the last non-missing observation in the treatment phase for all other randomized participants.

Time frame: Baseline, Week 12

Population: All enrolled participants who received at least one dose of study drug (regardless of whether the participant does not receive the correct treatment or otherwise does not follow the protocol) with a non-missing baseline and BOCF endpoint.

BUF is participant reported single item measure of the number of urgent bowel movements reported in the past 24 hours.

Time frame: Baseline, Week 12

Population: All enrolled participants who received at least one dose of study drug (regardless of whether the participant does not receive the correct treatment or otherwise does not follow the protocol) with a non-missing baseline and BOCF endpoint.

This outcome evaluates correlations between change from baseline in UNRS, BUF, SDT, APU, and PROs related to quality of life (QoL), functional outcomes, and UC symptoms. QoL is assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ), a 32-item patient-completed tool with four domains: bowel (score range 10-70), systemic (5-35), emotional (12-84), and social (5-35). Each item is rated on a 7-point Likert scale (1 = very severe problem, 7 = not a problem at all); The total IBDQ score is calculated by summing the scores from all four domains and total score range is 32-224 (Higher = better QoL). Functional outcomes measures: Work Productivity and Activity Impairment (WPAI) questionnaire (four scores derived: absenteeism, presenteeism, productivity loss, activity impairment; each score 0-100%, higher = greater impairment) and Generalized Anxiety Disorder-7 (GAD-7;total score range 0-21, higher = more severe anxiety)... (Continued below due to character constraint)

Time frame: Baseline, Week 12 UC symptom measures:Patient Global Rating of Severity (PGR-S)(1-6),Patient Global Impression of Change (PGI-C)(1-7),Mayo SF/RB (0-3),Abdominal pain/fatigue NRS (0-10),nocturnal stool frequency; higher=worse severity for all measures.

Population: All enrolled participants who received at least one dose of study drug and had evaluable data for this outcome (regardless of whether the participant does not receive the correct treatment or otherwise does not follow the protocol)

This outcome evaluates correlations between UNRS, BUF, SDT, APU, and patient-reported outcomes (PROs) related to quality of life (QoL), functional outcomes, and UC symptoms. QoL is assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ), a 32-item patient-completed tool with four domains: bowel (score range 10-70), systemic (5-35), emotional (12-84), and social (5-35). Each item is rated on a 7-point Likert scale (1 = very severe problem,7 = not a problem at all); The total IBDQ score is calculated by summing the scores from all four domains and total score range is 32-224 (Higher = better QoL). Functional outcomes measures: Work Productivity and Activity Impairment (WPAI) questionnaire (four scores derived: absenteeism, presenteeism, productivity loss, activity impairment; each score 0-100%, higher = greater impairment) and Generalized Anxiety Disorder-7 (GAD-7; total score range 0-21, higher = more severe anxiety)... (Continued below due to character constraint)

Time frame: Baseline to Week 12 UC symptom measures:Patient Global Rating of Severity (PGR-S)(1-6),Patient Global Impression of Change (PGI-C)(1-7),Mayo SF/RB (0-3),Abdominal pain/fatigue NRS (0-10),nocturnal stool frequency;higher=worse severity for all measures.

Population: All enrolled participants who received at least one dose of study drug and had evaluable data for this outcome (regardless of whether the participant does not receive the correct treatment or otherwise does not follow the protocol)

UNRS measures bowel urgency severity (range 0 to 10; Higher scores indicate more severe urgency). BUF measures the number of urgent bowel movements reported in the past 24 hours. SDT measures the average duration a patient could delay defecation in the past 24 hours. APU is a single item to assess participant's need to wear an adult diaper, pad or protection because of bowel urgency. This outcome evaluates the pairwise correlations between the change in correlations among four bowel urgency-related measures above.

Time frame: Baseline, Week 12

Population: All enrolled participants who received at least one dose of study drug and had evaluable data for this outcome (regardless of whether the participant does not receive the correct treatment or otherwise does not follow the protocol)

UNRS measures bowel urgency severity (range 0 to 10; Higher scores indicate more severe urgency). BUF measures the number of urgent bowel movements reported in the past 24 hours. SDT measures the average duration a patient could delay defecation in the past 24 hours. APU is a single item to assess participant's need to wear an adult diaper, pad or protection because of bowel urgency. This outcome evaluates the pairwise correlations among four bowel urgency-related measures above.

Time frame: Baseline to Week 12

Population: All enrolled participants who received at least one dose of study drug and had evaluable data for this outcome (regardless of whether the participant does not receive the correct treatment or otherwise does not follow the protocol).

Clinical remission based on MMS is defined as Stool Frequency (SF) sub score (range 0-3, higher is worse) = 0, or SF = 1 with a ≥1- point decrease from baseline, and 1. Rectal Bleeding (RB) sub score (range 0-3, higher is worse) = 0, and 2. Endoscopic sub score (ES) (range 0-3, higher is worse) = 0 or 1 (excluding friability). UNRS measures bowel urgency severity (range 0 to 10; Higher scores indicate more severe urgency) This outcome assesses the proportion of participants who achieved both a clinical response, as defined by an MMS, and an improvement of ≥3 points from baseline in a UNRS score at Week 12.

Time frame: Week 12

Population: All enrolled participants who received at least one dose of study drug (regardless of whether the participant does not receive the correct treatment or otherwise does not follow the protocol)

Clinical response based on MMS is defined as: 1. A change in the MMS of ≤ -2 points and ≤ -30% change from baseline, and 2. A change of ≤-1 point in the RB subscore (range 0-3, higher is worse) from baseline or a RB score of 0 or 1. UNRS measures bowel urgency severity (range 0 to 10; Higher scores indicate more severe urgency) This outcome measures the percentage of participants achieving both, clinical response, based on the MMS, and a UNRS score of ≥3 points of improvement from baseline at 12 weeks.

Time frame: Week 12

Population: All enrolled participants who received at least one dose of study drug (regardless of whether the participant does not receive the correct treatment or otherwise does not follow the protocol)

This outcome measures the percentage of participants who experience a clinically meaningful reduction in the frequency of bowel urgency episodes from baseline to the 12 week treatment period. Results for this outcome will be reported during final results posting.

Time frame: Baseline to Week 12

This outcome measures the percentage of participants who demonstrate a clinically meaningful improvement in SDT. Results for this outcome will be reported during final results posting.

Time frame: Week 12

The SDT is a participant-reported single item measure of the average duration a patient could delay defecation in the past 24 hours. The shortest weekly SDT is used for analysis of SDT in minutes by taking the shortest response (i.e. minimum value) available over the past 7 days, where no urgency is treated as the largest value. The SDT categories were:\<1 min, ≥1 min to \<2 min, ≥2 min to \<5 min, ≥5 min to \<15 min, and ≥15 min or no urgency. No urgency indicates participant's selected Did not feel urge to have a bowel movement in the past 24 hours for all available days in 7-day period.

Time frame: Week 12

Population: All enrolled participants who received at least one dose of study drug (regardless of whether the participant does not receive the correct treatment or otherwise does not follow the protocol)