A Long Term Extension Trial of BI 655066/ABBV-066 (Risankizumab), in Patients With Moderately to Severely Active Crohn's Disease

A treatment emergent adverse event was defined as an event that occurred or worsened on or after the first dose of study drug through 140 days after the last dose in the current study for participants not rolling over into M16-000 Sub-study 3 or until the first dose of study drug in NCT03105102. All treatment-emergent serious and nonserious adverse events were collected, whether elicited or spontaneously reported by the participant.

The Crohn's Disease Activity Index (CDAI) is a composite instrument that includes participant symptoms evaluated over 7 days (abdominal pain, stool frequency and general well-being), as well as physical and laboratory findings. These items are scored individually, weighted, and do not contribute equally to the overall score. The CDAI is derived from summing up the weighted individual scores of eight items. CDAI approximately ranges from 0 to 600 with higher scores indicating more severe disease. Clinical remission is defined as CDAI score < 150.

The Crohn's Disease Activity Index (CDAI) is a composite instrument that includes participant symptoms evaluated over 7 days (abdominal pain, stool frequency and general well-being), as well as physical and laboratory findings. These items are scored individually, weighted, and do not contribute equally to the overall score. The CDAI is derived from summing up the weighted individual scores of eight items. CDAI approximately ranges from 0 to 600 with higher scores indicating more severe disease. Clinical response is defined as CDAI score < 150 or a reduction from baseline of at least 100 points. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993).

The PRO-2 is calculated based on the sum of the weighted patient-reported subscores of CDAI for liquid or soft stool frequency [SF] plus abdominal pain [AP] in the 7 days prior to the study visit. The PRO-2 score is calculated by adding the values of the summed stool frequency scores multiplied by 2 plus the summed abdominal pain scores multiplied by 5. The SF and AP score at an assessment visit was the average of the daily values reported during the 7 days preceding the scheduled assessment visit. PRO-2 scores range from 0 to no upper limit with higher scores indicating more severe disease. Remission is defined as PRO-2 score < 75.

The PRO-2 is calculated based on the sum of the weighted patient-reported subscores of CDAI for liquid or soft stool frequency [SF] plus abdominal pain [AP] in the 7 days prior to the study visit. The PRO-2 score is calculated by adding the values of the summed stool frequency scores multiplied by 2 plus the summed abdominal pain scores multiplied by 5. The SF and AP score at an assessment visit was the average of the daily values reported during the 7 days preceding the scheduled assessment visit. PRO-2 scores range from 0 to no upper limit with higher scores indicating more severe disease. PRO-2 response is defined as a decrease from baseline of 50 points or more. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993).

CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The score ranges from 0 to 44 where higher scores indicate more severe endoscopic activity. Remission is defined as a score of 4 or less, by visit (or for participants with initial isolated ileitis a score of 2 or less).

CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The score ranges from 0 to 44 where higher scores indicate more severe endoscopic activity. Response is defined as a score of 7 or less (or for participants with initial isolated ileitis > 50% reduction from baseline). Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993).

Mucosal healing is defined as Crohn's Disease Endoscopy Index of Severity (CDEIS) ulcerations sub-score (deep ulceration, superficial ulceration, ulcerated stenosis) of 0 as evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The overall CDEIS score ranges from 0 to 44 where higher scores indicate more severe endoscopic activity.

Deep remission is defined as clinical remission (CDAI < 150) and CDEIS remission (CDEIS score of 4 or less, by visit or for participants with initial isolated ileitis a score of 2 or less).

The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). IBDQ remission is defined as IBDQ total score > 170 points.

The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). IBDQ response is defined as increase in IBDQ total score >16 points from baseline. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993).

The Crohn's Disease Activity Index (CDAI) is a composite instrument that includes participant symptoms evaluated over 7 days (abdominal pain, stool frequency and general well-being), as well as physical and laboratory findings. These items are scored individually, weighted, and do not contribute equally to the overall score. The CDAI is derived from summing up the weighted individual scores of eight items. CDAI approximately ranges from 0 to 600 with higher scores indicating more severe disease. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). A negative change from baseline indicates improvement.

The PRO-2 is calculated based on the sum of the weighted patient-reported subscores of CDAI for liquid or soft stool frequency [SF] plus abdominal pain [AP] in the 7 days prior to the study visit. The PRO-2 score is calculated by adding the values of the summed stool frequency scores multiplied by 2 plus the summed abdominal pain scores multiplied by 5. The SF and AP score at an assessment visit was the average of the daily values reported during the 7 days preceding the scheduled assessment visit. PRO-2 scores range from 0 to no upper limit with higher scores indicating more severe disease. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). A negative change from baseline indicates improvement.

CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The score ranges from 0 to 44 where higher scores indicate more severe endoscopic activity. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). A negative change from baseline indicates improvement.

SES-CD is calculated based the sum of individual segment values for four endoscopic variables (presence and size of ulcers, ulcerated surface, affected surface and presence of narrowing). Each variable in each segment is scored 0 to 3 resulting in SES-CD values ranging from 0 to 56 with higher scores indicating more severe disease. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). A negative change from baseline indicates improvement.

Participants were asked to record the frequency of liquid stools on a daily basis. The number of liquid stools in the prior 7 days was summed. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Negative values indicate improvement from baseline.

Participants were asked to rate and record daily abdominal pain on a scale of 0 to 3 [none (0), mild (1), moderate (2) and severe (3)]. The ratings in the prior 7 days were summed. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Negative values indicate improvement from baseline.

The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Positive values indicate improvement from baseline.

The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Positive values indicate improvement from baseline.

The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Positive values indicate improvement from baseline.

The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Positive values indicate improvement from baseline.

The Inflammatory Bowel Disease Questionnaire (IBDQ) measures the effects of inflammatory bowel disease on daily function and quality of life. The IBDQ consists of 32 questions which address symptoms as a result of Crohn's disease: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). Each question is answered on a scale from 1 (all the time) to 7 (none of the time); the total score ranges from 32 (worst) to 224 (best). Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Positive values indicate improvement from baseline.

Concentration of serum high-sensitivity C-reactive Protein (hs-CRP) was analyzed by a central laboratory. It is a general marker of inflammation that is sensitive to acute changes in inflammatory response, and higher levels indicate more inflammation. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Negative values indicate improvement from baseline.

Fecal calprotectin (FCP) is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation. Stool samples were analyzed by a central laboratory for fecal calprotectin levels. Baseline is defined as the last measurement prior to the first dose of the study drug in the feeder study NCT02031276 (Boehringer Ingelheim trial 1311.6/AbbVie M15-993). Negative values indicate improvement from baseline.