A Study of Vedolizumab in People With Ulcerative Colitis and Crohn's Disease

AE was defined as any untoward medical occurrence in clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with the treatment. AE can therefore be any unfavourable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with use of a drug, whether or not it is considered related to the drug. A SAE was any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in significant disability or incapacity, was a congenital anomaly/birth defect or was a medically important event. An AESI (serious or nonserious) was one of scientific and medical concern specific to the compound or program.

An ADR was an AE for which there was at least a reasonable suspicion of a causal relationship between an AE and a suspected medicinal product. An unexpected ADR was an ADR with the nature, severity, or outcome which was not consistent with the product insert.

Clinical response for UC participants was defined as decrease in Simple Clinical Colitis Activity Index (SCCAI) of greater than and equal to (>=) 3 from baseline or by physician assessment of clinical response. The SCCAI consists of five colitis activity symptom items (bowel frequency per day, bowel frequency per night, urgency of defecation, blood in stool, and general well-being) along with an assessment of extracolonic manifestations. Bowel frequency per night is scored on a 0-2 scale and General well-being is scored on a 0-4 scale. The other 3 symptom scores are scored on a 0-3 scale. 1 point each is added for the presence of any extracolonic manifestation (i.e., arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis). The total overall possible scoring range was 0-19 with increasing scores being indicative of more colitis activity.

Clinical response for CD participants was defined as decrease in Harvey Bradshaw Index (HBI) of >= 3 points from baseline. HBI was composed of five clinical parameters: general well-being (0-4, where higher score means lower wellbeing), abdominal pain (0-3, higher score means more severe pain), number of liquid stools/day, abdominal mass (0-3, where higher score means presence of swelling in the abdomen), and complications (score 1 per item). Total score was the sum of individual parameters. The score ranged from a minimum score of 0 to no pre-specified maximum score as it depended on the number of liquid stools, where higher scores indicated more severe disease. The score < 5 is considered as clinical remission, 5-7 mild, 8-16 moderate, and >16 severe disease. A higher score indicated a worse outcome.

Clinical remission for UC participants was defined as decrease in SCCAI of less than and equal to (<=) 2 with no individual score > 1. The SCCAI consists of five colitis activity symptom items (bowel frequency per day, bowel frequency per night, urgency of defecation, blood in stool, and general well-being) along with an assessment of extracolonic manifestations. Bowel frequency per night is scored on a 0-2 scale and General well-being is scored on a 0-4 scale. The other 3 symptom scores are scored on a 0-3 scale. 1 point each is added for the presence of any extracolonic manifestation (i.e., arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis). The total overall possible scoring range was 0-19 with increasing scores being indicative of more colitis activity.

Clinical remission for CD participants was defined as HBI of <= 4. HBI was composed of five clinical parameters: general well-being (0-4, where higher score means lower wellbeing), abdominal pain (0-3, higher score means more severe pain), number of liquid stools/day, abdominal mass (0-3, where higher score means presence of swelling in the abdomen), and complications (score 1 per item). Total score was the sum of individual parameters. The score ranged from a minimum score of 0 to no pre-specified maximum score as it depended on the number of liquid stools, where higher scores indicated more severe disease. The score < 5 is considered as clinical remission, 5-7 mild, 8-16 moderate, and >16 severe disease. A higher score indicated a worse outcome.

Vedolizumab discontinuation was defined as ceasing vedolizumab, or a treatment gap >= 90 days between consecutive doses.

Mucosal healing was based on endoscopic evidence of no inflammation and healing of the mucosa as defined by a Mayo endoscopic sub-score of <=1 point. Full Mayo Score evaluated ulcerative colitis stage, based on four parameters: stool frequency, rectal bleeding, endoscopic evaluation, and Physician's global assessment. Each parameter of the score (including Mayo endoscopic sub-score) ranged from 0 (normal or inactive disease) to 3 (severe activity) yielding a total score of 0-12. The scores 0-2 were considered as clinical remission, 3-5 mild, 6-10 moderate, and 11-12 severe, with higher scores indicated more severe disease.

Mucosal healing was based on endoscopic evidence of no inflammation and healing of the mucosa as defined by a Simple Endoscopic Score for Crohn Disease (SES-CD) 0-2 or SES-CD <=4 and at least a 2-point reduction from baseline with no sub-score >1. SES-CD assessed the size of mucosal ulcers, ulcerated surface, endoscopic extension, and the presence and type of narrowings. Each of the four SES-CD variables was scored from 0 to 3, with the sum of scores for each variable ranging from 0 to 15 yielding a total SES-CD score of 0-60, where higher scores indicated more severe disease.

Endoscopic response was defined as decrease in Mayo endoscopic sub-score of >=1 point in UC participants. Full Mayo Score evaluated ulcerative colitis stage, based on four parameters: stool frequency, rectal bleeding, endoscopic evaluation, and Physician's global assessment. Each parameter of the score (including Mayo endoscopic sub-score) ranges from 0 (normal or inactive disease) to 3 (severe activity) yielding a total score of 0-12. The scores 0-2 are considered as clinical remission, 3-5 mild, 6-10 moderate, and 11-12 severe, where higher scores indicated more severe disease.

Endoscopic response was defined as > 50% decrease in SES-CD in CD participants. SES-CD assessed the size of mucosal ulcers, ulcerated surface, endoscopic extension, and the presence and type of narrowings. Each of the four SES-CD variables was scored from 0 to 3, with the sum of scores for each variable ranged from 0 to 15 yielding a total SES-CD score of 0-60, where higher scores indicated more severe disease.

The SIBDQ was a valid and reliable instrument used to assess quality of life in adult participants with Inflammatory Bowel Disease (IBD). It was a 10-item questionnaire that included questions on 4 domains of health-related quality of life (HRQoL): bowel systems, emotional function, social function, and systemic function and was scored on a 7-point Likert scale from 1 (severe problem) to 7 (no problems at all). A total SIBDQ score was calculated by summing the scores from each domain; the total SIBDQ score ranged from 10 (poor HRQoL) to 70 (optimum HRQoL). Higher values of SIBDQ represented a better quality of life.