An Open-label Study of Ozanimod in Moderate to Severe Ulcerative Colitis in Clinical Practice

An Adverse Event (AE) is any new medical problem or worsening of a preexisting condition in a study participant who receives the study treatment. It does not have to be caused by the treatment. An AE can be any unfavorable and unintended sign (such as an abnormal lab finding), symptom, or disease that happens around the time the study treatment is used, whether or not it is related to the treatment.

A Treatment Emergent Adverse Event (TEAE) is an AE that meets any of the following:

• Starts after the first dose of the study treatment (or within 84 days after stopping it) and was not present before; or
• Was already present before treatment but gets worse after the first dose (or within 84 days after stopping it); or
• Has missing onset and end dates, making it unclear whether it occurred outside the treatment-emergent period.

Participants meeting any of these conditions are counted as having at least one TEAE.

Serious Adverse Event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, is a congenital anomaly/birth defect, requires in-patient hospitalization or causes prolongation of existing hospitalization, or results in persistent/significant disability/incapacity.

Treatment Emergent Serious Adverse Event (TE SAE) is a SAE that meets any of the following:

• Starts after the first dose of the study treatment (or within 84 days after stopping it) and was not present before; or
• Was already present before treatment but gets worse after the first dose (or within 84 days after stopping it); or
• Has missing onset and end dates, making it unclear whether it occurred outside the treatment-emergent period.

Participants meeting any of these conditions are counted as having at least one TESAE.

This endpoint reports the number of participants who experienced Adverse Events of Interest (AEIs) during the study. AEIs include bradycardia, heart conduction abnormalities (second-degree and higher atrioventricular block), macular edema, malignancy, serious or opportunistic infection, pulmonary effects, hepatic effects, posterior reversible encephalopathy syndrome, progressive multifocal leukoencephalopathy (PML), and events associated with orthostatic hypotension (e.g., dizziness, lightheadedness, syncope, seizure). The Sponsor may request additional information for nonserious AEIs.

A Treatment Emergent AEI is an AEI that starts after the first dose (or within 84 days after stopping), worsens relative to baseline in this period (or within 84 days after stopping), or has missing dates making the timing unclear.

Participants meeting any of these conditions are counted as having at least one AEI.

This endpoint measures the number of participants who experienced Treatment Emergent Adverse Events (TEAEs) that resulted in discontinuation of study treatment.

An Adverse Event (AE) is any new medical problem or worsening of a preexisting condition in a study participant who receives the study treatment. It does not have to be caused by the treatment. An AE can be any unfavorable and unintended sign (such as an abnormal lab finding), symptom, or disease that happens around the time the study treatment is used, whether or not it is related to the treatment.

A TEAE is an AE that: starts after the first dose (or within 84 days after stopping) and was not present before; or was preexisting but worsens after the first dose (or within 84 days after stopping); or has missing dates that prevent determining whether it occurred outside the treatment emergent period.

Number of participants experiencing clinically significant abnormalities in laboratory testing including hematology, chemistry and urinalysis.

Clinical remission is defined as a Partial Mayo Score of ≤ 2.5.

The Partial Mayo Score is a tool that helps doctors measure how active ulcerative colitis is without using endoscopy. It combines three components:

• Stool Frequency (SF) subscore: range 0-3 (higher score = more frequent stools)
• Rectal Bleeding (RB) subscore: range 0-3 (higher score = more bleeding)
• Physician's Global Assessment (PGA): range 0-3 (higher score = worse overall condition based on physician's judgment)

The total score ranges from 0 to 9, with lower scores meaning fewer symptoms and better disease control, and higher scores meaning more severe disease activity.

A score of 2.5 or below suggests the disease is in remission.

Corticosteroid-free Clinical Remission (Partial Mayo Score) is defined as:

• Meeting the criteria for clinical remission by Partial Mayo Score <=2.5, and
• No use of oral systemic corticosteroids in the prior 90 days.

The Partial Mayo Score is a tool that helps doctors measure ulcerative colitis activity without endoscopy. It combines three components:

• Stool Frequency (SF) subscore: range 0-3 (higher score = more frequent stools)
• Rectal Bleeding (RB) subscore: range 0-3 (higher score = more bleeding)
• Physician's Global Assessment (PGA): range 0-3 (higher score = worse overall condition based on physician's judgment)

The total score ranges from 0 to 9, with lower scores meaning fewer symptoms and better disease control, and higher scores meaning more severe disease activity

Clinical Response by Partial Mayo Score is defined as:

• Decrease in partial Mayo score ⩾ 2 points and ⩾ 30% from baseline, and
• Decrease in rectal bleeding subscore > 1 point or absolute rectal bleeding score < 1 This represents a marked improvement in disease activity.

The Partial Mayo Score is a tool that helps doctors measure ulcerative colitis activity without endoscopy. It combines three components:

• Stool Frequency (SF) subscore: range 0-3 (higher score = more frequent stools)
• Rectal Bleeding (RB) subscore: range 0-3 (higher score = more bleeding)
• Physician's Global Assessment (PGA): range 0-3 (higher score = worse overall condition based on physician's judgment)

The total score ranges from 0 to 9, with lower scores meaning fewer symptoms and better disease control, and higher scores meaning more severe disease activity.

Clinical remission by Modified Mayo Score is defined as meeting all of the following criteria:

• Stool Frequency (SF) subscore ≤ 1, with at least a 1-point decrease from baseline
• Rectal Bleeding (RB) subscore = 0
• Endoscopic Subscore (ES) ≤ 1

The Modified Mayo Score is the sum of the following components (Range: 0-9):

• SF subscore: range 0-3 (higher score = more frequent stools)
• RB subscore: range 0-3 (higher score = more bleeding)
• ES: range 0-3 (higher score = more severe inflammation seen during endoscopy)

The total score ranges from 0 to 9, with lower scores meaning less disease activity and better clinical condition, and higher scores meaning more severe disease activity.

Endoscopic Response is defined as:

• A decrease from baseline of ≥ 1 point in the Mayo Endoscopic Score (ES).

Mayo Endoscopic Score: range 0-3

• Higher ES scores = more severe inflammation and worse mucosal appearance
• Lower ES scores = less inflammation and better mucosal healing

Endoscopic Improvement is defined as:

• Mayo Endoscopic Score (ES) ≤ 1

Mayo Endoscopic Score (ES): range 0-3

• Higher ES scores = more severe inflammation and worse mucosal appearance
• Lower ES scores = less inflammation and better mucosal healing

Histological Improvement is defined as:

• Achieving a Geboes score < 3.1

The Geboes score is a grading system used to assess inflammation in tissue samples under a microscope.

• Each domain is graded on a scale, and the total score ranges from 0 to 5.4, with higher scores indicating more severe histologic disease activity.
• Higher Geboes scores = more severe microscopic inflammation
• Lower Geboes scores = less inflammation and better healing

IBDQ is a tool to assess patient experience in inflammatory bowel diseases (Ulcerative Colitis [UC] and Crohn's Disease [CD]).

It includes 32 questions across 4 dimensions:

• Bowel symptoms (10 items)
• Systemic symptoms (5 items)
• Emotional function (12 items)
• Social function (5 items)

Scoring: Each question ranges from 1 ("worst") to 7 ("best"). Total score: 32-224, with higher scores indicating better quality of life (QOL).

An increase from baseline reflects improved health-related quality of life (HRQOL). The IBDQ is used in registrational studies to evaluate bowel symptoms, functional abdominal symptoms, and overall HRQOL.

IBDQ is a tool to assess patient experience in inflammatory bowel diseases (Ulcerative Colitis [UC] and Crohn's Disease [CD]).

It includes 32 questions across 4 dimensions:

• Bowel symptoms: 10 items
• Systemic symptoms: 5 items
• Emotional function: 12 items
• Social function: 5 items

Scoring:

• Each question ranges from 1 ("worst") to 7 ("best").
• Total score: 32-224, with higher scores indicating better quality of life (QOL).

A change from baseline in total score of ≥16 points reflect meaningful IBDQ response. The IBDQ is used in registrational studies to evaluate bowel symptoms, functional abdominal symptoms, and overall health-related quality of life (HRQOL).

IBDQ is a tool to assess patient experience in inflammatory bowel diseases (Ulcerative Colitis [UC] and Crohn's Disease [CD]).

It includes 32 questions across 4 dimensions:

• Bowel symptoms: 10 items
• Systemic symptoms: 5 items
• Emotional function: 12 items
• Social function: 5 items

Scoring:

• Each question ranges from 1 ("worst") to 7 ("best").
• Total score: 32-224, with higher scores indicating better quality of life (QOL).

A total score of ≥170 points reflects IBDQ remission, meaning the participant reports very few symptoms and good overall quality of life. The IBDQ is used in registrational studies to evaluate bowel symptoms, functional abdominal symptoms, and overall health-related quality of life (HRQOL).

Clinical remission by Modified Mayo Score is defined as meeting all of the following criteria:

• Stool Frequency (SF) subscore ≤ 1, with at least a 1-point decrease from baseline
• Rectal Bleeding (RB) subscore = 0
• Endoscopic Subscore (ES) ≤ 1

The Modified Mayo Score is the sum of the following components (Range: 0-9):

• SF subscore: range 0-3 (higher score = more frequent stools)
• RB subscore: range 0-3 (higher score = more bleeding)
• ES: range 0-3 (higher score = more severe inflammation seen during endoscopy)

The total score ranges from 0 to 9, with lower scores meaning less disease activity and better clinical condition, and higher scores meaning more severe disease activity.

Endoscopic Response is defined as:

• A decrease from baseline of ≥ 1 point in the Mayo Endoscopic Sub score (ES).

This represents the percentage of treated participants who achieved a decrease from baseline of at least 1 point in the Mayo ES, indicating improvement in mucosal appearance during endoscopy.

Mayo Endoscopic Subscore (ES): range 0-3

• Higher ES scores = more severe inflammation and worse mucosal appearance
• Lower ES scores = less inflammation and better mucosal healing

Endoscopic Improvement is defined as:

• Mayo Endoscopic Subscore (ES) ≤ 1

This represents the percentage of treated participants with Mayo ES ≤ 1, indicating mild or no inflammation.

Mayo Endoscopic Subscore (ES): range 0-3

• Higher ES scores = more severe inflammation and worse mucosal appearance
• Lower ES scores = less inflammation and better mucosal healing

Endoscopic Remission is defined as:

• Mayo Endoscopic Sub score (ES) = 0

This represents the percentage of treated participants with Mayo ES = 0, indicating complete mucosal healing.

Mayo Endoscopic Sub score (ES): range 0-3

• Higher ES scores = more severe inflammation and worse mucosal appearance
• Lower ES scores = less inflammation and better mucosal healing

Histological Improvement is defined as:

• Achieving a Geboes score < 3.1

The Geboes score is a grading system used to assess inflammation in tissue samples under a microscope.

• Each domain is graded on a scale, and the total score ranges from 0 to 5.4, with higher scores indicating more severe histologic disease activity.
• Higher Geboes scores = more severe microscopic inflammation
• Lower Geboes scores = less inflammation and better healing

Histological Remission is defined as:

• Achieving a Geboes score < 2

The Geboes score is a grading system used to assess inflammation in tissue samples under a microscope.

• Each domain is graded on a scale, and the total score ranges from 0 to 5.4, with higher scores indicating more severe histologic disease activity.
• Higher Geboes scores = more severe microscopic inflammation
• Lower Geboes scores = minimal or no inflammation and better healing

IBDQ is a tool to assess patient experience in inflammatory bowel diseases (Ulcerative Colitis [UC] and Crohn's Disease [CD]).

It includes 32 questions across 4 dimensions:

• Bowel symptoms (10 items)
• Systemic symptoms (5 items)
• Emotional function (12 items)
• Social function (5 items)

Scoring: Each question ranges from 1 ("worst") to 7 ("best"). Total score: 32-224, with higher scores indicating better quality of life (QOL).

An increase from baseline reflects improved health-related quality of life (HRQOL). The IBDQ is used in registrational studies to evaluate bowel symptoms, functional abdominal symptoms, and overall HRQOL.

IBDQ is a tool to assess patient experience in inflammatory bowel diseases (Ulcerative Colitis [UC] and Crohn's Disease [CD]).

It includes 32 questions across 4 dimensions:

• Bowel symptoms: 10 items
• Systemic symptoms: 5 items
• Emotional function: 12 items
• Social function: 5 items

Scoring:

• Each question ranges from 1 ("worst") to 7 ("best").
• Total score: 32-224, with higher scores indicating better quality of life (QOL).

A change from baseline in total score of ≥16 points reflect meaningful IBDQ response. The IBDQ is used in registrational studies to evaluate bowel symptoms, functional abdominal symptoms, and overall health-related quality of life (HRQOL).

IBDQ is a tool to assess patient experience in inflammatory bowel diseases (Ulcerative Colitis [UC] and Crohn's Disease [CD]).

It includes 32 questions across 4 dimensions:

• Bowel symptoms: 10 items
• Systemic symptoms: 5 items
• Emotional function: 12 items
• Social function: 5 items

Scoring:

• Each question ranges from 1 ("worst") to 7 ("best").
• Total score: 32-224, with higher scores indicating better quality of life (QOL).

A total score of ≥170 points reflect IBDQ remission, meaning the participant reports very few symptoms and good overall quality of life. The IBDQ is used in registrational studies to evaluate bowel symptoms, functional abdominal symptoms, and overall health-related quality of life (HRQOL).

Corticosteroid-free Clinical Remission (modified mayo score) is defined as:

• Meeting the criteria for clinical remission by Modified Mayo Score [Stool Frequency (SF) subscore ≤ 1, with ≥ 1 point decrease from baseline and; Rectal Bleeding (RB) subscore = 0 and; Endoscopic Subscore (ES) ≤ 1], and
• No oral systemic steroid use in the prior 90 days.

The Modified Mayo Score is the sum of the following components (Range: 0-9):

• Stool Frequency (SF) subscore: range 0-3 (higher score = more frequent stools)
• Rectal Bleeding (RB) subscore: range 0-3 (higher score = more bleeding)
• Endoscopic Subscore (ES): range 0-3 (higher score = more severe inflammation seen during endoscopy)

The total score ranges from 0 to 9, with:

• Lower scores = less disease activity and better clinical condition
• Higher scores = more severe disease activity

Histo-endoscopic Mucosal Improvement (HEMI) is defined as:

• Mayo Endoscopic Subscore (ES) ≤ 1, and
• Geboes score < 3.1

Mayo Endoscopic Subscore (ES): range 0-3

• Higher ES scores = more severe visible inflammation and worse mucosal appearance
• Lower ES scores = less visible inflammation and better mucosal healing

Geboes Score:

• Each domain is graded on a scale, and the total score ranges from 0 to 5.4, with higher scores indicating more severe histologic disease activity
• Higher Geboes scores = more severe microscopic inflammation
• Lower Geboes scores = less microscopic inflammation and better tissue healing

Meeting both criteria (ES ≤ 1 and Geboes < 3.1) shows improvement in both endoscopic appearance and microscopic tissue health.