A Study of Ustekinumab in Pediatric Participants With Moderately to Severely Active Ulcerative Colitis (UC)

Clinical response was defined as a decrease from induction baseline in the Modified Mayo score by >=30 percent (%) and >= 2 points, with either a decrease from baseline in the rectal bleeding subscore >=1 or a rectal bleeding subscore of 0 or 1. The modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review, each subscore graded from 0 (normal) to 3 (severe) with higher scores indicating more severe disease. These individual subscores were summed up to give a total modified Mayo score range of 0 (normal) to 9 (severe disease), where higher scores indicated more severe disease activity. Baseline was defined as the last observation prior to or at the time of the first study intervention.

Symptomatic remission was defined as a Mayo stool frequency subscore of 0 (normal number of stools) or 1 (1-2 stools more than normal) and a rectal bleeding subscore of 0 (no blood seen), where the stool frequency subscore had not increased from induction baseline. The modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review, each subscore graded from 0 (normal) to 3 (severe) with higher scores indicating more severe disease. These individual subscores were summed up to give a total modified Mayo score range of 0 (normal) to 9 (severe disease), where higher scores indicated more severe disease activity. Baseline was defined as the last observation prior to or at the time of the first study intervention.

Percentage of participants with clinical remission at Induction Week 8 as assessed by PUCAI score was reported. Clinical remission as measured by the PUCAI score was a PUCAI score <10. PUCAI score was intended for pediatric participants with UC. PUCAI consisted of the following 6 subscores with scores as: abdominal pain (no pain =0, pain can be ignored =5, pain cannot be ignored =10); rectal bleeding (none =0, small amount only [in less than 50 % of stools] =10, small amount with most stools =20, large amount [>50% of the stool content] =30); stool consistency of most stools (formed =0, partially formed =5, completely unformed =10); number =0, occasional limitation of activity =5, severely restricted activity =10). PUCAI total score ranges from 0 to 85, with higher scores indicating greater disease severity.

Endoscopic improvement was defined as a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy. The modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review, each subscore graded from 0 (normal) to 3 (severe) with higher scores indicating more severe disease. These individual subscores were summed up to give a total modified Mayo score range of 0 (normal) to 9 (severe disease), where higher scores indicated more severe disease activity.

Histologic-endoscopic mucosal improvement based on Geboes score (GS) was defined as achieving a combination of histologic improvement (neutrophil infiltration in <5% of crypts, no crypt destruction, no erosions, ulcerations or granulation tissue according to Geboes grading system) and endoscopic improvement (Mayo subscore of 0 or 1 with no friability in endoscopy). GS has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils, eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; and Grade 5, erosions or ulceration. Higher score, more severe disease. Modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore determined during central review, each subscore graded from 0 (normal) to 3 (severe). Individual subscores were summed up to give total modified Mayo score range of 0 (normal) to 9 (severe disease), higher score=more severe disease.

Clinical remission was defined by Mayo subscores as: a stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline. Mayo score consists of 4 subscores (stool frequency, rectal bleeding, endoscopy findings, and physician's global assessment), rated as 0 (normal) to 3 (severe). Total score was calculated as the sum of 4 subscores and range from 0 to 12, where 3 to 5= mild; 6 to 10= moderate; and 11 to 12= severe; higher scores indicate worsening of disease. Baseline was defined as the last observation prior to or at the time of the first study intervention.

Symptomatic remission was defined as a Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0, where the stool frequency subscore has not increased from induction baseline. The modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review, each subscore graded from 0 (normal) to 3 (severe) with higher scores indicating more severe disease. These individual subscores were summed up to give a total modified Mayo score range of 0 (normal) to 9 (severe disease), where higher scores indicated more severe disease activity. Baseline was defined as the last observation prior to or at the time of the first study intervention.

Percentage of participants with clinical remission at Maintenance Week 44 as assessed by PUCAI score was reported. Clinical remission as measured by the PUCAI score was a PUCAI score <10. PUCAI score was intended for pediatric participants with UC. PUCAI consisted of the following 6 subscores with scores as: abdominal pain (no pain =0, pain can be ignored =5, pain cannot be ignored =10); rectal bleeding (none =0, small amount only [in less than 50% of stools] =10, small amount with most stools =20, large amount [>50% of the stool content] =30); stool consistency of most stools (formed =0, partially formed =5, completely unformed =10); number of stools per 24 hours (0-2 =0, 3-5 =5, 6-8 =10, >8 =15); nocturnal bowel movement (no =0, yes =10); activity level (no limitation of activity =0, occasional limitation of activity =5, severely restricted activity =10). PUCAI total score ranges from 0 to 85, with higher scores indicating greater disease severity.

Endoscopic improvement was defined as a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy. Modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review, each subscore graded from 0 (normal) to 3 (severe). These individual subscores were summed up to give a total modified Mayo score range of 0 (normal) to 9 (severe disease), higher scores indicated more severe disease.

Corticosteroid-free clinical remission was defined as a Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline; and not receiving corticosteroids for at least 90 days prior to Week M-44. The modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review, each subscore graded from 0 (normal) to 3 (severe) with higher scores indicating more severe disease. These individual subscores were summed up to give a total modified Mayo score range of 0 (normal) to 9 (severe disease), where higher scores indicated more severe disease activity. Baseline was defined as the last observation prior to or at the time of the first study intervention.

Corticosteroid-free clinical remission was defined as a Mayo stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline; and not receiving corticosteroids for at least 90 days prior to Week M-44. The modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review, each subscore graded from 0 (normal) to 3 (severe) with higher scores indicating more severe disease. These individual subscores were summed up to give a total modified Mayo score range of 0 (normal) to 9 (severe disease), where higher scores indicated more severe disease activity. Baseline was defined as the last observation prior to or at the time of the first study intervention.

Clinical remission was defined by Mayo subscores as: a stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1 with no friability present on the endoscopy, where the stool frequency subscore has not increased from induction baseline. The modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore as determined during central review, each subscore graded from 0 (normal) to 3 (severe) with higher scores indicating more severe disease. These individual subscores were summed up to give a total modified Mayo score range of 0 (normal) to 9 (severe disease), where higher scores indicated more severe disease activity. Baseline was defined as the last observation prior to or at the time of the first study intervention.

Histologic-endoscopic mucosal improvement based on Geboes Score: achieving a combination of histologic improvement (neutrophil infiltration in <5% of crypts, no crypt destruction, no erosions, ulcerations or granulation tissue according to Geboes grading system), endoscopic improvement (Mayo sub-score of 0 or 1 with no friability in endoscopy). GS has 6 grades, each with 3-5 subgrades: Grade 0, structural change only; Grade 1, chronic inflammation; Grade 2, lamina propria neutrophils, eosinophils; Grade 3, neutrophils in epithelium; Grade 4, crypt destruction; Grade 5, erosions or ulceration. Higher score indicated more severe disease. Modified Mayo scores consisted of 3 subscores: stool frequency, rectal bleeding, endoscopic subscore as determined during central review, each subscore graded from 0 (normal) to 3 (severe). These individual subscores were summed up to give total modified Mayo score range of 0 (normal) to 9 (severe disease), higher scores indicated more severe disease.