A Study of Tofacitinib in Patients With Ulcerative Colitis in Stable Remission

Time to loss of remission(flare): time from first drug administration until time of meeting loss of remission criteria based on modified mayo score. Loss of remission: meeting at least (>=)1 criteria: increase from Baseline in rectal bleeding subscore by >=1 point and increase in endoscopic subscore by >=1 point; increase from Baseline in rectal bleeding subscore by >=2 points and endoscopic subscore >0; increase in stool frequency subscore by >=2 points and increase in endoscopic subscore by >=1 point; increase in endoscopic subscore by >=2 points. Modified mayo score included 3 components: stool frequency, rectal bleeding and endoscopic subscores: Modified mayo score included 3 components: stool frequency, rectal bleeding and endoscopic subscores, each subscore graded from 0 to 3 with higher scores for each score=more severe disease. All scores summed up to give total modified mayo score range from 0 to 9; higher scores=more severe disease.

Remission as per modified partial mayo score was defined as stool frequency subscore of 0 or 1, and rectal bleeding sub score of 0 at the specified time points. Modified partial mayo scores consisted of 2 components: stool frequency and rectal bleeding: each subscore graded from 0 to 3 with higher scores for each score = more severe disease. These scores were summed up to give a total modified partial mayo score range of 0 to 6; where higher scores indicating more severe disease.

Remission as per total mayo score was defined by a total mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and physician global assessment (PGA), each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total mayo score range of 0 to 12, where higher scores indicating more severe disease.

Remission as per partial mayo score was defined as partial mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. Partial mayo score was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 subscores: stool frequency, rectal bleeding and PGA with each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total partial mayo score range from 0 (normal or inactive disease) to 9 (severe disease) with higher scores indicating more severe disease.

Remission as per modified mayo score was defined as an endoscopic subscore of 0 or 1, stool frequency subscore of 0 or 1, and rectal bleeding subscore of 0. Modified mayo score consisted of 3 components: stool frequency subscore, rectal bleeding subscore and endoscopic subscore: higher scores for each score = more severe disease. These scores were summed up to give a total modified mayo score range of 0 to 9; where higher scores indicating more severe disease.

Modified mayo score is an instrument designed to measure disease activity of UC. Modified mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore, each subscore graded from 0 to 3 with higher scores indicating more severe disease. These individual scores were summed up to give a total modified mayo score range of 0 to 9, where higher scores indicated more severe disease.

Modified mayo score is an instrument designed to measure disease activity of UC. Modified mayo scores consisted of 3 subscores: stool frequency, rectal bleeding and endoscopic subscore, each subscore graded from 0 to 3 with higher scores indicating more severe disease. These individual scores were summed up to give a total modified mayo score range of 0 to 9, where higher scores indicated more severe disease.

Modified partial mayo scores consisted of 2 subscores: stool frequency and rectal bleeding with each subscore graded from 0 to 3 with higher scores indicating more severe disease. Individual subscores were summed up to give a total Modified partial mayo score ranges from 0 (normal or inactive disease) to 6 (severe disease) with higher scores indicating more severe disease.

Modified partial mayo scores consisted of 2 subscores: stool frequency and rectal bleeding with each subscore graded from 0 to 3 with higher scores indicating more severe disease. Individual subscores were summed up to give a total modified partial mayo score range from 0 (normal or inactive disease) to 6 (severe disease) with higher scores indicating more severe disease.

Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total mayo score range of 0 to 12, where higher scores indicating more severe disease.

Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total mayo score range of 0 to 12, where higher scores indicating more severe disease.

Partial mayo score was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 subscores: stool frequency, rectal bleeding and PGA with each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total partial mayo score range from 0 (normal or inactive disease) to 9 (severe disease) with higher scores indicating more severe disease.

Partial mayo score was an instrument designed to measure disease activity of UC without endoscopy. It consisted of 3 subscores: stool frequency, rectal bleeding and PGA with each subscore graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a total partial mayo score ranges from 0 (normal or inactive disease) to 9 (severe disease) with higher scores indicating more severe disease.

Mucosal healing in participants was defined as the mayo endoscopic subscore of 0 or 1. The Mayo endoscopic subscore consisted of the findings of centrally read flexible sigmoidoscopy, graded from 0 to 3 with higher scores indicated more severe disease.

Clinical response was defined as a decrease from baseline in mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Mayo score is an instrument designed to measure disease activity of UC. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible sigmoidoscopy and PGA, each sub score graded from 0 to 3 with higher scores indicating more severe disease. PGA included 3 criteria: participant's recollection of abdominal discomfort, general sense of wellbeing and other observations such as physical findings and performance status. Individual subscores were summed up to give a mayo score range of 0 to 12, where higher scores indicating more severe disease.

Change from baseline in fecal calprotectin (in micrograms per gram [mcg/g]) was reported.

Change From baseline in hs-CRP level (in milligrams per liter [mg/L]) is reported.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs included both serious and all non-serious adverse events (irrespective of frequency threshold used to report other AEs in safety section).

Serious infections were defined as any infections (viral, bacterial, and fungal) requiring parenteral antimicrobial therapy, hospitalization for treatment, or meeting other criteria that require the infection to be classified as serious adverse event. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events.

Abnormality criteria: Hematology: hemoglobin(Hg): <0.8* lower limit of normal (LLN); hematocrit: <0.8*LLN; lymphocytes: <0.8* LLN; lymphocytes/leukocytes: <0.8*LLN; erythrocytes: <0.8*LLN; erythrocytes mean corpuscular volume: <0.9*LLN; erythrocytes mean corpuscular Hg: <0.9*LLN; reticulocytes, reticulocytes/erythrocytes:>1.5* upper limit of normal (ULN); neutrophils, neutrophils/leukocytes: >1.2*ULN; basophils/leukocytes, eosinophils, eosinophils/leukocytes, monocytes/leukocytes: >1.2*ULN; leukocyte esterase: >=1; Clinical chemistry: bicarbonate:<0.9*LLN, bilirubin: >1.5*ULN; indirect bilirubin: >1.5* ULN; aspartate aminotransferase(AT): >3.0*ULN; alanine AT: >3.0*ULN; gamma glutamyl transferase: >3.0* ULN; creatine kinase: >2.0*ULN; potassium: >1.1*ULN; blood urea nitrogen: >1.3*ULN; creatinine: >1.3*ULN; urate: >1.2*ULN; cholesterol: >1.3*ULN; HDL-cholesterol: <0.8* LLN; LDL-cholesterol: >1.2*ULN; triglycerides: >1.3*ULN; glucose: >1.5*ULN; and urine Hg >=1.

Laboratory abnormalities leading to study treatment discontinuation: 2 sequential neutrophil counts <750 neutrophils per cubic millimeter (mm^3); 2 sequential lymphocyte counts <500 lymphocytes/mm^3; 2 sequential hemoglobin <8.0 grams per deciliter; 2 sequential platelet counts <75000 platelets/mm^3; 2 sequential AST or ALT elevations >=3*ULN with at least one total bilirubin value >=2*ULN; 2 sequential AST or ALT elevations >=3*ULN accompanied by signs or symptoms consistent with hepatic injury; 2 sequential AST or ALT elevations >=5*ULN; 2 sequential increases in creatinine >50% and >0.5 milligrams per deciliter over A3921139 baseline; 2 sequential CK elevations >10*ULN unless the causality is known not to be medically serious (eg, exercise induced).

Vital signs abnormality criteria included: 1) a) diastolic blood pressure (DBP) of (less than) <50 millimeter of mercury (mmHg), b) change greater than equal to (>=) 20 mmHg increase, c) change >=20 mmHg decrease; 2) a) systolic blood pressure (SBP) of <90 mmHg, b) change >=30 mmHg increase, c) change >=30 mmHg decrease; 3) a) pulse rate value of <40 beats per minute (bpm), b) pulse rate >120 bpm. Only those categories in which at least 1 participant had data were reported.

Physical examination included assessment of the weight, general appearance, eyes, mouth, lungs, heart, abdomen, musculoskeletal, extremities, skin and lymph nodes. Clinical significance was assessed by the Investigator.

Number of participants with adjudicated opportunistic infections including herpes zoster (non-adjacent or >2 adjacent dermatomes); all malignancies including non-melanoma skin cancer; gastrointestinal perforation and cardiovascular events including pulmonary embolism and cerebrovascular accident, adjudicated by adjudication committee were reported.