A Study of Abatacept in Patients With Active Ulcerative Colitis

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore ≤ 1 point

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point.

The Inflammatory Bowel Disease Questionnaire (IBDQ) was used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. The response to each question can range from 1 to 7, with 1 indicating severe problem and 7 indicating normal health. The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score can range between 32 to 224 with higher scores indicating a better quality of life.

The Inflammatory Bowel Disease Questionnaire (IBDQ) was used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. The response to each question can range from 1 to 7, with 1 indicating severe problem and 7 indicating normal health. The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score can range between 32 to 224 with higher scores indicating a better quality of life.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute rectal bleeding subscore of ≤1 point was indicative of mild disease.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute stool frequency subscore of ≤1 point was indicative of mild disease.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute PGA subscore of ≤1 point was indicative of mild disease.

The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical response=reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point. Inadequate response/intolerance=inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.

The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical response=reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point. Inadequate response/intolerance=inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.

The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point. Inadequate response/intolerance

=inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore ≤ 1 point. Inadequate response/intolerance = inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).

Complete physical examination was obtained at the Screening Visit, Day MP-365, and OL Final Visit/Early Termination visits. Interim physical examinations were performed at other study visits. Interim physical exam were not as comprehensive as the initial full examination but did note any changes in the participant's condition since the last assessment and did not preclude examination of any of the body systems as clinically indicated. Participants were observed for AEs and vital signs (blood pressure, heart rate, and temperature).

High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL.

Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): >2 x ULN; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; Sodium (Na): <0.95 x LLN/ >1.05 x ULN; potassium (K): <0.9 x LLN/ >1.1 x ULN; calcium (Ca): <0.8 x LLN/>1.2 x ULN; phosphorous (P): <0.75 x LLN/ >1.2 5 x ULN

Low=lower than LLN, High=greater than ULN. LLN/ULN= serum glucose (Glu): <65 mg/dL/ >220 mg/dL; total protein: < 0.9 x LLN/ >1.1 x ULN; albumin:<0.9 x LLN; uric acid: >1.5 x ULN. For Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, Red Blood Cells [RBCs], White Blood Cells [WBCs]): Use ≥2 when BL value missing or value ≥4, or when pre-dose=0 or 0.5. Use ≥3 when pre-dose=1. Use ≥4 when pre-dose=2 or 3

High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; eosinophils: >0.750 x 10^3 c/uL; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; Sodium (Na): <0.95 x LLN/ >1.05 x ULN; potassium (K): <0.9 x LLN/ >1.1 x ULN; phosphorous (P): <0.75 x LLN/ >1.2 5 x ULN;

Low=lower than LLN, High=greater than ULN. LLN/ULN= serum glucose (Glu): <65 mg/dL/ >220 mg/dL; total protein: < 0.9 x LLN/ >1.1 x ULN; albumin:<0.9 x LLN. For Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, Red Blood Cells [RBCs], White Blood Cells [WBCs]): Use ≥2 when BL value missing or value ≥4, or when pre-dose=0 or 0.5. Use ≥3 when pre-dose=1. Use ≥4 when pre-dose=2 or 3

A electrochemiluminescent immunoassay screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-Abatacept reactivity. CTLA4 and Possibly Ig category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore ≤ 1 point

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point.

Baseline corticosteroids equivalent of ≤30 mg prednisone daily. The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater frequency or severity. Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point.

The Inflammatory Bowel Disease Questionnaire (IBDQ) was used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. The response to each question can range from 1 to 7, with 1 indicating severe problem and 7 indicating normal health. The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score can range between 32 to 224 with higher scores indicating a better quality of life.

The SF-36 is a validated instrument to measure health-related quality of life across multiple disease states. Individual subscale scores and 2 summary scores are calculated: (1) physical component summary (PCS) which includes physical functioning, role-physical, bodily pain, and general health; (2) mental component summary (MCS) which includes vitality, social functioning, role-emotional, and mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight, with values ranging from worse health (0) to best health (100).

Baseline corticosteroids equivalent of ≤30 mg prednisone daily. The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater frequency or severity. Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute rectal bleeding subscore of ≤1 point was indicative of mild disease.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute stool frequency subscore of ≤1 point was indicative of mild disease.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute PGA subscore of ≤1 point was indicative of mild disease.

The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical response=reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point. Inadequate response/intolerance=inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.

The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point. Inadequate response/intolerance =inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore ≤1 point. Inadequate response/intolerance = inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.

A electrochemiluminescent immunoassay screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-Abatacept reactivity. CTLA4 and Possibly Ig category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.

AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).

Complete physical examination was obtained at the Screening Visit, Day MP-365, and OL Final Visit/Early Termination visits. Interim physical examinations were performed at other study visits. Interim physical exam were not as comprehensive as the initial full examination but did note any changes in the participant's condition since the last assessment and did not preclude examination of any of the body systems as clinically indicated. Participants were observed for AEs and vital signs (blood pressure, heart rate, and temperature).

High=greater than ULN, Low=lower than LLN. LLN/ULN= HGB: >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; PLT: <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL; GGT: >2 x ULN; Bilirubin: >2 x ULN; BUN: >2 x BL; Na: <0.95 x LLN/ >1.05 x ULN; K: <0.9 x LLN/ >1.1 x ULN; Ca: <0.8 x LLN/>1.2 x ULN

Low=lower than LLN, High=greater than ULN. LLN/ULN= serum glucose (Glu): <65 mg/dL/ >220 mg/dL; fasting serum Glu: <0.8 x LLN/ >1.5 x ULN; total protein: < 0.9 x LLN/ >1.1 x ULN; albumin:<0.9 x LLN; uric acid: >1.5 x ULN. For Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, Red Blood Cells [RBCs], White Blood Cells [WBCs]): Use ≥2 when BL value missing or value ≥4, or when pre-dose=0 or 0.5. Use ≥3 when pre-dose=1. Use ≥4 when pre-dose=2 or 3

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point.

The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore ≤ 1 point

The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical response=reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point. Clinical remission = Mayo score of ≤ 2 points with no individual subscore exceeding 1 point. Change from Baseline= post-Baseline - Baseline value.

A electrochemiluminescent immunoassay screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-Abatacept reactivity. CTLA4 and Possibly Ig category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.

Participants taking oral corticosteroids (equivalent of ≤ 30 mg prednisone daily) must have met minimum treatment duration at entry into IP and had stable dose for ≥2 weeks prior to entry into the IP.