CP-690, 550

According to PRCSG/PRINTO, disease flare defined as worsening of \>=30 percent(%) in \>=3 of 6 variables of JIA core set, with no more than 1 variable improving by \>=30%. Six core variables: 1) Number of joints with active arthritis (joint with swelling/in absence of swelling, limited range of motion accompanied by pain/tenderness), 2)Number of joints with limited range of motion, 3) Physician global evaluation of disease activity (assessed on a Visual Analog Scale\[VAS\] of 0\[no activity\] to 10\[maximum activity\]), 4) Parent/legal guardian/participant global assessment of overall well-being (assessed on VAS of 0\[very well\] to 10\[very poor\], 5) Childhood Health Assessment Questionnaire- Disability Index (CHAQ-DI): 30 questions in 8 domains, each question answered on scale of 0=without difficulty to 3=unable to do; scores of each domain were averaged to derive total CHAQ-DI score,which ranges from 0 (minimum dysfunction) to 3 (most severe dysfunction);6) Erythrocyte Sedimentation Rate(ESR).

The PGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 5-point severity scale (0 \[no symptom\] to 4 \[severe symptom\]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and category (0=clear; 1=almost clear; 2=mild; 3=moderate; and 4=severe). PGA response was defined as 0 (clear) or 1 (almost clear).

The PASI quantifies the severity of a participant's psoriasis based on both "lesion severity" and the "percent of body surface area (BSA)" affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\], and lower limbs \[including buttocks\]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI75 response was defined as at least a 75% reduction in PASI relative to Baseline.

An AE was any untoward medical occurrence in a participant who received study drug 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. Treatment-emergent were events between first dose of study drug and up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and all non-serious AEs.

Serious infections were treated infections that required parenteral antimicrobial therapy or hospitalization for treatment or; met other criteria that required the infection to be classified as a serious adverse event (SAE). 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. Treatment-emergent were events between first dose of study drug and up to 81 months for Tofacitinib 5 mg BID group and up to 85 months for Tofacitinib 10 mg BID group that were absent before treatment or that worsened relative to pretreatment state.

Laboratory abnormalities: Hemoglobin, hematocrit, RBC: \<0.8\* LLN; reticulocytes (absolute \[Abs\], %): \<0.5\* LLN, \>1.5\* ULN; MCV, MCH: \<0.9\* LLN, \>1.1\* ULN; platelets:\<0.5\* LLN, \>1.75\* ULN; WBC:\<0.6\* LLN,\>1.5\* ULN; lymphocytes (Abs, %), total neutrophils (Abs,%):\<0.8\* LLN, \>1.2\* ULN; Basophils (Abs,%),eosinophils(Abs, %),monocytes(Abs, %):\>1.2\* ULN; total bilirubin,direct bilirubin,indirect bilirubin:\>1.5\* ULN; AST,ALT,gamma GT, LDH,ALP: \>3.0\* ULN; total protein,albumin: \<0.8\* LLN,\>1.2\* ULN: BUN,creatinine: \>1.3\* ULN;uric acid:\>1.2\* ULN; cholesterol,triglycerides: \>1.3\* ULN; cholesterol (HDL: \<0.8\* LLN; LDL: \>1.2\* ULN); sodium: \<0.95\* LLN, \>1.05\* ULN; potassium, chloride, calcium, bicarbonate: \<0.9\* LLN, \>1.1\* ULN; glucose: \<0.6\* LLN; creatine kinase \>2.0\* ULN; urine specific gravity: \<1.003; urine pH: \<4.5; urine (glucose,protein,blood,nitrite,leukocyte,esterase): \>=1; Urine (RBC,WBC): \>=20; urine epithelial cells:\>=6; urine (casts,granular casts,hyaline casts): \>1; urine bacteria:\>20.

Vital sign abnormalities included greater than or equal to (\>=) 30 millimeter of mercury \[mmHg\] increase in systolic blood pressure (BP), \>=30 mmHg decrease in systolic BP, Systolic BP (less than \[\<\] 90 mmHg), \>=20 mmHg increase in diastolic BP, \>=20 mmHg decrease in diastolic BP, diastolic BP (\<50 mmHg), pulse rate (\<40 beats per minute \[BPM\]), pulse rate (greater than \[\>\] 120 BPM).

Physical examinations included weight, general appearance, head, ears, eyes, nose, mouth, throat, thyroid, skin (presence of rash), lungs (auscultation), heart (auscultation for presence of murmurs, gallops, rubs, peripheral edema), abdominal (palpation and auscultation), perianal, musculoskeletal, extremities, neurologic (mental status, gait, reflexes, motor and sensory function, coordination) and lymph nodes. Clinically significant changes were judged by the investigator.

ECG abnormalities criteria: maximum PR interval (\>=300 millisecond); maximum QRS complex (\>=200 millisecond); and maximum QT interval (\>=500 millisecond).

Incidence rates for adjudicated cardiovascular (major adverse cardiovascular event \[MACE\]), malignancy (non-melanoma skin cancer \[NMSC\], malignancies excluding NMSC, opportunistic infections (OIs) (both herpes zoster and non herpes zoster OIs) and thromboembolic (venous thromboembolism) safety events were analyzed. This outcome measure was measured in participants with events per 100 participants-years (pt with events/100 pts-yrs).

Remission in participants 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 was an instrument designed to measure disease activity of ulcerative colitis (UC). It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible sigmoidoscopy and physician global assessment (PGA), each subscore graded from 0 to 3 with higher scores indicating higher disease severity. These subscores were summed up to give a total score range of 0 to 12 where higher score indicating higher disease severity.

The PASI quantifies the severity of a participant's psoriasis based on both, "lesion severity" and the "percent of body surface area (BSA)" affected. PASI is a composite scoring assessed by the investigator, of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\], and lower limbs \[including buttocks\]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI75 response was defined as at least a 75 percent (%) reduction in PASI at Week 16 relative to Baseline.

The PGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 5-point severity scale (0 \[no symptom\] to 4 \[severe symptom\]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and category (0=clear; 1=almost clear; 2=mild; 3=moderate; and 4=severe). PGA response was defined as 0 (clear) or 1 (almost clear).

ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in tender joint count; \>=20% improvement in swollen joint count; and \>=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).

Adjudicated cardiovascular events were assessed by investigators as independent reviewers based on event documentation including: hospital discharge summaries, operative reports, clinic notes, ECGs, diagnostic enzymes, results of other diagnostic tests, autopsy reports and death certificate information; specific requirements vary with the event requiring adjudication.

For all biopsies of potentially malignant tumors, suspicious lymphadenopathy, or possible extranodal LPD, the study site requested the pathologist to send the original slides used to make the definitive diagnosis, ancillary study reports, and the pathologist's report to the central laboratory for a blinded review by a central pathologist.

The PGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 5-point severity scale (0 \[no symptom\] to 4 \[severe symptom\]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the PGA score and category (0=clear; 1=almost clear; 2=mild; 3=moderate; and 4=severe). PGA response was defined as 0 (clear) or 1 (almost clear).

The PASI quantifies the severity of a participant's psoriasis based on both, "lesion severity" and the "percent of body surface area (BSA)" affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\], and lower limbs \[including buttocks\]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI 75 response was defined as at least a 75 percent (%) reduction in PASI relative to Baseline.

The PGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 5-point severity scale (0 to 4). The severity scores are summed and averaged after which the total average is rounded to the nearest whole number score to determine the PGA score and category (0=clear; 1=almost clear; 2=mild; 3=moderate; and 4=severe). PGA response was defined as 0 (clear) or 1 (almost clear).

The PASI quantifies the severity of a participant's psoriasis based on both lesion severity and the percent of body surface area (BSA) affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\], and lower limbs \[including buttocks), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI75 response was defined as at least a 75 percent (%) reduction in PASI relative to baseline/Day 1.

The PASI quantifies the severity of a participant's psoriasis based on both lesion severity and the percent of body surface area (BSA) affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\], and lower limbs \[including buttocks), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI75 response defined as at least a 75 percent (%) reduction in PASI relative to baseline.

The PGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 5-point severity scale (0=clear; 1=almost clear; 2=mild; 3=moderate; and 4=severe). PGA response defined as 0 (clear) or 1 (almost clear).

The PASI quantifies the severity of a participant's psoriasis based on both lesion severity and the percent of BSA affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\], and lower limbs \[including buttocks), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. PASI75 response is defined as at least 75% reduction in PASI relative to Baseline/Day 1. Baseline defined as the last observation up to first dosing date in Period C. PASI responses at each period were relative to Baseline-A, where Baseline-A was defined as the last observation up to first dosing date in Period A.

The PGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 5-point severity scale (0=clear; 1=almost clear; 2=mild; 3=moderate; and 4=severe).

mTSS: sum of erosion and joint space narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores range from 0 (normal) to 448 (worst possible total score).

mTSS: sum of erosion and JSN scores for 44 joints (16 per hand and 6 per foot). mTSS scores range from 0 (normal) to 448 (worst possible total score). An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represents improvement.

ACR70 response: greater than or equal to (≥) 70 percent (%) improvement in tender joints count (TJC) or swollen joints count (SJC) and ≥70% improvement in at least 3 of 5 remaining ACR core measures: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability (disability index of the Health Assessment Questionnaire \[HAQ\]), and 5) C-reactive protein (CRP).

BP: pressure exerted by the blood upon the walls of the blood vessels and especially arteries, usually measured on the radial artery using a sphygmomanometer. Systolic BP: the highest arterial blood pressure of a cardiac cycle occurring immediately after systole of the left ventricle of the heart. Diastolic BP: the lowest arterial blood pressure of a cardiac cycle occurring during diastole of the heart.

BP: pressure exerted by the blood upon the walls of the blood vessels and especially arteries, usually measured on the radial artery using a sphygmomanometer. Systolic BP: the highest arterial blood pressure of a cardiac cycle occurring immediately after systole of the left ventricle of the heart. Diastolic BP: the lowest arterial blood pressure of a cardiac cycle occurring during diastole of the heart.

ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in tender joints count (TJC); \>= 20% improvement in swollen joints count (SJC); and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.

HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities:dress/groom;arise;eat; walk;reach;grip; hygiene;common activities over past week. Each item scored on 4-point scale from 0-3:0=no difficulty;1=some difficulty;2=much difficulty;3=unable to do. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3:0=least difficulty and 3=extreme difficulty. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.

DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, erythrocyte sedimentation rate (ESR)(millimeter/hour \[mm/hour\]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment). Total score range:0-9.4, higher score=more disease activity. DAS28-4 (ESR) less than or equal to (\<=)3.2 implied low disease activity, greater than (\>)3.2 to 5.1 implied moderate to high disease activity, less than (\<)2.6=remission. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.

ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in tender joint count (TJC); \>= 20% improvement in swollen joint count (SJC); and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP). For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.

DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, erythrocyte sedimentation rate (ESR) (millimeters/hour\[mm/hour\]) and patient's global assessment (PtGA) of disease activity(participant rated arthritis activity assessment). Total score range:0-9.4, higher score=more disease activity. DAS28-4 (ESR) less than or equal to (\<=)3.2 implied low disease activity, greater than (\>)3.2 to 5.1 implied moderate to high disease activity, less than (\<)2.6=remission. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.

HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; common activities over past week. Each item scored on 4-point scale from 0-3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as sum of domain scores and divided by number of domains answered. Total possible score range 0-3: 0=least difficulty and 3=extreme difficulty. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.

DAS28-4 (ESR) calculated from SJC and TJC using 28-joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PtGA) of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (\<=) 3.2 implied low disease activity and \> 3.2 to 5.1 implied moderate to high disease activity, and \< 2.6 = remission. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.

mTSS = sum of erosion and Joint Space Narrowing (JSN) scores for 44 joints (16 per hand and 6 per foot). mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change: scores at observation minus score at baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.

DAS28-4 (ESR) calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PtGA) of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range:0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (=\<) 3.2 implied low disease activity, greater than (\>) 3.2 to 5.1 implied moderate to high disease activity and less than (\<) 2.6=remission. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 6 analysis.

DAS28-4 (ESR) calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PtGA) of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range:0 to 9.4, higher score indicated more disease activity. DAS28-4 (ESR) less than or equal to (=\<) 3.2 implied low disease activity, greater than (\>) 3.2 to 5.1 implied moderate to high disease activity and less than (\<) 2.6=remission.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. Treatment-emergent are events between first dose of study drug and up to the last participants visit in the study. The baseline data of Study A3921039, A3921040 or A3921044 were used as baseline data for safety evaluation.

Treatment-emergent non serious AEs by System Organ Class (SOC) (all causalities) and Laboratory Test Abnormalities (without regard to baseline) The stated number of participants analyzed was the total number of participants in each group (AEs). The actual number of participants analyzed for each laboratory parameter varied, and is provided for each. Abs=absolute; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ESR=erythrocyte sedimentation rate; GGT=gamma glutamyl transferase; hgb=hemoglobin; HDL=high density lipids; LDL=low density lipids; LLN=lower limit of normal; qual=qualitative; Tot=total; ULN=upper limit of normal; WBC=white blood cell

An AE was any untoward medical occurrence in a participant who received study drug 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. 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 non-serious adverse events.

Criteria for laboratory abnormalities: hemoglobin (Hg), hematocrit, red blood cell (RBC), high density lipoprotein (HDL) cholesterol:\<0.8\*lower limit of normal (LLN), platelet\<0.5\*LLN/\>1.75\*upper limit of normal (ULN), white blood cell (WBC)\<0.6\*LLN/\>1.5\*ULN, lymphocyte, neutrophil, protein, albumin \<0.8\*LLN/\>1.2\*ULN, basophil, eosinophil, monocyte, low density lipoprotein (LDL) cholesterol: \>1.2\*ULN; bilirubin\>1.5\*ULN, aspartate amino transferase(AT), alanine AT, gammaglutamyl transferase, alkaline phosphatase:\>3.0\*ULN; blood urea nitrogen, creatinine, cholesterol, triglyceride:\>1.3\*ULN; sodium \<0.95\*LLN/\>1.05\*ULN, potassium, chloride, calcium, bicarbonate: \<0.9\*LLN/\>1.1\*ULN; glucose\<0.6\*LLN/\>1.5\*ULN; Urine (specific gravity\<1.003/\>1.030, pH\<4.5/\>8, glucose, ketone, protein, blood/Hg(\>=1; RBC, WBC\>=20; creatinine kinase\>2\*ULN).

Treatment-emergent AEs by SOC (all causalities) - all participants, by time. Data presented for Post Month 96 includes data up to and including Month 114.

Long term safety and tolerability of Tofacitinib was measured as following: percentage (%) of participants with AEs, percentage of participants who discontinued due to AEs. An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.

Pre-specified cardiovascular events were adjudicated by committees of external experts who were blinded to treatment assignment. Potential events of interest (pEoI) were identified by the investigator, sponsor, review of alerts from central electrocardiogram assessments, and by search of adverse events (AE)/serious adverse event (SAE) listings for events coded to death (coronary and non-coronary), myocardial infarction (non-fatal), all coronary revascularization, unstable angina, stroke (fatal and non-fatal), transient ischemic attack, congestive heart failure, peripheral arterial vascular disease, dyspnoea, and chest pain. The independent reviewers (IRs) determined if the pEoI met the criteria for EoI classification according to the definitions summarized from the Clinical Data Interchange Standards Consortium 'Standardized Definitions for End Point Events in Cardiovascular Trials' published October 2010.

Pre-specified malignancy events were adjudicated by committees of external experts who were blinded to treatment assignment. pEoI were identified by the investigator, sponsor, potential primary event notifications (i.e. malignancies excluding non-melanoma skin cancers) for a specific protocol, events submitted for histopathology review for potential malignancies which met the criteria for potential malignancies, and by search of AE/SAE listings for events coded to Malignant tumors Standard Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQ) (20000194). IRs determined if the pEoI met the criteria for EoI classification according to the International Classification of Diseases for Oncology, a ten-digit multi-axial classification of the site (4 characters), morphology (4 digits), behavior (1 digit), and grading (1 digit) of neoplasms.

Pre-specified liver injury events were adjudicated by blinded committees of external experts. pEoI were identified by investigator, sponsor \& search of clinical, safety \& laboratory databases (potential Hy's law event, ALT/AST ≥5 x ULN, events meeting hepatic discontinuation criteria, SAEs coded to MedDRA hepatobiliary system organ class (SOC), AEs/SAEs coded to MedDRA liver infections or infectious biliary disorders SMQ, AEs coded to MedDRA drug-induced liver injury (DILI) preferred term or any death with ALT or AST ≥3xULN, bilirubin ≥2xULN or jaundice). IRs determined if the pEoI met the criteria for EoI classification by assessing DILI (definite, highly likely, probable, possible, unlikely, unrelated or undetermined), pattern (hepatocellular, mixed, cholestatic or undetermined), likely, competing or alternative cause(s), severity (mild, moderate, severe, fatal/transplantation or undetermined), Hy's law case, recovery \& liver failure (all yes, no or undetermined).

Pre-specified opportunistic infection events were adjudicated by blinded committees of external experts. pEoI were identified by investigator, sponsor \& search of SAE listings for serious infections coded to MedDRA infections \& infestations SOC \&/or events meeting pre-specified criteria for IR pre-screening to determine if adjudication is required. IRs determined if the pEoI met the criteria for EoI classification according to definitions for opportunistic infections (invasive fungal infections per the European Organization for Research \& Treatment of Cancer/Invasive Fungal Infections Cooperative Group \& the National Institute of Allergy \& Infectious Diseases Mycoses Study Group \[EORTC/MSG\] Consensus Group definitions, endemic fungal infections per the EORTC/MSG Consensus Group definitions, other fungal infections, viral, bacterial \& parasitic infections \& vaccine dissemination) \& special interest infections (actinomycosis, Legionella \& mononucleosis-like toxoplasmosis).

Pre-specified GI perforation events were adjudicated by committees of external experts who were blinded to treatment assignment. The pEoI were identified via search of AE/SAE listings using the MedDRA GI Perforation SMQ. The IRs determined if the pEoI met the criteria for EoI classification based on whether a GI perforation occurred and if yes, the location within the GI tract, possible contributing medical conditions and/or concomitant medications.

Pre-specified ILD events were adjudicated by committees of external experts who were blinded to treatment assignment. pEoI were identified by searches of the clinical, safety \& laboratory databases (AEs coded to the MedDRA ILD SMQ and events nominated by the study clinician or clinical lead). The IRs determined if the pEoI met the criteria for EoI classification by assessment of the ILD event (probably ILD, possible ILD, alternative diagnosis likely, other or insufficient information to classify).

Clinical response-100 was defined as a reduction in CDAI score of at least 100 points from baseline of the parent A3921083 study. Clinical remission was a CDAI score \<150 points. CDAI is a composite index consisting of a weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extra-intestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's diary kept while on study. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity.

Clinical remission was a CDAI \< 150 points. CDAI is a composite index consisting of a weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extra-intestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's diary kept while on study. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. The 15 mg BID treatment group was closed to further enrolment early on in the study by Protocol Amendment 5 after only 16 participants were enrolled into this group. Therefore, the efficacy analysis was not performed for this group because the results may be difficult to interpret due to the small sample size.

Satisfactory humoral response to the pneumococcal vaccine was defined as greater than or equal to (\>=) 2 fold increase in antibody concentrations from vaccination baseline (Day 29) in at least 6 of 12 pneumococcal antigens (1, 3, 4, 5, 6B, 7F, 9V, 14, 19A, 19F, 23F, 18C). Data was stratified by the background methotrexate use.

Satisfactory humoral response to the influenza vaccine was defined as \>= 4 fold increase in antibody titers from vaccination baseline (Day 29) in at least 2 of 3 influenza antigens (B, H1N1, H3N2). Data was stratified by the background methotrexate use.

Target plaque was evaluated individually for signs of induration, scaling and erythema. Each of the 3 signs was rated on 5-point severity scale ranged from 0 to 4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. The individual signs severity sub scores were summed to calculate TPSS. The total score varied in increments of 1 and ranged from 1 to 12, with higher scores representing greater severity of psoriasis.

Based on the National Eye Institute (NEI) dry eye clinical trials workshop, the cornea was divided into 5 different zones. Each corneal zone was graded independently using a 0 to 3 grading scale:0=none, 1=slight, 2=moderate, 3=severe. Sum of scores of each zone led to total score. Total score range: 0 to 15, higher score indicated greater staining. Results from study eye are reported. The study eye was defined as the eye with the worse (higher) corneal staining score at baseline. Change: score at observation minus score at baseline. Negative change from baseline indicated improvement.

Synovial tissue biopsy were performed and assayed for mRNA gene expression by quantitative polymerized chain reaction (PCR) using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Interleukin-1beta (IL-1beta), IL-6, matrix metalloproteinase-3 (MMP3), cluster of differentiation 19 (CD19), cluster of differentiation 3 epsilon (CD3E), Janus kinase 1 (JAK1), JAK2, JAK3, signal transducers, activators of transcription (STAT1), interferon stimulated gene 15 (ISG15), C-X-C motif chemokine 10 (CXCL10), chemokine (C-C motif) ligand2 (CCL2), phospho-STAT1 (pSTAT1), pSTAT3, tumor necrosis factor alpha (TNFalpha), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) presented as control gene normalized expression (relative expression) within synovial tissue.

Synovial tissue biopsy was to be performed and assayed for protein expression by quantitative PCR using standard curve method. Standard curve was to be generated by linear regression using log threshold cycle versus log (cell number). TNFalpha, IL-6, IL-17 and IL-10 data were to be presented as control normalized expression (relative expression) within synovial tissue.

The intensity of CD3 and CD68 cell infiltration was expressed as the percentage area of the tissue section occupied by positively stained cells. Surface marker CD68 macrophages and CD3 thymus cells (T cells) in the inflammatory cells of synovial tissue were detected by immunohistochemical staining.

Blood levels were utilized for expression analysis (mRNA) of following genes that reflect immune function: CD19, CD3 epsilon (CD3E), STAT1, STAT3, ISG15, CXCL10. mRNA gene expression in blood were assayed by quantitative PCR using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Data were presented as control gene normalized expression (relative expression) within blood.

Blood levels were utilized for expression analysis (mRNA) of following genes that reflect immune function: CD19, CD3E, STAT1, STAT3, ISG15, CXCL10. mRNA gene expression in blood were assayed by quantitative PCR using standard curve method. Standard curve generated by linear regression using log threshold cycle versus log (cell number). Data were presented as control gene normalized expression (relative expression) within blood.

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, active 70 kDa (p70) form of IL-12(IL-12p70), interferon gamma (IFNgamma) - induced protein 10 (IP-10), TNFalpha, granulocyte macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein 1 alpha (MIP1a), monocyte chemotactic protein 1 (MCP1), soluble vascular endothelial growth factor (sVEGF), soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), granulocyte colony-stimulating factor (G-CSF) was measured by immunoassay and the levels were expresses as picogram per milliliter (pg/mL).

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Blood samples were collected from all the participants and pro-inflammatory cytokine levels were measured. The levels of pro-inflammatory cytokine IL-1beta, IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-7, IL-21, IL-12p70, IP-10, TNFalpha, IFNgamma, GM-CSF, MIP1a, MCP1, sVEGF, sVCAM-1, sICAM-1, G-CSF was measured by immunoassay and the levels were expresses as pg/mL.

Blood samples were collected for fluorescence-activated cell sorting \[FACS\] analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, Bone-marrow cells (B cells) and natural killer (NK) cells were analyzed using fluorescent-labeled antibodies against clusters of differentiation (CD) markers.

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Blood samples were collected for FACS analysis of lymphocyte subsets. Lymphocyte subset counts of T cells, B cells and NK cells were analyzed using fluorescent-labeled antibodies against CD markers.

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific Enzyme-Linked Immunosorbent Assay \[ELISA\] method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples).

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Blood/serum samples were analyzed for MMP3, osteocalcin and osteopontin concentrations using a validated analytical assay sensitive and specific ELISA method for MMP3 and osteopontin in serum samples; specific electrochemiluminescence method for osteocalcin in blood samples.

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Plasma samples were analyzed for PTH concentrations using a validated, sensitive and specific electrochemiluminescence method.

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Blood samples were analyzed for OPG concentrations using a validated, sensitive and specific ELISA method.

Serum samples were analyzed for SAA concentrations using meso scale discovery (MSD) single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific Electro ChemiLuminescent ImmunoAssay (ECLIA).

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Serum samples were analyzed for SAA concentrations using MSD single ELISA electrochemiluminescence method and for CTX-1 concentrations using a validated, sensitive and specific ECLIA.

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Serum samples were analyzed for IL-1ra and IL-15 concentrations using a validated, sensitive and specific ELISA method.

Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as nanogram per millimoles of creatinine (ng/mmol Cr).

Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

Urinary concentration of collagen type II C-telopeptide fragments was measured by competitive ELISA. uCTX-II was measured as ng/mmol Cr.

ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in painful and tender joint count; \>= 20% improvement in swollen joint count; and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).

Clinically significant infection was defined as the presence of documented infection confirmed by culture, biopsy, genomic, or serologic findings post-randomization and requiring hospitalization or parenteral anti-infective treatment, or otherwise deemed significant by the investigator. The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.

All treatment-emergent malignancies in Study A3921050 were included as collected on the Malignancy Case Report Form page.

Glomerular filtration rate (GFR): an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using iohexol serum clearance. For determination of iohexol serum clearance, iohexol was administered as an intravenous (IV) bolus over 5 minutes immediately after morning dosing of Tofacitinib or CsA on day of GFR evaluation. Blood samples for iohexol (3 millilitres \[mL\] each to provide a minimum of 1 mL serum) were collected into appropriately labeled tubes containing no additives at 120, 180, 240, and 300 minutes after the end of the iohexol IV bolus. A normal GFR is greater than (\>) 90 mL/min, although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR less than (\<) 15 mL/min indicated kidney failure.

Progression of chronic allograft lesions was defined as an increase in the Banff chronicity score (Banff-CS) in biopsy from the implantation (baseline) biopsy in a given participant. Banff-CS was the sum of the Banff scores for the 4 chronic basic lesions (allograft glomerulopathy \[cg\] + interstitial fibrosis \[ci\] + tubular atrophy \[ct\] + vascular intimal thickening \[cv\]). The Banff-CS ranged from 0-12, higher score indicated greater lesions and Month 36 Banff-CS greater than the implantation biopsy score indicated progression of lesions.

BPAR was category acute rejection as interpreted by the central blinded pathologist according to the Banff 97 working classification. The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.

Treated clinical acute rejection was defined as an acute rejection episode that was diagnosed based on local biopsy readout and received anti-rejection treatment. The 'Number' and 'Other Confidence Interval Level' columns represent cumulative proportions and 60% confidence intervals (CIs) as estimated from the fitted Kaplan-Meier curves for each treatment at scheduled visits.

Combined assessment of lesion severity and area affected into single score; range=0(no disease)-72(maximal disease). Body divided into 4 sections=head, upper/lower limbs, trunk; each area scored by itself and scores combined for final PASI. For each section percent area of skin involved was estimated:0(0%) - 6(90-100%) and severity estimated by clinical signs of erythema, induration, scaling; ranged 0-4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. Final PASI=sum of severity parameters for each section\*area score\*weighing factor(head=0.1, upper limbs=0.2, trunk=0.3, lower limbs=0.4).

Clinical response 70: defined as a reduction in Crohn's Disease Activity Index (CDAI) score from baseline of at least 70 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity.

ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in tender joint count (TJC); \>= 20% improvement in swollen joint count (SJC); and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).

Clinical BPAR was a BPAR (category acute rejection as interpreted by the central blinded pathologist according to the Banff 97 working classification) associated with an increase in serum creatinine of \>= 0.3 milligram per deciliter (mg/dL) and \>=20 percent (%) from pre-rejection baseline. The increase in serum creatinine was assessed based on the comparison of baseline and the highest serum creatinine recorded within 24 hours (hrs) of the time of biopsy.

GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using iohexol serum clearance. For determination of iohexol serum clearance, iohexol was administered as an intravenous bolus over 5 minutes immediately after morning dosing of CP-690,550 or CsA on day of GFR evaluation. A normal GFR is greater than (\>) 90 milliliter per minute (mL/min), although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR less than (\<) 15 mL/min indicated kidney failure.

GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using MDRD equation. GFR by MDRD equation = 170 \* (serum creatinine \[in milligrams per deciliter (mg/dL)\])\^(-0.999) \* (age in years)\^(-0.176) \* (0.762 if female) \* (1.18 if black) \* (blood urea nitrogen \[BUN\] concentration \[mg/dL\])\^(-0.170) \* (serum albumin concentration \[in grams per dL (g/dL)\])\^(0.318). A normal GFR is \>90 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2), although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR \<15 mL/min/1.73 m\^2 indicated kidney failure.

Kaplan-Meier analysis of percentage of participants with clinically significant infections by time to first clinically significant infection within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier.

Kaplan-Meier analysis of time to NODM-1 within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. NODM-1 was defined as an event experienced by participants who were non-diabetic prior to transplantation and required treatment with oral hypoglycemic agents, anti-diabetic agents, and/or insulin for greater than or equal to (≥)30 days.

Hypercholesterolemia was defined as cholesterol levels \>240 mg/dL or 6.2 mmol/L.

Hypertriglyceridemia was defined as triglyceride levels of \>200 mg/dL or 2.3 mmol/L.

Kaplan-Meier analysis of percentage of participants with treatment failure by time to treatment failure within 96 months post-transplant. Time was defined from the date of first dose of study drug in Study A3921009 to the date of first occurrence of the event, censored at the day of the last visit or Day 2980 (the maximum scheduled day for follow-up 98 month), whichever comes earlier. Treatment failure was defined as the first occurrence of BPAR, death, graft loss or premature discontinuation of trial medication for any reason.

BPAR categorized as acute rejection as interpreted by the central blinded pathologist according to the Banff 97 working classification.

GFR: index of kidney function described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR was calculated by creatinine clearance (CLcr) using Nankivell equation. CLcr by Nankivell equation= (6.7 per serum creatinine) plus (0.25\*body weight) minus (0.5\*serum urea) minus (100 per square height) plus (35 for male/25 for female). A normal GFR is \>90 milliliter/minute (mL/min), although children and older people usually have a lower GFR. Lower values indicated poor kidney function. A GFR \<15 mL/min indicated kidney failure.

ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in tender joints count (TJC); \>= 20% improvement in swollen joints count (SJC); and \>= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire \[HAQ\]); and C-Reactive Protein (CRP).

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is also influenced by the fraction of the dose absorbed. Clearance was estimated by non compartmental analysis (NCA) of PK data. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. It was calculated by dividing the given oral dose by AUCtau. AUCtau is the area under the plasma concentration time-curve from time zero to end of dosing interval.

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A 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. Treatment emergent AEs included both serious and non-serious AEs.

Criteria for vital signs of potentially clinical concern included supine/sitting pulse rate of \<40 beats per minute (bpm) or \>120 bpm, standing pulse rate of \<40 bpm or \>140 bpm, systolic blood pressure of \>=30 millimeters of mercury (mmHg) change from baseline and systolic blood pressure \<90 mmHg, diastolic blood pressure \>=20 mmHg change from baseline and diastolic blood pressure \<50 mm Hg.

Blood level of HDL-C was measured following a 12-hours fasting.

Blood level of HDL-C was measured following a 12-hours fasting.

Cholesterol ester production rate was calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.

Cholesterol ester production rate was calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Systemic AEs are the events which are not localized but occur throughout the systemic circulation.

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Ocular AEs are the events which are localized in the ocular region.

Ocular tolerability assessment included evaluation of severity and duration of the 5 symptoms: burning/stinging, blurred vision, ocular discomfort, pain, tearing. Severity was assessed on a 4-point scale, where 0=none, 1=mild, 2=moderate and 3=severe. Duration was assessed as immediate (if subsided within 5 minutes \[\<5 min\] after application) or persistent (if continued beyond 5 minutes \[\>=5 min\] after application).

Schirmer test without anesthesia: well standardized test used to estimate tear flow stimulated reflexly by insertion of a filter paper strip into the conjunctival sac for 5 min. The length of wetting was recorded to the nearest 0.5 millimeter (mm). If the wetting line was oblique, halfway point was used. Results from study eye are reported. Study eye is the 'worse eye', defined as the eye with worse Schirmer test score without anesthesia score at baseline.

Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to the beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as Least Squares (LS) mean difference (CP-690,550 minus Placebo, baseline-adjusted).

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The QT interval was adjusted for RR interval using the QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Data is reported as LS mean difference (CP-690,550 minus Placebo, baseline-adjusted).

AUC (0-12)= area under the plasma concentration time-curve from time zero (pre-dose) to 12 hours (0-12).

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Renal clearance is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time.

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) at steady state.

Area under the plasma concentration time-curve from zero to 12 hour concentration \[AUC(0-12)\] at steady state.

Rac obtained from AUC(0-12) (Day 29) divided by AUC(0-12) (Day 1).

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half at steady state.

Pro-drug MMF was metabolically converted to active form MPA in the liver. The baseline for MPA trough concentrations was defined as the average of the values obtained at Screening and on Day 1 (pre-dose). MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.

Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.

Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.

Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.

Pro-drug MMF was metabolically converted to active form MPA in the liver. MPA levels were assessed at different visits to assess change in MPA trough levels due to CP-690,550 exposure.

The baseline for CsA trough concentrations was defined as the average of the values obtained at Screening and on Day 1 (pre-dose). CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.

CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.

CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.

CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.

CsA levels were assessed at different visits to assess change in CsA trough levels due to CP-690,550 exposure.

The baseline for TAC trough concentrations was defined as the average of the values obtained at Screening and on Day 1 (pre-dose). TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.

TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.

TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.

TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.

TAC levels were assessed at different visits to assess change in TAC trough levels due to CP-690,550 exposure.

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. It was calculated by dividing given dose of drug with AUC.

Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided (/) by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm).

Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm).

Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm).

Dialyser clearance was calculated as amount of drug in dialysate collected over a period of time (AHD) divided by the product of fraction unbound of drug in plasma (fu), corresponding mid-time plasma concentration of drug (Cmid), and duration of dialysate collection period (tm). CL HD = AHD/(fu\*Cmid\*tm).