tofacitinib

Remission is defined by central endoscopy read Mayo score of 2 points or lower, with no individual subscore exceeding 1 point and a rectal bleeding subscore of 0. The primary outcome Mayo score is the summation of 4 subscores as listed below : * patient reported stool frequency (scored 0 to 3) * patient reported rectal bleeding (scored 0 to 3) * central read findings on endoscopy (scored 0 to 3) * physician's global assessment (scored 0 to 3) The Mayo score has a scale from 0 to 12 points, with the lower score indicating lower ulcerative colitis (UC) disease activity.

Clinical remission was based on the modified Mayo score (MMS). The MMS is a composite score of 3 assessments consisting of participant-reported symptoms using daily electronic (e)-diary and centrally read endoscopy: stool frequency (SF), rectal bleeding (RB) and endoscopic score (ES). Clinical remission was defined as SF sub-score = 0 (or = 1 with a greater than or equal to \[\>=\] 1-point decrease from Baseline), RB sub-score = 0, and ES less than or equal to (\<=) 1 (excluding friability). Each component sub-score ranged from 0 to 3 and total score range of the MMS was from 0 to 9, with higher scores indicating more severe disease.

Safety as assessed by the evaluation of adverse events

ACR50 response: greater than or equal to (≥) 50% improvement in tender (TJC) and swollen joint counts (SJC) and ≥50% improvement in 3 of the 5 remaining ACR-core set measures: patient (PtGA) and physician global assessments (PhyGA), pain, disability (Health Assessment Questionnaire - Disability Index \[HAQ-DI\], scored from 0 to 3), and an acute-phase reactant (C-reactive protein \[CRP\]). TJC was based on 68 joints and SJC was based on 66 joints. PtGA, PhyGA and Pain were VAS on a scale of 0-100 millimeter (mm).

ASAS20 assess 4 domains: Patient Global Assessment of Disease (PGA) (assess disease activity on a scale of 0 \[not active\] to 10 \[very active\], high score=more disease activity), total back pain (scale of 0 \[no pain\] to 10 \[most severe pain\], high score=more severity), Function (Bath Ankylosing Spondylitis Functional Index \[BASFI\]; participant's level of ability on scale of 0 \[easy\] to 10 \[impossible\], low score= better functional health) and Inflammation (morning stiffness, Mean of Question \[Q\]5 and Q6 of Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] defined as 6-item questionnaire measure disease activity on a scale of 0 \[none\] to 10 \[severe\], high score=more disease activity). ASAS20 response: greater than or equal to (\>=) 20 percent (%) improvement from baseline in disease activity and absolute change of \>=1 unit in \>=3 domains and no worsening of \>=20% and an absolute change of \>=1 unit in remaining domain.

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joints count, CRP (milligrams per liter \[mg/L\]) and patient global assessment of disease activity on a 100 millimeter (mm) visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \[less than or equal to\] \<= 3.2 implied low disease activity and greater than (\>) 3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (CRP) less than (\<) 2.6 implied remission.

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 48 months that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious AEs.

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. AEs were classified into 3 categories according to their severity as mild AEs (did not interfere with participant's usual function), moderate AEs (interfered to some extent with participant's usual function) and severe AEs (interfered significantly with participant's usual function).

Laboratory tests: hematology (Hb, hematocrit, RBC count, platelets, reticulocytes, WBC count, count and absolute lymphocytes,neutrophils, basophils, eosinophils, monocytes. Liver function (bilirubin \[total, direct, indirect\], AST, ALT, alkaline phosphatase, gamma-glutamyl transferase, albumin, total protein), renal function (blood urea nitrogen, creatinine), Lipids (cholesterol, HDL, LDL, triglyceride, apolipoprotein \[A-1, B\]), electrolytes (sodium, potassium, chloride, calcium, biocarbonate), chemistry (glucose, HbA1c, creatinine kinapse), urinalysis dipstick(urine pH, glucose, ketones, protein, blood, leukocyte, esterase), urinalysis microscopy (urine- RBC, WBC, bacteria, epithelial cells),C-reactive protein. Laboratory abnormality: determined by investigator per pre-defined criteria.

Laboratory tests: hematology (Hb, hematocrit, RBC count, platelets, reticulocytes, WBC count, count and absolute lymphocytes, neutrophils, basophils, eosinophils, monocytes. Liver function (bilirubin\[total,direct,indirect\], AST, ALT, alkaline phosphatase, gamma-glutamyl transferase, albumin, total protein), renal function (blood urea nitrogen, creatinine), Lipids(cholesterol, HDL, LDL, triglyceride, apolipoprotein \[A-1, B\]), electrolytes (sodium, potassium, chloride, calcium, biocarbonate), chemistry (glucose, HbA1c, creatinine kinapse), urinalysis dipstick(urine-pH, glucose, ketones, protein, blood, leukocyte, esterase), urinalysis microscopy(urine- RBC, WBC, bacteria, epithelial cells),C-reactive protein. Clinically significant change: determined by investigator per pre-defined criteria.

HAQ-DI assessed the degree of difficulty a participant had experienced during the past week in 8 domains of daily living activities: dressing/grooming, arising, eating, walking, reach, grip, hygiene, and other activities. There were total of 2-3 items distributed in each of these 8 domains. Each item was scored for level of difficulty on a 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible HAQ-DI score ranged from 0 (least difficulty) to 3 (extreme difficulty), where higher score indicated more difficulty while performing daily living activities.

PASDAS was composite PsA disease activity score that included following components: Physician and patient global assessment of disease activity (assessed on a 0-100 VAS) in millimeter (mm), swollen (66 joints) and tender joint counts (68 joints), Leeds enthesitis index (enthesitis assessed at 6 sites; total score of 0-6), tender dactylitic digit score (scored on a scale of 0-3, where 0= no tenderness and 3= extreme tenderness), short form-36 questionnaire (SF-36) physical component summary (norm-based domain scores were used in analyses; with a population mean of 50 with a SD of 10 points, and ranges from minus infinity to plus infinity) and C-reactive protein (CRP) in milligram per liter (mg/L). PASDAS was composite score and was a weighted index with score range of 0 to 10, where higher score indicated more severe disease.

ACR20 was calculated as a ≥20% improvement from baseline in tender/painful and swollen joint counts and ≥20% improvement from baseline in 3 of the 5 remaining ACR core set measures: patient's global assessment of arthritis, physician's global assessment of arthritis, patient's assessment of arthritis pain, health assessment questionnaire - disability index (HAQ-DI), and C-reactive protein (CRP).

The HAQ-DI assesses the difficulty a participant has had in the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2-3 items. For each question, level of difficulty is scored from 0 to 3 with 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. The score for each domain is the maximum (worst) score from the items/questions within the domain. Higher score indicates greater disability.

ACR20 was calculated as a ≥20% improvement from baseline in tender/painful and swollen joint counts and ≥20% improvement from baseline in 3 of the 5 remaining ACR core set measures: patient's global assessment of arthritis, physician's global assessment of arthritis, patient's assessment of arthritis pain, Health Assessment Questionnaire - Disability Index (HAQ-DI), and C-reactive protein (CRP).

The HAQ-DI assesses the difficulty a patient has had in the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2-3 items. For each question, level of difficulty is scored from 0 to 3 with 0=no difficulty, 1=some difficulty, 2=much difficulty, and 3=unable to do. The score for each domain is the maximum (worst) score from the items/questions within the domain. Higher score indicates greater disability. Overall score was computed as the sum of the domain scores divided by the number of domains answered. The total possible score ranged from 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Higher overall score indicates greater disability.

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 is an instrument designed to measure disease activity of Ulcerative Colitis . It consisted of 4 subscores: stool frequency, rectal bleeding, findings of centrally read flexible proctosigmoidoscopy and physician global assessment (PGA), each graded from 0 to 3 with higher scores indicating more severe disease. These scores were summed up to give a total score range of 0 to 12; where higher score indicating more severe disease.

The proportion of patients with at least 1 episode of acute pouchitis during the 48 weeks of treatment. Acute Pouchitis defined as: modified pouchitis disease activity index (mPDAI) score ≥ 5 points OR an increase of ≥ 2 points vs. baseline, AND Endoscopic component of the mPDAI Score \>= 2 points (within 7 days prior or post the collection date of the symptomatic component of the mPDAI score)

Clinical remission was defined as a total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point (SF= 1 or 0), ES=1 or 0 and RB=0. Mayo score: instrument designed to measure disease activity of ulcerative colitis. will be summarized by the number and percentage of participants achieving the response, along with a two-sided 95% CI.

Clinical remission:Participants with stool frequency (SF)subscore=0(or of 1 with greater than or equal to(\>=)1 point decrease from baseline,rectal bleeding(RB)subscore=0 and endoscopic score(ES)less than or equal to(\<)=1(excluding friability).SF subscore:number of stools in 24-hours relative to normal number of stools for that participant in same period,score ranged from 0(normal number of stools) to 3(5 or more stools than normal),higher scores=more severity.RB subscore:most severe amount of blood passed per rectum in 24-hours,score ranged from 0(no blood seen)to 3(blood alone passes),higher scores=more severity.ES:reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy,score ranged from 0(normal or inactive disease) to 3(severe disease \[spontaneous bleeding,ulceration\]),higher scores=more severity.Modified Mayo score:measure disease activity for UC,score:0(normal) to 9(maximum severity),comprised subscores for SF,RB,ES.higher score=more severe disease activity.

MMS is used to assess disease activity in participants with UC and has following components: endoscopic score(ES),rectal bleeding(RB),stool frequency(SF).Each component score ranges from 0 to 3(0=normal,1=mild,2=moderate,3=severe); higher scores indicating more severe disease.ES reported worst appearance of mucosa on flexible sigmoidoscopy or colonoscopy,scores ranged from 0(normal or inactive disease) to 3(severe disease \[spontaneous bleeding, ulceration\]).RB reported most severe amount of blood passed per rectum in 24-hour period,scores ranged from 0(no blood seen) to 3(blood alone passes).SF reported number of stools in 24-hour period relative to normal number of stools for that participant in same period,scores ranged from 0(normal number of stools) to 3(5 or more stools than normal).CR per FDA draft guidance defined as:SF=0 or 1 and no greater than baseline, RB=0,ES less than or equal to (\<=)1(excluding friability).Percentage of participants achieving CR at Week 52 was evaluated.

Eosinophils was counted in the areas of greatest eosinophil density. Counts were reported as the number of eosinophils/high power field (eos/hpf) and multiple hpfs analyzed until the PEC was clearly identified after taking into account all biopsies from all esophageal levels.

SALT I is a well-validated metric used to determine the degree of hair loss based on the percentage (%) of scalp surface area involved on the top (40%), back (24%), left side (18%) and right side (18%) of the scalp for AA. Investigator determines the % scalp hair loss in a given quadrant, multiply this by the total scalp area delineated by that quadrant, and sum the resultant numbers for each quadrant to give the total % scalp hair loss with a maximum score of 100. Score range from 0% (no scalp hair loss) to 100% (complete scalp hair loss), higher scores indicated more scalp hair loss. Percent change from baseline in SALT I is reported in terms of Least square mean and standard error.

VZV-specific IgG levels as measured by enzyme-linked immunosorbent assay (ELISA).

The EASI quantifies the severity of a participant's atopic dermatitis based on both lesion severity and the percent of BSA affected. The EASI is a composite scoring by the atopic dermatitis clinical evaluator of the degree of erythema, induration/papulation, excoriation, and lichenification (each scored separately) for each of 4 body regions, 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 EASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of atopic dermatitis. What is reported is the percent change from baseline in EASI scores.

Clinical signs of plaque psoriasis (erythema \[E\], induration \[I\], and scaling \[S\]) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. The PGA-C was a static assessment; i.e., without regard to a previous assessment. The PGA subscores are then summed and averaged after which the total average was rounded to the nearest whole number to determine the PGA-C score and category. A higher score indicated a higher level of severity. 0 is equal to (=) cleared except for any residual discoloration and 1=almost clear, majority of lesions had individual scores for E+I+S that when summed, averaged, and rounded equaled 1.

Clinical signs of plaque psoriasis (E, I, and S) were scored separately according to a 5-point severity scale (0 to 4) to provide PGA subscores, which described the overall severity of each clinical sign. The PGA-C was a static assessment; i.e., without regard to a previous assessment. The PGA subscores are then summed and averaged after which the total average was rounded to the nearest whole number to determine the PGA-C score and category. A higher score indicated a higher level of severity. 0 is equal to (=) cleared except for any residual discoloration and 1=almost clear, majority of lesions had individual scores for E+I+S that when summed, averaged, and rounded equaled 1.

The primary analysis of this outcome measure was performed using the Emax model. Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of greater than or equal to (≥) 20% and ≥1 unit in at least 3 domains (on a scale of 0 \[least\] to 10 \[worst\]) and no worsening of ≥20% and less than or equal to (≤)1 unit in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity, spinal pain, function and inflammation (from Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Missing data were handled by nonresponsive (NRI)/ last observation carried forward (LOCF). Missing values due to a subject dropping out from the study were handled by setting the ASAS20 value to NRI. The LOCF approach was applied to missing components, if just some of the components of the ASAS20 were missing.

The supportive analysis of this outcome measure was performed using the normal approximation for two proportions. Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of ≥ 20% and ≥1 unit in at least 3 domains (on a scale of 0 \[least\] to 10 \[worst\]) and no worsening of ≥20% and ≤1 unit in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity, spinal pain, function and inflammation (from Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\]). Missing data were handled by NRI/LOCF. Missing values due to a subject dropping out from the study were handled by setting the ASAS20 value to NRI. The LOCF approach was applied to missing components, if just some of the components of the ASAS20 were missing.

Parameters: Hematology (hemoglobin, hematocrit, erythrocytes, platelets, leukocytes, lymphocytes, lymphocytes/leukocytes, neutrophils, neutrophils/leukocytes, basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, monocytes, monocytes/leukocytes, prothrombin international normalized ratio, erythrocyte sedimentation rate), clinical chemistry (bilirubin, direct/indirect bilirubin, aspartate/alanine aminotransferase, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase, protein, albumin, blood urea nitrogen, creatinine, cholesterol, high and low density lipoprotein cholesterol, Friedewald estimation, triglycerides, sodium, potassium, chloride, calcium, bicarbonate, glucose, creatine kinase, C reactive protein), urinalysis (specific gravity, potential of hydrogen (pH), glucose/ protein/ hemoglobin/ erythrocytes/ leukocytes, ketones, leukocyte esterase, hyaline casts, bacteria). Number of participants with at least 1 laboratory abnormality are reported.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily had a causal relationship with the treatment or usage. A serious AE (SAE) was defined as any untoward medical occurrence at any dose that met one or more of the following criteria: resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect. An TEAE was any AE that occurred following the start of study treatment in this study or increased in severity following the start of study treatment in this study. AE included both SAEs and all non-SAEs.

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Body weight was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Height was collected to assess growth and physical development. Baseline value was based on the enrollment gap: either from the qualifying studies (A3921103 \[NCT01513902\], A3921104 \[NCT02592434\], or A3921165 \[NCT03000439\]) (when participants enrolled in the current extension study within 14 days of the last visit of the qualifying/ index study), or from the current extension study (A3921145 \[NCT01500551\]) (when enrollment was out of 14-day window).

Pubertal development was measured using Tanner stage, by age group (2 to \<6 years, 6 to \<12 years, and 12 years or older) for males and females separately. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (fully developed breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes continue to enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size).

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 12. Only rows with non-zero values were reported in this outcome measure.

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 24. Only rows with non-zero values were reported in this outcome measure.

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 36. Only rows with non-zero values were reported in this outcome measure.

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 48. Only rows with non-zero values were reported in this outcome measure.

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 60. Only rows with non-zero values were reported in this outcome measure.

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 72. Only rows with non-zero values were reported in this outcome measure.

Pubertal development was measured using Tanner stage, by age group and gender. Assessment included, 1) Male: pubic hair and size of genitalia and 2) Female: pubic hair and breast exam. There were 5 stages for each assessment type. Stages for, a) Pubic hair: 1 (no hair), 2 (downy hair), 3 (scant terminal hair), 4 (terminal hair filled entire triangle overlying pubic region), 5 (terminal hair extended beyond inguinal crease onto thigh); b) Breast exam: 1 (no breast development), 2 (breasts buds), 3 (breast tissue palpable outside areola; no areolar development), 4 (secondary mounds, separation of contours), 5 (full breast); c) Genitalia: 1 (no genital growth), 2 (enlargement of scrotum and testes), 3 (penis grow in size, testes enlarge), 4 (penis grow in length/ breadth, scrotum darkens, testes enlarge), 5 (adult shape and size). Number of participants are reported per shift in Tanner stage from Baseline to Month 84. Only rows with non-zero values were reported in this outcome measure.

Combined assessment of lesion severity and area affected into single score; range equals (=) 0 (no disease) to 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%) to 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) summed over all sections.

PGA psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. PGA of Psoriasis scale ranges from 0 (no psoriasis) to 4 (severe disease). ‘Clear’ and “Almost clear’ includes all participants who were scored as a 0 or 1.

Clinical response was defined as a decrease from baseline in Mayo score of at least 3 points and at least 30 percent, with accompanying decrease in subscore for rectal bleeding of at least 1 point or absolute subscore for rectal bleeding of 0 or 1. Mayo score: instrument designed to measure disease activity of ulcerative colitis. Total score range: 0 to 12; higher score=more severe disease. It consisted of 4 subscores: stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy and physician global assessment, each ranged from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe).

Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles. For each scheduled hour post morning dose (HPD), except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles. For each scheduled hour post morning dose (HPD), except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles. For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.Change from baseline in QT interval at HPD 16 was planned to be analyzed for participants who received CP-690,550 60 mg and matching placebo.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles. The mean of the triplicates at HPD=0 on Day 1 will be defined as the baseline for HPD=0.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated.QT interval: The time corresponding to the beginning of depolarization to repolarization of the ventricles.For each scheduled HPD, except for HPD=0, the time-matched baseline QT was defined as the mean of the triplicates on Day 0 at the same nominal HPD.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of 30 to less than (\<) 60 msec(borderline) and greater than or equal to (\>=) 60 msec (prolonged) were summarized.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum QTc \>=500 msec were reported.

AUCtau = area under the curve from time zero to end of dosing interval.

AUCtau = area under the curve from time zero to end of dosing interval.

Accumulation ratio was calculated as, R0 = area under the curve from time zero to end of dosing interval (AUCtau) on Day 14 divided by area under the curve from time zero to end of dosing interval (AUCtau) on Day 1.

Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

Absolute cell counts of cluster of differentiation 3 (CD3): T lymphocytes, cluster of differentiation 4 (CD4): Helper/Inducer T- Lymphocytes reactive with Major Histocompatability Complex-II (MHC-II), and cluster of differentiation 8 (CD8): Suppressor/Cytotoxic T-lymphocyte reactive with Major Histocompatability Complex-I (MHC-I), cluster of differentiation 16/56 (CD16/56): natural killer Cells, cluster of differentiation 19 (CD19): B-Lymphocytes determined using FACS.Baseline defined as mean of samples collected during screening, visit in which biopsy was taken, at Day 0 and at 0 hour Day 1.

The degree of immunosuppression induced by the study drug administration was evaluated using a bioluminescent assay in which the concentration of Adenosine-5-Triphosphate (ATP) released by CD4 cells was measured. ATP concentrations released from stimulated and unstimulated cells were evaluated. ATP Concentration less than or equal to (\<=) 225: low immune cell response, 226 to 524: Moderate immune cell response, \>= 525: strong immune cell response. Baseline was defined as the mean of the samples collected during the pre-dose biopsy.

Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

Reticulocyte count was assessed to detect potential of Janus kinase 2 (JAK2) mediated erythropoiesis.

EAUC 50 was calculated from a regression analyses using area under the concentration-time curve (AUC) as the independent variable. A sigmoid maximum effect (Emax) model was used to explain the relationship between AUC and modified Psoriasis Severity Index (mPASI) score, where Emax was the maximum effect (100 percent reduction in the total mPASI score from baseline), and EAUC 50 was the AUC where 50 percent of the maximum effect was measured.