Extension Study Of Subjects From Study A3921030 For The Prevention Of Acute Rejection In Kidney Transplant Patients

Kaplan-Meier Analysis of Percentage of Participants With Efficacy Failure by Visit

Efficacy failure was the first occurrence of BPAR diagnosed by the central pathologist or graft loss including participant death. BPAR (category acute rejection) was 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.

Time frame: Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Kaplan-Meier Analysis of Percentage of Participants With Combined Banff Rejection by Visit

Banff 97: standard classification for scoring and classifying rejection of kidney transplant biopsies in 6 diagnostic categories: normal, antibody-mediated rejection, borderline changes: 'suspicious' for acute cellular rejection, acute/active cellular rejection, chronic/sclerosing allograft nephropathy, and other. Combined Banff rejection was calculated from categories of antibody-mediated rejection (Category 2) plus borderline changes (Category 3) plus acute rejection (Category 4), as interpreted by the central pathologist. 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.

Time frame: Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Kaplan-Meier Analysis of Percent of Participants With Graft Survival With Death Censored by Visit

Graft loss was defined as graft nephrectomy, subject death, retransplantation, or return to dialysis for at least 6 consecutive weeks. 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. Included data up to 2 months postdose in the clinical Follow-up visit.

Time frame: Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Kaplan-Meier Analysis of Percentage of Participants Surviving by Visit

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. Included data up to 2 months postdose in the clinical Follow-up visit.

Time frame: Months 12, 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Percentage of Participants Discontinuing From the Study

Discontinuations were due to any reason including those occurring as a result of protocol Amendments 3 and 4.

Time frame: Months 12 through 72.

Least Squares Means of Total Serum Cholesterol Levels (Milligrams Per Deciliter [mg/dL]) by Visit

Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.

Time frame: Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Least Squares Means of Total Serum Low Density Lipoprotein (LDL) Cholesterol Levels (mg/dL) by Visit

Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.

Time frame: Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Least Squares Means of Total Serum High Density Lipoprotein (HDL) Cholesterol Levels (mg/dL) by Visit

Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.

Time frame: Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Least Squares Means of Total Serum Triglycerides (mg/dL) by Visit

Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.

Time frame: Month 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Mean Absolute Neutrophil Counts (ANC) (Kelvin Per Millimeter Cubed [K/mm^3]) by Visit

Follow-up visit included Month 74 visit for completers and 2-month postdose visit for early withdrawals.

Time frame: Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 and Follow-up

Mean Hemoglobin (Hgb) (Grams Per Deciliter [g/dL]) by Visit

Follow-up visit included Month 74 visit for completers and 2-month postdose visit for early withdrawals.

Time frame: Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72 and Follow-up

Mean Glycosylated Hemoglobin (HBA1c) (Percent [%]) by Visit

HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. The normal range for the HbA1c test is between 4% and 5.6%. HbA1c levels between 5.7% and 6.4% indicate increased risk of diabetes and levels of 6.5% or higher indicate diabetes.

Time frame: Months 24, 36, 48, 60, 72

Least Squares Means of Fasting Serum Glucose Levels (mg/dL) by Visit

Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A compund symmetry variance-covariance structure was used.

Time frame: Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Percentage of Participants by Proteinuria Category by Visit

Proteinuria was defined as the presence of an excess of serum proteins in the urine. Normal value of proteinuria is below 0.15 grams per 24 hours (g/24 hr). Follow-up visit included Month 74 visit for completers and 2-month postdose visit for early withdrawals.

Time frame: Months 24, 36, 48, 60, 72 and Follow-up

Least Square Means of Estimated GFR Calculated Using the Nankivell Equation by Visit

GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR was calculated using Nankivell formula, where: Creatinine clearance (mL/min) = 6.7/serum creatinine (millimols per litre \[mmol/L\]) - serum urea (mmol/dL)/2 + actual body weight (kilograms \[kg\])/4 - 100/Height (metres \[m\])\^2 + (35 for male or 25 for female). A normal GFR for adults is \> 90 mL/min. Lower values indicate poor kidney function. A GFR \<15 is consistent with kidney failure. Model contained treatment, visit and treatment by visit interaction as fixed effects. An unstructured variance-covariance structure was used.

Time frame: Month 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Least Squares Means of Estimated GFR Calculated Using the Cockcroft-Gault Equation by Visit

GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was measured directly or estimated using established formulas. GFR (mL/min) was calculated using Cockcroft-Gault equation. GFR by Cockcroft-Gault equation= body weight (kg)\*(140 minus age in years) divided by (72\*serum creatinine \[mg/dL\]). For females value obtained was multiplied by 0.85. A normal GFR is \>90 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. Model contained treatment, visit and treatment by visit interaction as fixed effects. An unstructured variance-covariance structure was used.

Time frame: Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Least Squares Means of Estimated GFR (eGFR) (mL/Min/1.73 Square Meter [m^2]) Calculated by the Modification of Diet in Renal Disease (MDRD) Equation With Last Observation Carried Forward (LOCF) Plus Imputation (eGFR=0 for Graft Loss/Death) by Visit

GFR: an index of kidney function. GFR described the flow rate of filtered fluid through the kidney. GFR was calculated using MDRD equation. GFR (mL/min/1.73 m\^2) by MDRD equation = 170 \* (serum creatinine \[mg/dL\])\^(-0.999) \* (age in years)\^(-0.176) \* (0.762 if female) \* (1.18 if black) \* (blood urea nitrogen concentration \[mg/dL\])\^(-0.170) \* (serum albumin concentration \[g/dL\])\^(0.318). A normal GFR is \>90 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. Model contained treatment, visit and treatment by visit interaction as fixed effects. An unstructured variance-covariance structure was used.

Time frame: Months 15, 18, 24, 30, 36, 42, 48, 54, 60, 66, 72

Least Squares Means of Short Form 36 Version 2 (SF-36 V2) Component and Domain Scores at Months 24 and 36

SF-36 v2 is a self-administered 36-item generic health status measure with 8 general health concepts which are the weighted sums of the questions in their section: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health. Each scale is transformed into a 0 (minimum) to 100 (maximum) scale on the assumption each question carries equal weight. These concepts were also summarized into 2 summary scores; Physical Component Summary and Mental Component Summary (both a 0-100 scale). The 8 subscales, 2 summary scores and transition Question 2 (TR Scale, measured on a scale of 1 \[minimum\] to 5 \[maximum\]) were subjected to analysis. Higher domain, summary scores, and TR scale scores indicate better health status. Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. First-order autoregressive variance-covariance structure was used.

Time frame: Months 24, 36

Least Squares Means of End-Stage Renal Disease (ESRD) Symptom Checklist (SCL) -Transplantation Modules at Months 24 and 36

ESRD-SCL: a 43-item disease specific self-administered questionnaire. Participants' rated the question "At the moment,how much do you suffer?" for each item on a 5 point scale, range (Ra) from 0 (not at all) to 4 (extremely). Consisted of 6 subscales: Cardiac and Renal (CR) dysfunction; Ra 0 to 28, Increased(In) Growth of Gum and Hair (IGGH); Ra 0 to 20, Limited Cognitive Capacity (LCC); Ra 0 to 32, Limited Physical Capacity (LPC); Ra 0 to 40, Side Effects (SEs) of Corticosteroids; Ra 0 to 20, Transplantation Associated Psychological Distress (TAPD); Ra 0 to 32. Total Score: 0 to 172, higher scores indicate greater dysfunction. Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.

Time frame: Months 24, 36

Least Squares Means of Severity of Dyspepsia Assessment (SODA) Subscales at Months 24 & 36

SODA:17-item health scale, assessed participant-reported perceptions of dyspepsia; consists of 3 subscales: Pain Intensity (PI, 6-items to assess pain and intensity of abdominal discomfort; Range: 2 to 47, higher score indicates greater pain and abdominal discomfort), Non-Pain Symptoms (NPS, 7-items to assess severity and impact of non-pain symptoms: burping/belching, heartburn, bloating, flatulence, sour taste, nausea, and bad breath; Range: 7 to 35, higher scores indicate increased symptom severity and influence), and Satisfaction (4-items to assess degree of satisfaction with abdominal discomfort; Range: 2 to 23, higher scores indicate more satisfaction). Model contained treatment, visit and treatment by visit interaction as fixed effects and Baseline (predose in Study A3921030) as a covariate. A first-order autoregressive variance-covariance structure was used.

Time frame: Months 24, 36

Mean Trough Levels of Tofacitinib by Visit

The dates and times were recorded for the 6 doses of tofacitinib administered before each scheduled pharmacokinetic (PK) sampling. The participant was instructed to follow a 12 hourly schedule for these 6 doses of tofacitinib, with each dose administered within 1 hour of the scheduled time. Trough samples were collected 0 to 10 minutes prior to the morning dose. 1 hour postdose samples were required within 10 minutes of the nominal time point. Samples taken at -2 hours predose and at time points \>1 hour post dose were required within 30 minutes of the nominal time point.

Time frame: Months 18 and 24 (-2 hours, predose, 1 hour, 2 hours), Month 30 (predose, 1 hour and 2 hours), Month 36 (predose, 1, 2, and 4 hours), Months 42, 48, 54, 60, 66, 72 (predose and 2 hours)

Mean Trough Levels of Cyclosporine by Visit

All CsA samples were taken predose (collected 0 to 10 minutes prior to the morning dose).

Time frame: Predose: Months 18, 24, 36, 48, 60, 72