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

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.

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

Population: Safety Analysis Set. n is the number of participants remaining at risk at each visit.

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.

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

Population: FAS. n is the number of participants remaining at risk at each visit.

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.

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

Population: FAS. n is the number of participants remaining at risk at each visit.

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.

Time frame: Month 36

Population: Full analysis set (FAS, which was defined the same as the Safety Analysis Set). The analysis included 1 participant in CsA and 2 in Tofacitinib LI from before protocol Amendment 1. Only subjects at Month 36 with GFR calculations were included.

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

Time frame: Months 12 through 72.

Population: Safety Analysis Set. Percentages use n (the number of participants with malignancies: 7,8,8 respectively) and include 1 participant in CsA and 2 in Tofacitinib LI from before dose reduction to 5 mg by Month 18 was implemented (protocol Amendment 1)

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.

Time frame: Month 36

Population: FAS. Only participants with Banff CS values at both Day 0 and Month 36 visits were included.

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

Population: FAS. n is the number of participants remaining at risk at each 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

Population: FAS. n is the number of participants remaining at risk at each 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

Population: FAS. n is the number of participants remaining at risk at each 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

Population: FAS. n is the number of participants remaining at risk at each 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

Population: Safety Analysis Set. n is the number of participants with the assessment at each visit.

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

Population: Safety Analysis Set. n is the number of participants with the assessment at each 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

Population: Safety Analysis Set. n is the number of participants with the assessment at each 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

Population: Safety Analysis Set.

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

Population: Safety Population. n is the number of participants with the assessment at each visit.

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

Population: Safety Analysis Set. n is the number of participants with the assessment at each visit.

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

Population: Safety Analysis Set. n is the number of participants with the assessment at each 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

Population: Safety Analysis Set. n is the number of participants with the assessment at each 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

Population: Safety Analysis Set. n is the number of participants with the assessment at each 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

Population: Safety Analysis Set. n is the number of participants with the assessment at each 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

Population: Safety Population. n is the number of participants with the assessment at each 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

Population: Safety Analysis Set. n is the number of participants with the assessment at each visit.