Basiliximab is the only available IL2-RA in the U.S., which is given as two doses of 20 mg (post-operative day 0 and 4), and costs mg unit price $3,244.57)

SUPPLEMENT:

Cost of induction agents:

In terms of cost of induction agents, Alemtuzumab offers a significant cost saving compared with r-ATG and IL2-RA based on the average whole-sale-price (Red Book Online 2014,

www.redbook.com/redbook/online), typically administered 30 mg IV once with a cost of $2,118 in 2010.

Alemtuzumab was withdrawn from the US and European markets in 2012, previously approved for chronic lymphocytic leukemia (1). Alemtuzumab was reintroduced to the US market for relapsing multiple sclerosis indication in 2014 at a higher price-point, but has been provided free to the transplant centers since 2012 (distributed only under research protocols with an IRB approval after enrolling manufacturer’s registry) (2). Basiliximab is the only available IL2-RA in the U.S., which is given as two doses of 20 mg (post-operative day 0 and 4), and costs $6,489.14 (20 mg unit price $3,244.57).

Thymoglobulin is mainly used r-ATG in the U.S. in renal transplantation, typically given 4 doses of 1.5 mg/kg (1.5 mg/kg x 70 kg x 4 doses = 420mg for a 70-kg standard adult patient) and costs $13,554.95 (unit price $797.35 per 25 mg-vial). These values are the costs of the drugs itself and do not include other related costs (cost of administration, additional hospital stay, and cost of induction related complications).

References:

1. MabCampath (alemtuzumab) withdrawal of the marketing authorisation in the European union.

http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2012/08/WC500 130945.pdf. Accessed on December 29, 2015.

2. Prescribing information for Lemtrada (alemtuzumab) at

http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/103948s5139lbl.pdf. Accessed on December 29, 2015.

Table S1. Characteristics of the recipients included in the final analysis, based on induction categories.

No induction Alemtuzumab r-ATG IL2-RA P value

N (%) 25.1 7.0 38.2 29.7

Risk groups (%) <0.001

Low risk 18.3 14.6 14.8 20.2

High risk 81.7 85.4 85.2 79.8

Donor

Age (year) 38.4±17.0 40.3±17.6 39.9±17.3 38.0±16.9 <0.001 Gender, male

(%)

58.7 57.9 59.3 59.2 0.81

AA Race, (%) 13.4 12.2 13.7 10.3 <0.001

ECD (%) 18.6 24.2 21.9 16.7 <0.001

DCD (%) 5.8 12.8 10.1 6.2 <0.001

KDRI 1.26±0.42 1.32±0.42 1.31±0.43 1.22±0.40 <0.001

KDPI (%) 46.9±28.1 51.8±27.6 50.4±27.6 44.7±27.9 <0.001

Recipient

Age (yr) 53.4±13.6 53.3±12.8 53.4±13.3 54.1±13.8 0.03

Gender, male (%)

62.2 60.2 60.0 63.6 0.002

Race, Black (%)

35.5 34.5 37.7 25.2 <0.001

BMI (%) 27.65.3 28.25.4 27.95.1 27.45.1 <0.001

DM (%) 39.7 40.1 40.1 39.4 0.90

CAD (%) 22.8 24.3 21.3 22.9 0.001

CHF (%) 12.2 11.4 10.8 11.3 0.01

PVD (%) 7.5 8.1 6.7 7.4 0.02

CVA (%) 4.4 5.0 4.0 4.2 0.14

Smoking (%) 3.7 5.5 4.0 4.5 <0.001

Dialysis time (year)

3.4±2.1 4.0±2.1 3.7±2.2 3.3±1.8 <0.001

Waiting time, (year)

2.0±1.5 2.6±1.8 2.3±1.5 2.0±1.5 <0.001

Peak PRA 12.6±25.3 14.8±27.7 15.0±28.1 9.1±21.4 <0.001

Transplant

CIT (hour) 18.4 8.7 20.89.1 18.4 8.4 18.08.0 <0.001

Pumped (%) 34.3 44.8 40.6 36.2 <0.001

HLA mm 3.71.9 3.81.8 4.01.7 3.71.9 <0.001

Discharged on CNI (%)

89.1 92.8 94.7 92.7 <0.001

Discharged on MMF (%)

81.3 90.8 89 92 <0.001

Outcomes

DGF (%) 23.4 26.3 28.7 22.4 <0.001

Acute rejection at one-year (%)

10.7 10.1 8.8 10.7 0.02

Overall graft 78.7 80.2 81.8 81.5 0.02

survival (%)

Abbreviations: IL2-RA = interleukin-2 receptor antagonist; AA = African American; ECD = expanded criteria donor;

DCD = donation after cardiac death; KDRI = kidney donor risk index; KDPI = kidney donor profile index; BMI = body mass index; DM = diabetes; CAD = coronary artery disease; CHF = congestive heart failure; PVD = peripheral vascular disease; CVA = cerebrovascular accident; PRA = panel reactive antibody; CIT = cold ischemia time; HLA = human leukocyte antigen; CNI = Calcineurin inhibitors; MMF = mycophenolate mofetil, DGF = delayed graft function.

Table S2. Multivariable Cox regression for overall allograft failure (graft failure and /or death) among deceased donor renal transplant recipients between 2000 and 2008 (study cohort).

HR P-value 95% CI

Induction

No-induction 1

Alemtuzumab 1.03 0.68 0.89-1.20

r-ATG 0.91 0.04 0.84-0.99

IL2-RA 1 0.94 0.92-1.09

HLA mismatch

0 1

1 1.23 0.08 0.98-1.55

2 1.20 0.13 0.95-1.52

3 1.18 0.13 0.95-1.47

4 1.30 0.01 1.06-1.60

5 1.26 0.03 1.03-1.55

6 1.47 <0.001 1.19-1.41

Age (years) 1.01 <0.001 1.01-1.02

Gender (male vs. female) 1.13 0.001 1.05-1.21

Race (Black vs. others) 1.18 <0.001 1.10-1.27

Diabetes 1.16 <0.001 1.08-1.25

Cardiovascular disease 1.35 <0.001 1.25-1.44

Smoking 1.22 0.004 1.07-1.41

Dialysis duration, year

0-1 1

1-3 1.25 <0.001 1.17-1.35

>3 1.78 <0.001 1.61-1.96

PRA (%) 1 0.01 1.00-1.01

KDPI (%) 1 <0.001 1.01-1.02

Cold ischemia time (hours) 1 0.13 0.99-1.00

Transplant year

2000 1

2001 0.81 0.04 0.67-0.99

2002 0.71 0.01 0.59-0.86

2003 0.67 <0.001 0.55-0.80

2004 0.60 <0.001 0.50-0.73

2005 0.57 <0.001 0.47-0.68

2006 0.48 <0.001 0.39-0.58

2007 0.41 <0.001 0.33-0.51

2008 0.16 <0.001 0.10-0.23