Table A: Average Costs Per Patient (12 Months, 10 Years, Sensitivity Analysis 1)

Cost-effectiveness of modern mTOR inhibitor based immunosuppression compared to the standard of care after renal transplantation in Germany

Supplementary material

Sensitivity Analyses

Table A: Average costs per patient (12 months, 10 years, sensitivity analysis 1). Average costs per patient Average costs per patient

(EUR, 12 months) (EUR, 10 years)

TR 1: Sirolimus+early withdrawal of Cyclosporine 26,310 146,078 +steroids

TR 2: Sirolimus-early-transition 19,424 116,153

TR 3: Everolimus-early-transition 24,925 155,524

TR 4: Tacrolimus low dose+MMF+steroids 18,538 126,779

EUR: Euro, TR: Therapy Regimen

Table B: Results of the MTC analysis (annual event probabilities for year 1, sensitivity analysis 2) Event Therapy regimen

1 2 3 4

15.70 1.90 0.09 3.30 Death (all causes) (0.1-82.8) (0-11.3) (0-0.1) (0.1-20.9)

8.00 5.40 32.30 3.20 Graft failure (0.2-46.0) (0.3-25.5 (0.0-100) (0.1-16.2)

6.37 4.58 8.59 12.81 Malignancies (total) (0.0-55.9) (0.1-25.7) (0.1-51.6) (0.2-66.9)

24.72 18.77 30.10 27.48 Post-transplant hypertension treatment (probability per year) (0.4-89.4) (0.9-66.1) (1.3-87.3) (1.2-84.7)

Probabilities (%) for 1 year with initial immunosuppressive regimen; credibility intervals presented in parentheses Table C: Outcomes for 12 months simulation (average costs, LYs, and years with FG per patient, sensitivity analysis 2). Average years Average cost per Average LY per with FG per patient (EUR) patient patient

TR 1: Sirolimus+early withdrawal of 25,607 0.925 0.892 Cyclosporine +steroids

TR 2: Sirolimus-early-transition 17,488 0.990 0.967

TR 3: Everolimus-early-transition 31,226 0.958 0.814

TR 4: Tacrolimus low dose+MMF+steroids 16,264 0.984 0.971 TR: Therapy Regimen; LY: Life Years; FG: Functioning Graft

Table D: ICER in Euro per LY gained for 12 months (sensitivity analysis 2). TR 1: TR 4: Tacrolimus Sirolimus+early TR 2: Sirolimus- TR 3: Everolimus- low withdrawal of early-transition vs. early-transition vs. dose+MMF+steroid Cyclosporine s vs. +steroids vs.

TR 1: Sirolimus+early Dominates Dominates withdrawal of N.A. N.E. Cyclosporine +steroids (+) (+)

Dominated Dominated TR 2: Sirolimus-early- N.A. N.E. transition (−) (−)

Dominates Dominates TR 3: Everolimus-early- 170,273 N.A. transition (+) (+)

Dominated Dominated TR 4: Tacrolimus low 204,000 N.A. dose+MMF+steroids (−) (−) Note: ICERs/dominance for therapy regimen in the top row versus therapy regimen in the left column. (+) indicates a domination of the therapy regimen in the top row versus therapy regimen in the left column. (−) indicates a domination of the therapy regimen in the left column versus therapy regimen top row. N.A.: ICER calculation not possible; N.E.: lower effects at lower costs, no ICER derived TR: Therapy Regimen; LY: Life Years

Table E: ICER in Euro per year with FG gained for 12 months (sensitivity analysis 2). TR 1: TR 4: Tacrolimus Sirolimus+early TR 2: Sirolimus- TR 3: Everolimus- low withdrawal of early-transition vs. early-transition vs. dose+MMF+steroid Cyclosporine s vs. +steroids vs.

TR 1: Sirolimus+early Dominates Dominated Dominates withdrawal of N.A. Cyclosporine +steroids (+) (−) (+)

Dominated Dominated Dominates TR 2: Sirolimus-early- N.A. transition (−) (−) (+)

Dominates Dominates Dominates TR 3: Everolimus-early- N.A. transition (+) (+) (+)

Dominated Dominated Dominated TR 4: Tacrolimus low N.A. dose+MMF+steroids (−) (−) (−) Note: ICERs/dominance for therapy regimen in the top row versus therapy regimen in the left column. (+) indicates a domination of the therapy regimen in the top row versus therapy regimen in the left column. (−) indicates a domination of the therapy regimen in the left column versus therapy regimen top row. N.A.: ICER calculation not possible; N.E.: lower effects at lower costs, no ICER derived TR: Therapy Regimen; LY: Life Years

Table F: Outcomes for 10 years simulation (average costs, LYs, and years with FG per patient, sensitivity analysis 2). Average years Average cost per Average LY per with FG per patient (EUR) patient patient

TR 1: Sirolimus+early withdrawal of 144,763 5.626 5.003 Cyclosporine +steroids

TR 2: Sirolimus-early-transition 108,048 6.509 5.857

TR 3: Everolimus-early-transition 160,569 5.464 4.185

TR 4: Tacrolimus low dose+MMF+steroids 114,457 6.495 5.915 TR: Therapy Regimen; LY: Life Years; FG: Functioning Graft

Table G: ICER in Euro per LY gained for 10 years (sensitivity analysis 2). TR 1: TR 4: Tacrolimus Sirolimus+early TR 2: Sirolimus- TR 3: Everolimus- low withdrawal of early-transition vs. early-transition vs. dose+MMF+steroid Cyclosporine s vs. +steroids vs.

Dominated Dominated Dominated TR 2: Sirolimus-early- N.A. transition (−) (−) (-)

Dominated Dominates Dominated TR 4: Tacrolimus low N.A. dose+MMF+steroids (−) (+) (−)

Note: ICERs/dominance for therapy regimen in the top row versus therapy regimen in the left column. (+) indicates a domination of the therapy regimen in the top row versus therapy regimen in the left column. (−) indicates a domination of the therapy regimen in the left column versus therapy regimen top row. N.A.: ICER calculation not possible; N.E.: lower effects at lower costs, no ICER derived TR: Therapy Regimen; LY: Life Years

Table H: ICER in Euro per year with FG gained for 10 years (sensitivity analysis 2). TR 1: TR 4: Tacrolimus Sirolimus+early TR 2: Sirolimus- TR 3: Everolimus- low withdrawal of early-transition vs. early-transition vs. dose+MMF+steroid Cyclosporine s vs. +steroids vs.

Dominated Dominated TR 2: Sirolimus-early- N.A. 110,500 transition (−) (−)

Dominated Dominated TR 4: Tacrolimus low N.E. N.A. dose+MMF+steroids (−) (−)

Note: ICERs/dominance for therapy regimen in the top row versus therapy regimen in the left column. (+) indicates a domination of the therapy regimen in the top row versus therapy regimen in the left column. (−) indicates a domination of the therapy regimen in the left column versus therapy regimen top row. N.A.: ICER calculation not possible; N.E.: lower effects at lower costs, no ICER derived TR: Therapy Regimen; LY: Life Years Table I : Average costs per patient (12 months, 10 years). Average costs per patient Average costs per patient

(12 months) (10 years)

lower value base case upper value lower value base case upper value

± 50% change in drug costs

(incl. co-med.)

TR 1: Sirolimus+early withdrawal of Cyclosporine 16,003 26,011 36,020 96,276 145,788 196,256 +steroids

TR 2: Sirolimus-early- 11,016 17,500 23,915 75,948 107,246 139,302 transition

TR 3: Everolimus-early- 16,238 24,225 32,212 105,181 154,822 206,403 transition

TR 4: Tacrolimus low 9,970 16,404 22,838 80,437 114,612 150,517 dose+MMF+steroids

± 50% change in costs of

dialysis

± 50% change in costs of acute rejection and graft failure

TR: Therapy Regimen Table J: ICERs affected by a ±20% of the probability for acute rejection (sensitivity analysis 4) lower value base case upper value

TR 2: Sirolimus-early-transition vs. TR 4: Tacrolimus low dose+MMF+steroids (12 months)

ICER in Euro per LY gained 466,000 548,000 620,500

TR 3: Everolimus-early-transition vs. TR 1: Sirolimus+early withdrawal of Cyclosporine +steroids (10 years)

ICER in Euro per year with FG gained 40,929 45,626 N.A.

TR 4: Tacrolimus low dose+MMF+steroids vs. TR 2: Sirolimus-early-transition (10 years)

ICER in Euro per LY gained N.A. 387,684 453,706

TR: Therapy Regimen; N.A.: Use of lower/upper values from sensitivity analysis does not affect the lower/upper value of the simulation results

Table K: ICERs affected by a ±20% of the probability for graft failure (sensitivity analysis 5) lower value base case upper value

TR 2: Sirolimus-early-transition vs. TR 4: Tacrolimus low dose+MMF+steroids (12 months)

TR 3: Everolimus-early-transition vs. TR 1: Sirolimus+early withdrawal of Cyclosporine +steroids (10 years)

ICER in Euro per LY gained N.A. 26,571 26,841

TR 4: Tacrolimus low dose+MMF+steroids vs. TR 2: Sirolimus-early-transition (10 years)

ICER in Euro per year with FG gained 88,011 102,306 124,466

TR: Therapy Regimen; N.A.: Use of lower/upper values from sensitivity analysis does not affect the lower/upper value of the simulation results

Table L: SHI costs (generic) on mg basis (Lauer-Fischer (2012). WEBAPO® LAUER-Taxe (Stand 29.03.2012)) SHI- SHI- Pharmacies SHI- Mandatory Patients' Co- relevant Units per mg per relevant Active agent Brand considered Marketed by ' Retail Pack size relevant discount Payment price per package unit cost per Price (AVP) cost per mg pack unit Pfizer RAPAMUNE Sirolimus Pharma 1,868.40 € 236.48 € 10.00 € 1,621.92 € N3 100 2 16.22 € 8.11 € 2 mg Tabletten GmbH Novartis CERTICAN Everolimus Pharma 1,611.84 € 355.80 € 10.00 € 1,246.04 € N3 100 1 12.46 € 12.46 € 1 mg Tabletten GmbH

TACROLIMUS Hexal Tacrolimus Hexal Pharma 1,724.86 € 81.65 € 10.00 € 1,633.21 € N3 100 5 16.33 € 3.27 € 5 mg Kapseln

CICLOSPORIN 100 1A Pharma Cyclosporine 355.18 € 0.00 € 0.00 € 355.18 € N3 100 100 3.55 € 0.0355 € 1A Pharma Kapseln Pharma

MYCOPHENOLAT 1A Pharma MMF 1A Pharma 500 mg 527.99 € 65.49 € 10.00 € 452.50 € N3 250 500 1.81 € 0.0036 € Pharma Filmtabletten

MYFORTIC 180 mg Novartis EC-MPS magensaftresis- Pharma 198.06 € 33.70 € 10.00 € 154.36 € N2 100 180 1.54 € 0.0086 € tente Tabletten GmbH PREDNISOLON acis Prednisolon ACIS 20 mg Arzneimittel 20.11 € 0.00 € 5.00 € 15.11 € N3 100 20 0.15 € 0.0076 € Tabletten GmbH