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The Role of Calcineurin The Role of Calcineurin Inhibitors in the Treatment Inhibitors in the Treatment of Idiopathic Membranous of Idiopathic Membranous Nephropathy Nephropathy Membranous Nephropathy Membranous Nephropathy Conference,

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SLIDE 1

The Role of Calcineurin The Role of Calcineurin Inhibitors in the Treatment Inhibitors in the Treatment

  • f Idiopathic Membranous
  • f Idiopathic Membranous

Nephropathy Nephropathy

Membranous Nephropathy Membranous Nephropathy Conference, Conference, March 30 March 30-

  • 31, 2007,

31, 2007, Bergamo, Italy Bergamo, Italy

Fernando C. Fervenza, MD Fernando C. Fervenza, MD Associate Professor of Medicine Associate Professor of Medicine Division of Nephrology and Hypertension Division of Nephrology and Hypertension Mayo Clinic College of Medicine Mayo Clinic College of Medicine Rochester, MN Rochester, MN

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SLIDE 2

Cyclosporine in Progressive MN Cyclosporine in Progressive MN

Patients Characteristics at Entry Patients Characteristics at Entry

CP1134827-25

Cattran et al: Kl 47:1130, 1995 Cattran et al: Kl 47:1130, 1995

Cyclosporine Placebo n=9 n=8 Age (range) 44 (22-59) 40 (20-61) Males (%) 8 (89) 6 (75) Creatinine (µ µ µ µmol/L) 186± ± ± ±65 204± ± ± ±81 Ccr (mL/min/1.73 m2) 51± ± ± ±20 46± ± ± ±16 Proteinuria (g/day) 11.5 (9-18) 12.8 (4-21) Serum albumin (g/L) 29± ± ± ±6.6 30± ± ± ±9.2 Systolic BP/mm Hg 141± ± ± ±6 138± ± ± ±16 Diastolic BP (mm Hg) 82± ± ± ±12 83± ± ± ±7 Ultra structural stage 2.2 (1-4) 2.0 (1-4) Interstitial fibrosis (0-4+) 0.9 (0-1) 0.4 (0-1) Tubular atrophy (0-4+) 0.7 (0-2) 0.3 (0-2) Observation period (mo) Part 1 9.3 (6-13) 9.7 (7-12) Part 2 10.1 (4-13) 8.9 (4-13) Post-med 20 (0-41) 22 (6-56) Total 49 (17-75) 48 (25-88) Cyclosporine Placebo n=9 n=8 Age (range) 44 (22-59) 40 (20-61) Males (%) 8 (89) 6 (75) Creatinine (µ µ µ µmol/L) 186± ± ± ±65 204± ± ± ±81 Ccr (mL/min/1.73 m2) 51± ± ± ±20 46± ± ± ±16 Proteinuria (g/day) 11.5 (9-18) 12.8 (4-21) Serum albumin (g/L) 29± ± ± ±6.6 30± ± ± ±9.2 Systolic BP/mm Hg 141± ± ± ±6 138± ± ± ±16 Diastolic BP (mm Hg) 82± ± ± ±12 83± ± ± ±7 Ultra structural stage 2.2 (1-4) 2.0 (1-4) Interstitial fibrosis (0-4+) 0.9 (0-1) 0.4 (0-1) Tubular atrophy (0-4+) 0.7 (0-2) 0.3 (0-2) Observation period (mo) Part 1 9.3 (6-13) 9.7 (7-12) Part 2 10.1 (4-13) 8.9 (4-13) Post-med 20 (0-41) 22 (6-56) Total 49 (17-75) 48 (25-88)

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SLIDE 3

Improvement in Rate of Change in Creatinine Clearance Improvement in Rate of Change in Creatinine Clearance

CP1134827-9

Cattran D: Curr Op Nephrol Hypert 5:427, 1996 Cattran D: Curr Op Nephrol Hypert 5:427, 1996

10 20 30 40 50 60 70 80 90 100 110

  • 15
  • 10
  • 5

5 10 15 20 25 30 35 40

Creatinine clearance (mL/min) Creatinine clearance (mL/min) Months from randomization Months from randomization Creatinine clearance (mL/min) Creatinine clearance (mL/min)

10 20 30 40 50 60 70 80 90 100 110

Cyclosporine Cyclosporine Placebo Placebo Death Dialysis Death Dialysis

  • 2.4 vs

2.4 vs -

  • 0.7

0.7

  • 2.2 vs

2.2 vs -

  • 2.1

2.1

slide-4
SLIDE 4

CP1256850-7

Cyclosporine in Progressive IMN Cyclosporine in Progressive IMN

Cyclomen Study, Follow Cyclomen Study, Follow-

  • Up 12 Months

Up 12 Months

Before Final Before Final Proteinuria 6.8±0.9 7.5±7.9 4.0±0.5 2.8±0.7 (g/24 hr) CCr 49.3±6.5 44.1±9.1 47.8±7.3 46±7.9 (mL/min/1.73 m2) Before Final Before Final Proteinuria 6.8±0.9 7.5±7.9 4.0±0.5 2.8±0.7 (g/24 hr) CCr 49.3±6.5 44.1±9.1 47.8±7.3 46±7.9 (mL/min/1.73 m2)

Pisoni et al: JASN, 2000 (abstract) Pisoni et al: JASN, 2000 (abstract)

Remissions 2 4 ESRD 3 1 Remissions 2 4 ESRD 3 1 CsA n=10 CsA n=10 Conservative n=11 Conservative n=11

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SLIDE 5

Cyclosporine in Steroid Cyclosporine in Steroid-

  • Resistant MN

Resistant MN

Baseline Demographic and Laboratory Data Baseline Demographic and Laboratory Data

  • f 51 Randomized Patients
  • f 51 Randomized Patients

CP1134827-26

Data ± ± ± ± SD Cattran et al: Kl 59:1484, 2001 Data ± ± ± ± SD Cattran et al: Kl 59:1484, 2001 Placebo Cyclosporine Initial n=23 n=28 Age range 49± ± ± ±14 47± ± ± ±11 Gender (M:F) 16/7 26/2 Blood pressure (mm Hg) Systolic 138± ± ± ±16 137± ± ± ±18 Diastolic 84± ± ± ±9 84± ± ± ±7 Racial group, No. (%) Caucasians 20 (87) 24 (86) African-American 0 (0) 1 (4) Other/mixed 3 (13) 2 (10) Serum albumin (g/dL) 2.7± ± ± ±0.6 2.8± ± ± ±0.6 Serum creatinine (mg/dL) 1.1± ± ± ±0.3 1.3± ± ± ±0.5 Creatinine clearance 95± ± ± ±37 90± ± ± ±27 (mL/min/1.73 m2) Proteinuria (g/day) 8.8± ± ± ±4.7 9.7± ± ± ±5.3 Urine urea (g/day) 9.5± ± ± ±3.6 10.3± ± ± ±4.0 Placebo Cyclosporine Initial n=23 n=28 Age range 49± ± ± ±14 47± ± ± ±11 Gender (M:F) 16/7 26/2 Blood pressure (mm Hg) Systolic 138± ± ± ±16 137± ± ± ±18 Diastolic 84± ± ± ±9 84± ± ± ±7 Racial group, No. (%) Caucasians 20 (87) 24 (86) African-American 0 (0) 1 (4) Other/mixed 3 (13) 2 (10) Serum albumin (g/dL) 2.7± ± ± ±0.6 2.8± ± ± ±0.6 Serum creatinine (mg/dL) 1.1± ± ± ±0.3 1.3± ± ± ±0.5 Creatinine clearance 95± ± ± ±37 90± ± ± ±27 (mL/min/1.73 m2) Proteinuria (g/day) 8.8± ± ± ±4.7 9.7± ± ± ±5.3 Urine urea (g/day) 9.5± ± ± ±3.6 10.3± ± ± ±4.0

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SLIDE 6

Cyclosporine in MGN Cyclosporine in MGN

CP1134827-24

Cattran et al: Kidney Int 59:1484, 2001 Cattran et al: Kidney Int 59:1484, 2001

Weeks Weeks

78 52 26

Cyclosporine Cyclosporine Placebo Placebo

28 28 2 CR 2 CR 19 PR 19 PR 7 NR 7 NR 7 NR 7 NR 2 CR 2 CR 2 CR 2 CR 11 PR 11 PR 8 R 8 R 9 PR 9 PR 10 R 10 R

(1) (1) (1) (1) (1) (1) (8) (8) (2) (2) (8) (8) (1) (1) (2) (2) (1) (1)

1 CR 1 CR 2 PR 2 PR 3 R 3 R 17 NR 17 NR 18 NR 18 NR 2 R 2 R 2 PR 2 PR 1 CR 1 CR 1 CR 1 CR 4 PR 4 PR 18 NR 18 NR 23 23

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SLIDE 7

CyA Treatment in Membranous Nephropathy CyA Treatment in Membranous Nephropathy

CP1123327-6

Rate of complete remission (%) Rate of complete remission (%) Duration of treatment (months) Duration of treatment (months)

MC MGN Censored MC MGN Censored

20 40 60 80 100 6 12 18 24

Merier, NDT 14: 1036, 1999 Merier, NDT 14: 1036, 1999

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SLIDE 8

CP1256850-14

Induction and long Induction and long-

  • term treatment

term treatment Initial Treatment Initial Treatment

I) Treatment groups

  • Pred + CsA

31 patients

  • CsA alone

20 patients II) Treatment regimen

  • Pred 0.6 mg/kg/day with tapering
  • CsA 2-3 mg/kg/day

Target whole blood 12-hour trough levels 100-200 ng/mL III) Duration of treatment

  • 12 months

I) Treatment groups

  • Pred + CsA

31 patients

  • CsA alone

20 patients II) Treatment regimen

  • Pred 0.6 mg/kg/day with tapering
  • CsA 2-3 mg/kg/day

Target whole blood 12-hour trough levels 100-200 ng/mL III) Duration of treatment

  • 12 months

Alexopoulos Alexopoulos et al. NDT 21: 3127 et al. NDT 21: 3127-

  • 3132, 2006

3132, 2006

slide-9
SLIDE 9

CP1256850-15

Outcome Outcome

5 80 20 65 19 64 35 48

20 40 60 80 100 Complete Partial Complete Partial

Response of proteinuria (% of patients) Response of proteinuria (% of patients)

6 Months 6 Months 12 Months 12 Months

Alexopoulos et al. NDT 21: 3127-3132, 2006 Alexopoulos Alexopoulos et al. NDT 21: 3127 et al. NDT 21: 3127-

  • 3132, 2006

3132, 2006 CsA Pred+CsA CsA Pred+CsA

No relapses No relapses

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SLIDE 10

CP1256850-18

Long Term Treatment of IMN Long Term Treatment of IMN

I) Treatment groups

  • Pred + CsA

26 patients (11 CR, 15 PR)

  • CsA alone

17 patients (4 CR, 13 PR) II) Treatment regimen

  • Pred

~0.1 mg/kg/day

  • CsA

~1.5/kg/day over 2 months I) Treatment groups

  • Pred + CsA

26 patients (11 CR, 15 PR)

  • CsA alone

17 patients (4 CR, 13 PR) II) Treatment regimen

  • Pred

~0.1 mg/kg/day

  • CsA

~1.5/kg/day over 2 months

Alexopoulos et al. NDT 21: 3127-3132, 2006 Alexopoulos Alexopoulos et al. NDT 21: 3127 et al. NDT 21: 3127-

  • 3132, 2006

3132, 2006

Proteinuria (g/24 hr) 1.1±1.7 1.1±0.8 CsA dose (mg/day) 105±25 (P+C) 111±40 (C) Follow-up (months) 26±16 18±7

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SLIDE 11

CP1256850-20

Pred + CsA vs CsA in IMN Pred + CsA vs CsA in IMN

Long Long-

  • Term Treatment

Term Treatment

Pred + CsA CsA P Relapses (no.) 4/26 (15%) 8/17 (47%) <0.05 Time to relapse 10±2 6±4 NS (months) Pred + CsA CsA P Relapses (no.) 4/26 (15%) 8/17 (47%) <0.05 Time to relapse 10±2 6±4 NS (months)

Alexopoulos et al. NDT 21: 3127-3132, 2006 Alexopoulos Alexopoulos et al. NDT 21: 3127 et al. NDT 21: 3127-

  • 3132, 2006

3132, 2006

*≥ ≥ ≥ ≥ 50% increase in proteinuria *≥ ≥ ≥ ≥ 50% increase in proteinuria

Relapsers Non relapsers P I) CsA dose (mg/kg) Pred + CsA 1.0±0.3 1.4±0.5 <0.001 CsA 1.1±0.2 1.5±0.4 <0.003 II) CsA levels (Co) 72±48 194±80 <0.03 (ng/mL)

slide-12
SLIDE 12

CP1256850-22

Final Outcome Final Outcome

End of End of Remission 12 months follow-up 12 months follow-up Complete 11 10 4 4 Partial 15 16 13 13 SCr (mg/dL) 1.3±0.6 1.3±0.4 1.1±0.3 1.1±0.2 Proteinuria 1.1±1.7 1.0±1.4 1.1±0.8 1.0±0.7 (g/24 hr) End of End of Remission 12 months follow-up 12 months follow-up Complete 11 10 4 4 Partial 15 16 13 13 SCr (mg/dL) 1.3±0.6 1.3±0.4 1.1±0.3 1.1±0.2 Proteinuria 1.1±1.7 1.0±1.4 1.1±0.8 1.0±0.7 (g/24 hr) Pred+CsA n=26 Pred+CsA n=26 CsA N=17 CsA N=17

Relapses treated by Relapses treated by CsA dose; in 2 patients CsA dose; in 2 patients prednisone dose prednisone dose Response = to initial treatment Response = to initial treatment

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SLIDE 13

Tacrolimus Monotherapy Tacrolimus Monotherapy Protein Excretion Protein Excretion

2000 4000 6000 8000 10000 12000 14000 16000 18000 20000

Entry Six Months Nine Months Fifteen Months

Time Point Proteinuria (mg)

9097 ± 3566 g/day

5291 ± 5979 g/day

3407 ± 2046 g/day 2872 ± 1942 g/day

Amer Amer et al. ASN 2006 (abs) et al. ASN 2006 (abs)

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SLIDE 14

CP1262145-6

5,000 10,000 15,000 56.0 67.0 78.0 89.0 100.0

mg/24 hr mg/24 hr mL/min/SA mL/min/SA

31 Dec 04 31 Dec 05 31 Dec 06

Total protein Total protein Creatinine clearance Creatinine clearance

Amer Amer et al. ASN 2006 (abs) et al. ASN 2006 (abs)

slide-15
SLIDE 15

CP1262145-5

5,000 10,000 15,000 20,000 0.0 50.0 100.0 150.0

mg/24 hr mg/24 hr mL/min/SA mL/min/SA

31 Dec 04 31 Dec 05 31 Dec 06

Total protein Total protein Creatinine clearance Creatinine clearance

Amer Amer et al. ASN 2006 (abs) et al. ASN 2006 (abs)

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SLIDE 16

Tacrolimus monotherapy Tacrolimus monotherapy randomized controlled trial randomized controlled trial

0.05 mg/kg/day for 12 months; 6 months taper 0.05 mg/kg/day for 12 months; 6 months taper

Praga Praga et al. Kidney Int. 2007 (in press) et al. Kidney Int. 2007 (in press)

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SLIDE 17

Tacrolimus monotherapy Tacrolimus monotherapy Randomized controlled trial Randomized controlled trial

Praga Praga et al. Kidney Int. 2007 (in press) et al. Kidney Int. 2007 (in press)

72% 72% 22% 22% 76% 76% 30% 30%

slide-18
SLIDE 18

CP1256850-23

Conclusions Conclusions

  • Both Cyclosporine (± steroids) and Tacrolimus are

effective for inducing remission in most NS patients with IMN and normal or near normal renal function

  • Both are well tolerated
  • Prolonged treatment is needed in order to achieve

maximal success

  • Lower doses (CsA 1.4-1.5 mg/kg/day; TAC 0.05

mg/kg/day) are useful and may be safe for maintenance

  • f remission provided.
  • Relapses are more frequent in the monotherapy group,

when dose is lower (1.0-1.1 mg/kg) or when CsA levels are below 100 mg/mL

  • Both Cyclosporine (± steroids) and Tacrolimus are

effective for inducing remission in most NS patients with IMN and normal or near normal renal function

  • Both are well tolerated
  • Prolonged treatment is needed in order to achieve

maximal success

  • Lower doses (CsA 1.4-1.5 mg/kg/day; TAC 0.05

mg/kg/day) are useful and may be safe for maintenance

  • f remission provided.
  • Relapses are more frequent in the monotherapy group,

when dose is lower (1.0-1.1 mg/kg) or when CsA levels are below 100 mg/mL

slide-19
SLIDE 19
slide-20
SLIDE 20

CP1256850-8

Cyclosporine in IMN Cyclosporine in IMN

Responders vs Responders vs Nonresponders Nonresponders

Responders Nonresponders P Age (yr) 40±9 55±10 <0.01 Scr (mg/dL) 1.1±0.4 2.1±0.8 <0.005 Proteinuria (g/24 hr) 5.6±3.3 4.8±3.5 NS Segmental scars (%) 15% 33% <0.005 Obsolete glom (%)* 7% 28% <0.01 TIN fibrosis* 18% 52% <0.005 Responders Nonresponders P Age (yr) 40±9 55±10 <0.01 Scr (mg/dL) 1.1±0.4 2.1±0.8 <0.005 Proteinuria (g/24 hr) 5.6±3.3 4.8±3.5 NS Segmental scars (%) 15% 33% <0.005 Obsolete glom (%)* 7% 28% <0.01 TIN fibrosis* 18% 52% <0.005

Alexopoulos et al: Nephrology, 2002 Alexopoulos et al: Nephrology, 2002 *Important also in multivariate analysis *Important also in multivariate analysis

slide-21
SLIDE 21

CP1256850-16

Outcome of Renal Function Outcome of Renal Function

Initial Treatment, 12 Months Initial Treatment, 12 Months

Pred + CsA CsA Pre 5.1±2.5 4.9±1.5 Proteinuria <0.0001 <0.0001 (g/24 hr) Post 1.1±2.7 1.1±0.8 Pre 1.2±0.4 1.0±0.2 Creatinine NS NS (mg/dL) Post 1.3±0.6 1.1±0.3 Relapses Pred + CsA CsA Pre 5.1±2.5 4.9±1.5 Proteinuria <0.0001 <0.0001 (g/24 hr) Post 1.1±2.7 1.1±0.8 Pre 1.2±0.4 1.0±0.2 Creatinine NS NS (mg/dL) Post 1.3±0.6 1.1±0.3 Relapses Alexopoulos et al. NDT 21: 3127-3132, 2006 Alexopoulos Alexopoulos et al. NDT 21: 3127 et al. NDT 21: 3127-

  • 3132, 2006

3132, 2006

slide-22
SLIDE 22

CP1256850-17

No. % No. % No. % Hypertension 8 25 4 20 12 23 (new/aggravated) Increase in Scr 8 25 5 25 13 25 No. % No. % No. % Hypertension 8 25 4 20 12 23 (new/aggravated) Increase in Scr 8 25 5 25 13 25 Pred + CsA Pred + CsA CsA CsA Total Total

Alexopoulos Alexopoulos et al. NDT 21: 3127 et al. NDT 21: 3127-

  • 3132, 2006

3132, 2006

Pred + CsA CsA Pre 5.1±2.5 4.9±1.5 Proteinuria <0.0001 <0.0001 (g/24 hr) Post 1.1±2.7 1.1±0.8 Pre 1.2±0.4 1.0±0.2 Creatinine NS NS (mg/dL) Post 1.3±0.6 1.1±0.3 Relapses Pred + CsA CsA Pre 5.1±2.5 4.9±1.5 Proteinuria <0.0001 <0.0001 (g/24 hr) Post 1.1±2.7 1.1±0.8 Pre 1.2±0.4 1.0±0.2 Creatinine NS NS (mg/dL) Post 1.3±0.6 1.1±0.3 Relapses

slide-23
SLIDE 23

CP1256850-11

Relapses of Proteinuria After CSA Treatment Relapses of Proteinuria After CSA Treatment

Relapse CyA dose Duration of CsA rate (mg/kg) treatment (mo) (%) Zietse et al, 1989 4-5 3 100 Guasch et al, 1992 4-6 3 78 Cattran et al, 2001 3.5 6 43 Rostoker et al, 1993 4.5 15 30 Relapse CyA dose Duration of CsA rate (mg/kg) treatment (mo) (%) Zietse et al, 1989 4-5 3 100 Guasch et al, 1992 4-6 3 78 Cattran et al, 2001 3.5 6 43 Rostoker et al, 1993 4.5 15 30

slide-24
SLIDE 24

CP1256850-21

Relapses and CsA Dose/Levels Relapses and CsA Dose/Levels

Relapsers Non relapsers P I) CsA dose (mg/kg) Pred + CsA 1.0±0.3 1.4±0.5 <0.001 CsA 1.1±0.2 1.5±0.4 <0.003 II) CsA levels (Co) 72±48 194±80 <0.03 (ng/mL) Relapsers Non relapsers P I) CsA dose (mg/kg) Pred + CsA 1.0±0.3 1.4±0.5 <0.001 CsA 1.1±0.2 1.5±0.4 <0.003 II) CsA levels (Co) 72±48 194±80 <0.03 (ng/mL)

Alexopoulos et al. NDT 21: 3127-3132, 2006 Alexopoulos Alexopoulos et al. NDT 21: 3127 et al. NDT 21: 3127-

  • 3132, 2006

3132, 2006

slide-25
SLIDE 25

Measured Creatinine Clearance Measured Creatinine Clearance

20 40 60 80 100 120 140 160 180 Entry 6 Months 9 Months 15 Months Time Point Cr Cl ml/min/SA

83 ± 17 84 ± 32 76 ± 20 81 ± 28

slide-26
SLIDE 26

p 0.95 p 0.0.19

slide-27
SLIDE 27

Summary Summary

  • Treatment with Tacrolimus was associated

Treatment with Tacrolimus was associated with a significant drop in proteinuria. with a significant drop in proteinuria.

  • At final follow up:

At final follow up:

  • One patient achieved complete

One patient achieved complete remission remission

  • Five had sub

Five had sub-

  • nephrotic range

nephrotic range proteinuria proteinuria

  • Four continued to suffer from nephrotic

Four continued to suffer from nephrotic range proteinuria range proteinuria

  • It is possible that complete remission may

It is possible that complete remission may be achieved with longer periods of therapy be achieved with longer periods of therapy

slide-28
SLIDE 28

CP1256850-10

CSA treatment for nephrotic syndrome in MN: CSA treatment for nephrotic syndrome in MN:

  • utcome in prospective studies correlated to duration of
  • utcome in prospective studies correlated to duration of

treatment treatment

Duration of CR PR R treatment (mo) (%) (%) (%) Guasch et al, 1992 3 71 78 Zietse et al, 1992 3 NA 100 Cattran et al, 2001 6 7 68 43 De Santo et al. > 6 4/5 (80%) Alexopoulos et al, 2000 11 25 60 Fritsche et al, 1999 12 34 NA Rostoker et al, 1993 15 27 46 30 Duration of CR PR R treatment (mo) (%) (%) (%) Guasch et al, 1992 3 71 78 Zietse et al, 1992 3 NA 100 Cattran et al, 2001 6 7 68 43 De Santo et al. > 6 4/5 (80%) Alexopoulos et al, 2000 11 25 60 Fritsche et al, 1999 12 34 NA Rostoker et al, 1993 15 27 46 30

NA: not available NA: not available

slide-29
SLIDE 29

70 80 90 100 110 120 130 2 4 6 8 10 12 14 16

CP1151810-40

Low Low-

  • Dose CSA May Reduce Nephrotoxicity

Dose CSA May Reduce Nephrotoxicity

41 Uveitis Patients 41 Uveitis Patients

Bagnis et al: JASN, 2002 Bagnis et al: JASN, 2002

Years Years Serum creatinine (mol/L) Serum creatinine (mol/L)

P<0.003 P<0.003 CSA >3 mg/kg/d CSA >3 mg/kg/d CSA ≤ ≤ ≤ ≤3 mg/kg/d CSA ≤ ≤ ≤ ≤3 mg/kg/d

n=28 n=28 n=13 n=13

slide-30
SLIDE 30

CP1256850-19

Long Long-

  • Term Treatment with CsA

Term Treatment with CsA

Pred+CsA CsA n=26 n=17 Proteinuria (g/24 hr) 1.1±1.7 1.1±0.8 Scr (mg/dL) 1.3±0.6 1.1±0.3 CsA dose (mg/kg) 1.3±0.4 1.4±0.5 CsA dose (mg/day) 105±25 111±40 Follow-up (months) 26±16 18±7 Pred+CsA CsA n=26 n=17 Proteinuria (g/24 hr) 1.1±1.7 1.1±0.8 Scr (mg/dL) 1.3±0.6 1.1±0.3 CsA dose (mg/kg) 1.3±0.4 1.4±0.5 CsA dose (mg/day) 105±25 111±40 Follow-up (months) 26±16 18±7

Alexopoulos et al. NDT 21: 3127-3132, 2006 Alexopoulos Alexopoulos et al. NDT 21: 3127 et al. NDT 21: 3127-

  • 3132, 2006

3132, 2006

slide-31
SLIDE 31

CP1256850-24

Calcineurin Inhibitors in IMN Calcineurin Inhibitors in IMN

Guidelines and Algorithm Guidelines and Algorithm

Who to treat

  • Medium- and high-risk patients with the NS
  • Treat for a minimum of 6 months

Targets of treatment

  • CR or PR
  • Maintenance of GFR vs Reduction in Proteinuria
  • Co=125-200 ng/mL, C2=400-600 ng/mL

When to stop treatment

  • If no reduction by 50% of proteinuria by the end of

6 months therapy

  • If CR occurs taper off over 3-4 months
  • If PR occurs continue for 1-2 years and then taper gradually

Who to treat

  • Medium- and high-risk patients with the NS
  • Treat for a minimum of 6 months

Targets of treatment

  • CR or PR
  • Maintenance of GFR vs Reduction in Proteinuria
  • Co=125-200 ng/mL, C2=400-600 ng/mL

When to stop treatment

  • If no reduction by 50% of proteinuria by the end of

6 months therapy

  • If CR occurs taper off over 3-4 months
  • If PR occurs continue for 1-2 years and then taper gradually