Protocol for treatment of lupus nephritis
By employing a pharmacodynamic dosing regimen, the effectiveness of a protocol for treatment of lupus nephritis with voclosporin can be maximized while minimizing undesirable side effects.
1. A pharmacodynamic method to treat a proteinuric kidney disease which method comprises administering to a subject diagnosed with said disease a predetermined daily dosage of an effective amounts of voclosporin over a projected treatment period of at least 24 weeks, said pharmacodynamic method further comprising:
(a) assessing the estimated Glomerular Filtration Rate (eGFR) of said subject at at least a first time point and a second time point on different days of said treatment period, and
(b) (i) if the eGFR of said subject decreases by more than a target % in the range of 20-45% to below a predetermined value in the range of 50-90 ml/min/1.73 m 2 between said first and second time points, reducing the daily dosage by increment(s) of 7.9 mg BID or stopping the administering of voclosporin to said subject;
(ii) if the eGFR of said subject decreases by less than said target % between said first and second time points, continuing administering the same predetermined daily dosage of voclosporin to said subject.
2. The method of claim 1 wherein the first time point is immediately preceding administering voclosporin.
3. The method of claim 1 wherein the predetermined value is approximately 60 ml/min/1.73 m 2 .
4. The method of claim 1 wherein the target % is approximately 30%.
5. The method of claim 1 which further includes identifying said subject as appropriate for said method prior to conducting said method on said subject by:
(a) determining that the urine protein creatinine ratio (UPCR) of said subject is >1 mg/mg as measured by first morning void or 24 hour urine; and
(b) determining said subject has an eGFR as measured by Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EP1) of >45 ml/min/1.73 m 2 ,
wherein if (a) and (b) are met, said subject is identified as appropriate for said method.
6. The method of claim 1 wherein said predetermined daily dosage is 39.5. mg voclosporin BID, 31.6 mg voclosporin BID, 23.7 mg voclosporin BID, 15.8 mg voclosporin BID or 7.9 mg voclosporin BID.
7. The method of claim 1 wherein said method further includes evaluating said subject for renal function at a time point after the end of said treatment period by assessing eGFR.
8. The method of claim 7 wherein said method further includes evaluating said subject for maintaining renal function by assessing protein/creatinine ratio (UPCR) at a time point after the end of said treatment period.
9. The method of claim 1 wherein said method further includes administering to said subject an effective amount of mycophenolate mofetil (MMF).
10. The method of claim 1 which further includes administering to said subject an effective amount of a corticosteroid.
11. The method of claim 1 wherein said treatment period is at least 48 weeks.
12. The method of claim 1 which further includes determining the eGFR of said subject at a third time point and if the eGFR is determined at said third time point to differ from the eGFR determined at said first time point by less than said target %, resuming administering said predetermined daily dosage of voclosporin.
13. The method of claim 12 wherein the target % is approximately 30%.