Inpharma 1242 - 17 Jun 2000 Successful islet cell transplantation without corticosteroids Successful islet cell transplantation and subsequent independence from exogenous insulin may be achieved in patients with type 1 diabetes mellitus with the use of an immunosuppressant regimen which does not include corticosteroids, report researchers from Canada. This study involved 7 consecutive patients with type 1 diabetes who had severe hypoglycaemia or whose diabetes remained uncontrolled despite their compliance with an insulin treatment regimen. Patients received an immunosuppressant regimen comprising sirolimus [‘Rapamune’], tacrolimus [‘Prograf’] and daclizumab [‘Zenapax’], starting immediately before undergoing islet cell transplantation. * The median duration of follow-up at the time of the report was 11.9 months. Once a sufficient number of islet cells were transplanted, all patients became independent of exogenous insulin and had no further episodes of severe hypoglycaemia. ** Significant reductions from baseline in mean glycosylated haemoglobin levels were seen at 3 and 6 months (from 8.4% at baseline to 5.7% at both 3 and 6 months). Patients also had significant reductions from baseline in mean 24-hour blood glucose levels and the mean amplitude of glycaemic excursions. Serum C-peptide levels increased significantly from baseline. The researchers suggest that the immunosuppressant regimen used, in addition to protecting against autoimmune and alloimmune reactivity, ‘minimized the possibility of damaging beta cells and increasing insulin resistance’. * Patients received oral sirolimus 0.2 mg/kg (loading dose) then 0.1 mg/kg/day (adjusted to maintain concentrations of 12–15 ng/ml for the first 3 months and concentrations of 7–10 ng/ml thereafter), oral tacrolimus at an initial dosage of 1mg twice daily (subsequently adjusted to maintain a trough concentration of 3–6 ng/ml) and IV daclizumab 1 mg/kg every 14 days for a total of 5 doses. Patients undergoing a second transplantation procedure > 10 weeks after the first received an additional course of daclizumab. ** Six patients required 2 transplantation procedures while the remaining patient required 3 procedures. Shapiro AMJ, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. New England Journal of Medicine 343: 230-238, 27 Jul 2000 800820658 » Editorial comment: The above-mentioned study has been released by the NEJM via the Internet before its publication date, due to its potential therapeutic implications. A final version of the study report will be published in the 27 July 2000 issue of the NEJM. 1 Inpharma 17 Jun 2000 No. 1242 1173-8324/10/1242-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved

Successful islet cell transplantation without corticosteroids

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Inpharma 1242 - 17 Jun 2000

Successful islet celltransplantation without

corticosteroidsSuccessful islet cell transplantation and subsequent

independence from exogenous insulin may be achievedin patients with type 1 diabetes mellitus with the use ofan immunosuppressant regimen which does not includecorticosteroids, report researchers from Canada.

This study involved 7 consecutive patients with type 1diabetes who had severe hypoglycaemia or whosediabetes remained uncontrolled despite theircompliance with an insulin treatment regimen. Patientsreceived an immunosuppressant regimen comprisingsirolimus [‘Rapamune’], tacrolimus [‘Prograf’] anddaclizumab [‘Zenapax’], starting immediately beforeundergoing islet cell transplantation.* The medianduration of follow-up at the time of the report was 11.9months.

Once a sufficient number of islet cells weretransplanted, all patients became independent ofexogenous insulin and had no further episodes of severehypoglycaemia.** Significant reductions from baseline inmean glycosylated haemoglobin levels were seen at 3and 6 months (from 8.4% at baseline to 5.7% at both 3and 6 months).

Patients also had significant reductions from baselinein mean 24-hour blood glucose levels and the meanamplitude of glycaemic excursions. Serum C-peptidelevels increased significantly from baseline.

The researchers suggest that the immunosuppressantregimen used, in addition to protecting againstautoimmune and alloimmune reactivity, ‘minimized thepossibility of damaging beta cells and increasing insulinresistance’.* Patients received oral sirolimus 0.2 mg/kg (loading dose) then 0.1mg/kg/day (adjusted to maintain concentrations of 12–15 ng/ml for thefirst 3 months and concentrations of 7–10 ng/ml thereafter), oraltacrolimus at an initial dosage of 1mg twice daily (subsequentlyadjusted to maintain a trough concentration of 3–6 ng/ml) and IVdaclizumab 1 mg/kg every 14 days for a total of 5 doses. Patientsundergoing a second transplantation procedure > 10 weeks after thefirst received an additional course of daclizumab.** Six patients required 2 transplantation procedures while theremaining patient required 3 procedures.

Shapiro AMJ, et al. Islet transplantation in seven patients with type 1 diabetesmellitus using a glucocorticoid-free immunosuppressive regimen. New EnglandJournal of Medicine 343: 230-238, 27 Jul 2000 800820658

» Editorial comment: The above-mentioned study has beenreleased by the NEJM via the Internet before its publication date,due to its potential therapeutic implications. A final version ofthe study report will be published in the 27 July 2000 issue ofthe NEJM.