Reduce Steroids to Tame Diabetes Post Transplant : Two studies show benefits with alemtuzumab induction therapy.


CHICAGO — Steroid minimization in patients undergoing heart transplantation may be associated with improved survival among patients with existing diabetes as well as a lower incidence of posttransplant, new-onset diabetes, according to research findings reported at the meeting.

In one retrospective study, survival was significantly lower in diabetic vs. nondiabetic transplant patients (about 65% vs. about 80%, respectively) when steroid immunosuppression was not minimized, but survival was similar (about 80% for diabetic vs. 85% for nondiabetic patients) in patients who did have steroid minimization, Dr. Jeffrey J. Teuteberg reported.

The first group included 200 patients who had transplants between 1998 and 2003 and received tacrolimus, mycophenolate, and gradual prednisone taper for immunosuppression. The second group consisted of 217 patients who underwent transplants between 2004 and 2008 and received tacrolimus, mycophenolate, and steroid minimization via rapid taper or alemtuzumab induction therapy, said Dr. Teuteberg of the Cardiovascular Institute at the University of Pittsburgh.

Steroid-free status at 3 years also was improved by steroid minimization. For example, almost all group 2 patients were steroid free at 3 years, compared with 75% of group 1 patients. Rejection rates were similar in both groups.

Differences between patient groups included older age, racial differences, less sensitization, and less ventricular assist device usage among the diabetic patients in group 2 vs. group 1.

“Clearly, there are multiple factors [influencing] why our patients with diabetes are doing better now” he said. A multivariate model is being developed to evaluate how strong a predictor diabetes is by era, and the investigators plan to examine more closely how comorbidities such as renal insufficiency and peripheral vascular disease affect outcomes.

In another study from the University of Pittsburgh, the use of alemtuzumab induction followed by steroid-free maintenance immunosuppression in nondiabetic patients was associated with a lower incidence of new diabetes in the first 3 years after transplant, Raquel Jones reported.

That study included 110 heart transplant recipients who received alemtuzumab induction and 110 historical controls who received no induction therapy. The treatment and control groups had similar baseline characteristics, including body mass index, noted Ms. Jones, a medical student at the University of Pittsburgh.

Donor characteristics also were similar, except the treatment-group donors were significantly older (36 vs. 32 years) with longer ischemic times (209 vs. 171 minutes).

The treatment-group patients received alemtuzumab induction after October 2006, when the center began using such induction routinely. There were 110 control patients treated during October 2001–October 2006 without induction. Both groups received tacrolimus and mycophenolate for chronic immunosuppression, but the treatment group received dose-reduced tacrolimus and no steroids.

Steroid use in the control group at 6 months, 12 months, 2 years, and 3 years was 93%, 56%, 18%, and 0%, respectively, vs. 0% at all time points in the alemtuzumab induction group, Ms. Jones noted.

The baseline incidence of diabetes—defined as the use of any diabetic treatment—was 32% and 29% in the treatment and control groups, respectively. Fewer cases of new diabetes post transplant, relative to baseline, occurred in treatment group vs. the controls (8% vs. 44% of cases at 6 months; 8% vs. 29% of cases at 12 months; 7% vs. 22% of cases at 2 years; and 8% vs. 21% of cases at 3 years). New-onset cases in the noninduction group trended downward in tandem with steroid weaning.

No differences were seen between the two groups with regard to control and management of diabetes, including insulin use, at 3-year follow-up, Ms. Jones said.

Other data from this cohort reported at the meeting showed that alemtuzumab induction and steroid-free immunosuppression are associated with good survival and good rejection-free survival. Together, the findings contribute to the expanding evidence of the value of alemtuzumab induction with steroid-free maintenance in heart transplant patients. Previous studies have demonstrated its merit in other types of transplant, including renal and lung transplant.

Dr. Teuteberg and Ms. Jones discussed off-label use of alemtuzumab, but had no other relevant disclosures.

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