BOSTON—Alemtuzumab use is associated with a lower incidence of acute rejection and infection compared to rabbit anti-thymocyte globulin (rATG) induction in kidney and pancreas transplant recipients, regardless of age or ethnicity, according to a new study presented at the Infectious Diseases Society of America annual meeting.

“What we found somewhat surprising was that there was a lower incidence of biopsy-proven acute rejection in patients receiving alemtuzumab induction,” said study investigator Robert Stratta, MD, Director of Transplantation at Wake Forest University in Winston-Salem, N.C.  “We found this was consistent in a number of patient subpopulations. We looked at low and high immunologic responders and we looked at African-Americans versus the Caucasians.”

An increased risk of infectious complications (ICs) after kidney/pancreas transplantation is an ongoing major concern when using lymphocyte depleting antibody induction agents such as alemtuzumab (Alem) and rATG, according to the investigators.  

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In a randomized trial that enrolled 222 adult kidney/pancreas transplant patients, 113 subjects received single-dose Alem (30 mg) and 109 received alternate day rATG (1.5 mg/kg) induction. All patients received maintenance therapy consisting of tacrolimus, mycophenolic acid, and risk stratification to determine early steroid elimination. The two treatment arms were similar with respect to demographic characteristics.

Patients received prophylaxis for fungal infections at four and eight weeks, pneumocystis prophylaxis at 12 months, and prophylaxis against primary cytomegalovirus at three and six months. ICs were graded according to National Institute of Health [NIH] Clinical Toxicity Criteria.

ICs were graded according to NIH Clinical Toxicity Criteria (CTCAE version 3.0).

After a median follow-up of 24 months, the overall patient survival rate was 95%, the kidney survival rate was 90%, and the pancreas survival rate was 85%. The researchers observed no significant difference between study arms.

“We also found that the single most important risk factor for infection was the presence of biopsy proven acute rejection,” Dr. Stratta told Renal & Urology News.

The incidence of biopsy proven acute rejection (BPAR) was lower in the Alem recipients (16%) than in the rATG group (26%). The presence of BPAR increased the overall risk of ICs from 41% to 72%.   ICs developed in 61 Alem patients (54%) and 81 rATG patients (74%).

The investigators found no significant differences in the incidence or severity of ICs according to recipient ethnicity either in the Alem or rATG induction groups. However, the incidence of viral and fungal infections was higher in Caucasians compared with African Americans receiving Alem, but not rATG.

“There are previous data in the literature suggesting that there may be differential risk of infection in transplant recipients according to ethnicity and particularly with increasing recipient age,” Dr. Stratta said. “We used a standard scoring system for grading infections and looked at the incidence of infections in the blacks versus whites and we really didn’t find any significant differences.”

Among patients older than 60 years, the researchers observed no differences in the number of patients with infection or in the rate of hospitalization for infection compared with younger patients. The severity of ICs in older patients compared with younger patients was similar regardless of recipient ethnicity.

It had been theorized that older adults, because of their aging immune systems, would be less likely to reject their transplanted organ and so would require less immunosuppression, Dr. Stratta said. “But because more older adult patients are getting expanded criteria donor kidneys their risk of rejection is higher with those types of kidneys. So if you under immunosuppress patients you won’t have as good an outcome,” he explained.