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THE EFFECT OF INDOMETHACIN ON THE FEBRILE RESPONSE FOLLOWING OKT3 THERAPY1

Fifty renal transplant recipients with histologically documented acute allograft rejection were treated with OKT3 monoclonal antibody therapy. Group 1 (n=25) received standard premedication with steroids, acetaminophen, and diphenhydramine. Group 2 (n=25) received these agents plus indomethacin in an attempt to minimize the early adverse effects associated with OKT3. At 1 hr prior to the first dose of OKT3, 50 mg of indomethacin was administered orally followed by 25 mg every 6 hr for the next 48 hr. Demographics were similar in the two groups. Reversal of rejection occurred in 23 of 25 (92%) in group 1, and in 22 of 25 (88%) in group 2. Graft survival rates at six months after the rejection were 88% in group 1 and 80% in group 2. There was a single patient death in group 2, due to a suicide in a patient with a functioning kidney and pancreas graft. The maximum temperature was significantly diminished in the group receiving indomethacin during the first three days of OKT3 therapy. The percentage of patients with a maximum temperature <100°F was significantly higher in group 2: day 1—16% vs. 36%, day 2—12% vs. 48%, day 3—52% vs. 68% for group 1 and group 2, respectively. No serious side effects occurred in either group—however, subjective side effects were less common in group 2. Serum creatinine levels were similar in the two groups prior to rejection, at the start of OKT3 therapy, at the peak during OKT3 therapy, at the end of OKT3 therapy, and 30 days and 180 days post OKT3. The data indicate that the concurrent use of indomethacin with OKT3 appears to significantly decrease the initial febrile response without compromising renal function or the efficacy of OKT3 therapy.