Eculizumab for Prevention of Antibody-Mediated Rejection in Blood Group-Incompatible Renal Transplantation.

Antibody-mediated rejection (AMR) is one of the leading causes of allograft failure especially in patients undergoing ABO-incompatible (ABOi) renal transplantation. We hypothesized that complement inhibition with eculizumab, a C5 inhibitor, would protect against AMR and maintain graft function in ABOi renal transplant recipients. Four patients undergoing living donor kidney transplant from ABOi donors were treated with a 9-week eculizumab course without therapeutic plasma exchange, intravenous immunoglobulin, or splenectomy. All patients had successful transplants and have normal graft function at the time of last follow-up. There were no cases of AMR or acute cellular rejection. Of note, 2 patients were transplanted despite persistent ABO antibody titers of 1:32, conventionally considered a contraindication to proceed in standard protocols. Eculizumab is a promising option to prevent AMR with ABOi renal transplantation without the need for splenectomy, post-transplant therapeutic plasma exchange, and intravenous immunoglobulin. Future multicenter studies are needed to determine long-term efficacy and safety.

The first comparative double-blind trial on efficacy and safety of ergotamine based five-component combination and sumatriptan in migraine without aura.

BACKGROUND: Dihydroergotamine or ergotamine are the most effective preparations for aborting acute attacks of migraine without aura. OBJECTIVE: The aim of our study was to compare the efficacy and safety of ergotamine based five-component drug combination and sumatriptan in the treatment of moderate to severe acute attacks of migraine without aura. METHODS: The study was designed as a randomized, double-blind, double-dummy, placebo-controlled, parallel arm, multi-center clinical trial. The enrolled patients having migraine without aura were randomized to one of the study arms, ergotamine based five-component drug combination or sumatriptan. RESULTS: In total, 201 patients were randomized to one of the treatment arms. Higher percentage of patients was completely free of the headache two hours after dose administration in the ergotamine-based medication group compared to the sumatriptan group, regardless whether all (51.12 % vs 33.70 %) or only repeated attacks were taken into account (50.91 % vs 23.73 %); the salvage therapy (diclofenac) utilization rate was also lower in the ergotamine-based medication group (relative risk 0.61). Photophobia, phonophobia, and osmophobia were reversed more frequently in the ergotamine-based medication group (51.12 % vs 33.70 %), and failure to abort an attack of the migraine without aura occurred more frequently in the group treated with sumatriptan (1.1 % vs 4.9 %). The headache intensity two hours after ingestion of the study medication increased more frequently with sumatriptan, while other adverse events were rare in both groups. CONCLUSIONS: This study demonstrated higher efficacy and similar safety of ergotamine based fixed drug combination in comparison to sumatriptan, when used in the treatment of an acute attack of the migraine. HIPPOKRATIA 2018, 22(1): 17-22.

Rasburicase in cancer-related hyperuricemia.

Tumor lysis syndrome (TLS) is an oncological emergency consisting of several metabolic derangements: hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. The rupture of tumor cells in cancer patients can be spontaneous or caused by anticancer therapy. Clinical manifestations of TLS include nausea, anorexia, arrhythmias or renal failure. Prevention and treatment measures include aggressive hydration and concomitant antihyperuricemic therapy. Allopurinol has historically been the only available pharmacological option. Rasburicase was subsequently approved for the management of elevated plasma uric acid levels in adults. This recombinant urate oxidase converts uric acid to allantoin, a more soluble byproduct that is safely eliminated by the kidneys. Manufacturer-labeled dosing for rasburicase in the pediatric and adult populations is 0.2 mg/kg as a daily intravenous (i.v.) infusion for up to 5 days. This review summarizes several studies suggesting that flat, single rasburicase dosing regimens may be just as effective as weight-based dosing. The optimal, most cost-effective adult dose and schedule have yet to be determined.

Single-dose rasburicase for tumour lysis syndrome in adults: weight-based approach.

BACKGROUND: The optimal rasburicase dose for adult patients has not been determined. OBJECTIVE: To retrospectively examine use of rasburicase in our centre and to evaluate the effect of a single dose of rasburicase on urate and serum creatinine levels in our adult patients. METHOD: A retrospective chart review was conducted of all adult patients who received rasburicase for treatment of tumour lysis syndrome-associated hyperuricaemia at our academic, urban medical centre from July 2002 to October 2006. RESULT: Twenty-one patients received rasburicase with an average first dose of 0.15 +/- 0.03 mg/kg. The drug dosing was calculated based on the patients' ideal body weight (IBW) or adjusted body weight (aBW) for those who were more than 30% above their IBW. Patients experienced a mean serum urate reduction of 89.7 +/- 9.0% from the baseline through the first 24 h after a single rasburicase dose (11.4 +/- 4.5 mg/dL vs. 1.4 +/- 1.4 mg/dL, respectively, P < 0.001). The urate levels remained within normal limits (<8 mg/dL) in all the patients for 48 h after a single dose of rasburicase. The major limitation of our study is that in 18 of 21 patients we lacked adequate documentation to ascertain that the blood samples sent for urate analysis after drug administration were handled according to the manufacturer's recommendations. However, in this small group of patients, we observed that the effect of rasburicase on serum urate was similar to the total study population. The effect was sustained for 48 h after a single dose. Serum creatinine levels at 24-72 h after the single rasburicase dose were not significantly different from baseline (1.8 mg/dL vs. 2.3 mg/dL, respectively, P = 0.14). CONCLUSION: Rasburicase is an effective treatment for patients with hyperuricaemia and may aid in the prevention of hyperuricaemia-associated nephrotoxicity. From our experience, a single dose of 0.15 mg/kg (IBW or aBW) of rasburicase appears to effectively decrease and maintain urate levels within normal limits for 48 h.