eculizumab (Ablyze)

Long-Term Therapy with Eculizumab Biosimilar in Patients with Atypical Haemolytic Uraemic Syndrome: Outcomes of a Prospective Observational Study.

Kotenko Oleg O, Kozlovskaya Natalia N, Emirova Khadizha K, Muzurov Alexander A et al.

The objective of a multicentre, prospective, observational study of an eculizumab biosimilar (Elizaria®) was to analyse the efficacy and safety of long-term complement inhibitor therapy in patients with atypical haemolytic uraemic syndrome (aHUS). The study included 50 patients aged 1 to 55 years, with 42% of them under the age of 18. The patients received the eculizumab biosimilar in routine clinical practice within 56 weeks; 19 patients (38%) had been treated with eculizumab prior to enrolment, whereas 31 patients (62%) were naive to complement inhibitors. By the end of the study, an increase in platelet count of 39.48±21.7×109/L and 33.61±24.06×109/L was reported in treatment-naive and treatment-experienced patients, respectively. By the end of the study, 96% of treatment-experienced patients and 100% of treatment-naive patients had normal platelet counts. The mean LDH activity did not change significantly, with levels of 253.84±122.22 U/L registered at screening and 245.24±93.52 U/L at the end of the study. In total, 39 patients (77.6%) at Week 21 and 40 patients (80%) at Week 52 had no thrombotic microangiopathy (TMA) events. During the study, the proportion of patients with a complete TMA response increased significantly, rising to 8% (P = 0.046). The proportion of patients with an eGFR improvement of 15 mL/min/1.73 m2 and more at Week 52 was 12%. During the safety assessment, 63 adverse events not related to the investigational medicinal product were reported. Long-term complement inhibitor therapy with the eculizumab biosimilar in patients with aHUS has demonstrated a stable effect, a favourable safety profile and low immunogenicity.

Hockman A, Anuskiewicz S, Brennan E, et al. Efficacy of eculizumab discontinuation in atypical hemolytic uremic syndrome: a systematic review and meta-analysis. Blood Adv. 2025;9(23):6096-6107.

Gemcitabine-sirolimus synergy associated thrombotic microangiopathy in a renal transplant recipient with mesenteric leiomyosarcoma: A case report.

Motla Vishaal V, Baig Usman U, Mulloy Laura L, Nakkar Talal T et al.

Mesenteric leiomyosarcoma, a rare tumor originating from the smooth muscle of the mesentery, that may require treatment with gemcitabine based chemotherapy in advanced stages. Gemcitabine usage has been associated with the development of thrombotic microangiopathy, a risk which can be increased by concurrent use of sirolimus. We present the case of a young Caucasian woman with a renal transplant who developed an aggressive leiomyosarcoma. While on gemcitabine, she was noted to have acute kidney injury. Biopsy of the renal allograft revealed histological findings consistent with thrombotic microangiopathy. Sirolimus was replaced with tacrolimus, and gemcitabine was discontinued. Despite treatment with eculizumab, the allograft function continued to decline, leading to graft failure, and the patient had to be started on renal replacement therapy. This case highlights the possible synergy of gemcitabine and sirolimus in the pathogenesis of de novo thrombotic microangiopathy.

Biologics in Kidney Transplantation: Why and How Should We Personalize Their Dosage?

Arrivé Capucine C, Hotot Marie M, Jourdil Jean-François JF, Stanke-Labesque Françoise F

The therapeutic arsenal of immunosuppressive drugs in kidney transplantation has recently expanded with the introduction of biologics, approved or used off-label, that specifically target the immune system. Although therapeutic drug monitoring is well established for calcineurin inhibitors, its utility for biological immunosuppressants remains unclear. The objective of this narrative review was to evaluate whether biologics used to prevent or treat renal allograft rejection could be suitable candidates for therapeutic drug monitoring. This review provides (1) a comprehensive and up-to-date synthesis on the pharmacological targets of biologics used in kidney transplantation, (2) assesses the interindividual variability of the pharmacokinetics and pharmacokinetic/pharmacodynamic relationships of key biologics, including belatacept, tocilizumab, rituximab, basiliximab, alemtuzumab, eculizumab, ravulizumab, daratumumab, and imlifidase and (3) describes the analytical methods available for their quantification. This review underscores that, although none of these biologics currently meet all criteria for routine therapeutic drug monitoring, emerging clinical evidence indicates that individualized dosing could enhance both therapeutic outcomes and cost effectiveness. It also discusses future directions for improving pharmacokinetic/pharmacodynamic knowledge on biological therapies in kidney transplant recipients and places in perspective the potential of therapeutic drug monitoring to improve the benefit-risk ratio and cost effectiveness of these biologics.