Eight-Year Results of the Spiesser Study, a Randomized Trial Comparing de Novo Sirolimus and Cyclosporine in Renal Transplantation

Philippe Gatault (1) , Dominique Bertrand , Matthias Buchler (2) , Charlotte Colosio (3) , Bruno Hurault De Ligny , Pierre-François Weestel (4, 5) , Jean-Philippe Rerolle (6) , Antoine Thierry (7, 8) , Johnny Sayegh (9) , Bruno Moulin , Renaud Snanoudj (10) , Joseph Rivalan (11) , Anne-Elisabeth Heng (12) , Benedicte Sautenet (2, 13, 14) , Yvon Lebranchu (1)

1 Service de néphrologie et immunologie clinique [CHRU Tours]
2 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
3 Hôpital universitaire Robert Debré [Reims]
4 Affectations Mineralisantes du Systeme Cardiovasculaire : Calcifications Arterielles et Valvulaires Aortiques
5 Service de dyalise et transplantation
6 Service de Néphrologie, Dialyse, Transplantations [CHU Limoges]
7 IRTOMIT [Poitiers] - Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques [U 1082]
8 Service de néphrologie - hémodialyse et transplantation rénale
9 Department of Kidney Transplantation CHU Angers
10 Service de néphrologie adultes [CHU Necker]
11 Service de néphrologie [Rennes]
12 CHU Estaing [Clermont-Ferrand]
13 Université Francois Rabelais [Tours]
14 SPHERE - MethodS in Patients-centered outcomes and HEalth ResEarch

We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death-censored graft survival (log-rank compared), de novo DSA appearance, risk of malignancy, post-transplant diabetes mellitus (PTDM), and anemia. Intent-to-treat and on-treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death-censored graft survival (P = 0.858). In conditional intent-to-treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 ± 27.3 ml/min vs. 47.8 ± 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long-term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus.

Mots clés: Adult; Analysis of Variance; Cause of Death; clinical trial; Cyclosporine; Dose-Response Relationship; Drug; Drug Administration Schedule; Female; Follow-Up Studies; Graft Rejection; Graft Survival; human leukocyte antigen-antibody posttransplantation; Humans; immunosuppression; Immunosuppression; Immunosuppressive Agents; Kaplan-Meier Estimate; kidney transplantation; Kidney Transplantation; Male; Middle Aged; Prospective Studies; Risk Assessment; Sirolimus; Statistics; Nonparametric; Survival Rate; target of rapamycin-inhibitors; Time Factors; Treatment Outcome

Domaines: Sciences du Vivant [q-bio]

Philippe Gatault, Dominique Bertrand, Matthias Buchler, Charlotte Colosio, Bruno Hurault De Ligny, et al.. Eight-Year Results of the Spiesser Study, a Randomized Trial Comparing de Novo Sirolimus and Cyclosporine in Renal Transplantation. Transplant International, 2016, 29 (1), pp.41-50. ⟨10.1111/tri.12656⟩. ⟨hal-03157732⟩