University Hospital Carl Gustav Carus at the Technische Universität Dresden, Department of Internal Medicine III, Division of Nephrology, Dresden, Germany.
Albert-Ludwigs University Freiburg, Department of General Surgery, Freiburg, Germany.
Nephrol Dial Transplant. 2023 Dec 20;39(1):141-150. doi: 10.1093/ndt/gfad130.
We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled 1-year "Harmony" trial with 587 predominantly deceased-donor kidney transplant recipients randomized either to basiliximab or rabbit antithymocyte globulin induction therapy and compared with standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil and corticosteroids.
The 5-year post-trial follow-up (FU) data were obtained in an observational manner at a 3- and a 5-year visit only for those Harmony patients who consented to participate and covered clinical events that occurred from the second year onwards.
Biopsy-proven acute rejection and death-censored graft loss rates remained low and independent of RSWD. Rapid steroid withdrawal was an independent positive factor for patient survival (adjusted hazard ratio 0.554, 95% confidence interval 0.314-0.976; P = .041).The reduced incidence of post-transplantation diabetes mellitus in RSWD patients during the original 1-year study period was not compensated by later incidences during FU. Incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor-specific antibody formation or kidney function did not differ during FU period.
With all the limitations of a post-trial FU study, the Harmony FU data confirm excellent efficacy and beneficial safety aspects of RSWD under modern immunosuppressive therapy over the course of 5 years after kidney transplantation in an immunologically low-risk, elderly population of Caucasian kidney transplant recipients. Trial registration: Clinical trial registration number: Investigator Initiated Trial (NCT00724022, FU study DRKS00005786).
我们之前报道了在一项随机对照的为期 1 年的“和谐”试验中，快速类固醇撤药（RSWD）的优异疗效和安全性改善，该试验纳入了 587 名主要来自已故供体的肾移植受者，他们被随机分为巴利昔单抗或兔抗胸腺细胞球蛋白诱导治疗组，并与包括巴利昔单抗、低剂量每日他克莫司、霉酚酸酯和皮质类固醇的标准免疫抑制治疗进行比较。
仅对同意参加并涵盖从第二年开始发生的临床事件的 Harmony 患者，以观察方式获得了 5 年的试验后随访（FU）数据，随访时间为 3 年和 5 年。
活检证实的急性排斥反应和死亡相关移植物丢失率仍然较低，且独立于 RSWD。快速类固醇撤药是患者生存的独立积极因素（调整后的危险比 0.554，95%置信区间 0.314-0.976；P=0.041）。在原始的 1 年研究期间，RSWD 患者的移植后糖尿病发病率降低，但在 FU 期间并未得到补偿。在 FU 期间，其他重要结局参数（如机会性感染、恶性肿瘤、心血管发病率/危险因素、供体特异性抗体形成或肾功能）的发病率无差异。
尽管存在试验后 FU 研究的所有局限性，但“和谐”FU 数据证实，在免疫低风险、老年白种人肾移植受者中，在现代免疫抑制治疗下，RSWD 在肾移植后 5 年内具有优异的疗效和有益的安全性。
临床试验注册号：研究者发起的试验（NCT00724022，FU 研究 DRKS00005786）。
