Budde K, Glander P, Diekmann F, Dragun D, Waiser J, Fritsche L, Neumayer H-H
University Hospital Charité, Berlin, Germany.
Transplant Proc. 2004 Mar;36(2 Suppl):524S-527S. doi: 10.1016/j.transproceed.2003.12.042.
Mycophenolate mofetil (MMF), in combination with cyclosporine and corticosteroids, improves long-term graft function and survival in renal transplant recipients. However, optimal MMF therapy may be limited by gastrointestinal (GI) intolerance, which may result in the need for MMF dose reduction, interruption, or discontinuation, leading to increased risk of acute rejection. Enteric-coated mycophenolate sodium (EC-MPS) is an advanced formulation delivering mycophenolic acid (MPA), developed with the objective of improving MPA-related upper GI adverse events. A pivotal, 12-month, phase III, randomized, multicenter, double-blind, double-dummy, parallel group study investigated whether stable renal transplant patients can be converted from MMF to EC-MPS therapy without compromising tolerability or efficacy. Stable renal transplant recipients received either MMF, 1000 mg b.i.d. (n=159), or EC-MPS, 720 mg b.i.d. (n=163), for 12 months. The incidence of GI adverse events was comparable between both treatment groups at 3 and 6 months, but there was a trend toward reduced severity of GI side effects in the EC-MPS group. There were fewer serious adverse events with EC-MPS and significantly fewer serious infections (P<.05). This comparable safety profile for EC-MPS and MMF also extended to elderly patients and patients with diabetes at baseline. For the composite efficacy variable of biopsy-proven acute rejection, graft loss, death, or loss to follow-up, EC-MPS had a lower 12-month efficacy failure rate (EC-MPS: 7.5% vs MMF: 12.3%; P=ns). These data demonstrate that stable renal transplant recipients receiving MMF can be converted to EC-MPS with no efficacy or tolerability compromise.
霉酚酸酯(MMF)与环孢素和皮质类固醇联合使用,可改善肾移植受者的长期移植肾功能和生存率。然而,最佳的MMF治疗可能会受到胃肠道(GI)不耐受的限制,这可能导致需要减少MMF剂量、中断或停药,从而增加急性排斥反应的风险。肠溶包衣的霉酚酸钠(EC-MPS)是一种递送霉酚酸(MPA)的先进制剂,其研发目的是改善与MPA相关的上消化道不良事件。一项关键的、为期12个月的III期随机、多中心、双盲、双模拟、平行组研究,调查了稳定的肾移植患者能否从MMF转换为EC-MPS治疗而不影响耐受性或疗效。稳定的肾移植受者接受MMF,每日两次,每次1000mg(n = 159),或EC-MPS,每日两次,每次720mg(n = 163),持续12个月。在3个月和6个月时,两个治疗组的胃肠道不良事件发生率相当,但EC-MPS组胃肠道副作用的严重程度有降低的趋势。EC-MPS的严重不良事件较少,严重感染明显较少(P<0.05)。EC-MPS和MMF这种相当的安全性也适用于基线时的老年患者和糖尿病患者。对于活检证实的急性排斥反应、移植失败、死亡或失访的综合疗效变量,EC-MPS的12个月疗效失败率较低(EC-MPS:7.5% vs MMF:12.3%;P=无统计学意义)。这些数据表明,接受MMF的稳定肾移植受者可以转换为EC-MPS,而不会影响疗效或耐受性。