1 Centre for Transplant and Renal Research, Westmead Institute for Medical Research, University of Sydney at Westmead Hospital, Sydney, NSW, Australia. 2 Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium. 3 Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL. 4 Division of Organ Transplantation, Feinberg School of Medicine, Northwestern University, Chicago, IL. 5 Department of Renal Medicine, University of Sydney at Royal Prince Alfred Hospital, Australia. 6 The Division of Nephrology, St. Paul's Hospital, Vancouver, British Columbia, Canada. 7 Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. 8 Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. 9 Transplant Immunology Laboratory, University of Manitoba, Winnipeg Blood Centre, Winnipeg, Manitoba, Canada. 10 Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, OH. 11 Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH. 12 Department of Surgery, University of California San Francisco, San Francisco, CA. 13 Department of Nephrology, Hospital Universitari Vall d'Hebron, Universitat Autónoma Barcelona, Barcelona, Spain. 14 Department of Medicine, University of Cincinnati, College of Medicine, Cincinnati, OH. 15 Division of Transplantation, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD. 16 Department of Nephrology, Universitätsklinikum Charité, Humboldt University, Berlin, Germany. 17 The Comprehensive Transplant Center, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA. 18 Service de Néphrologie-Transplantation, Hôpital Necker, Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Paris France. 19 INSERM U845, Hôpital Necker, Paris, France. 20 Department of Nephrology and Kidney Transplantation, Saint-Louis Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. 21 Division of Transplant Surgery, University of California San Francisco, San Francisco, CA. 22 Division of Transplantation, Department of Surgery, The Johns Hopkins University, Baltimore, MD. 23 Departments of Surgery and Immunology, von Liebig Transplant Center, Mayo Clinic, Rochester, MN. 24 Transplant Surgery Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 25Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH. 26 Stanford University School of Medicine, Stanford, CA.
Transplantation. 2017 Jul;101(7):1527-1534. doi: 10.1097/TP.0000000000001648.
Currently trials of immunosuppression in transplantation are in decline because their objectives remain focused on improving acute rejection rates and graft survival in the first 12 months. With 1 year renal graft survival rates of greater than 90% the best that can be hoped for is noninferiority trial outcomes compared with current standard of care. Current trial design is not leading to novel therapies improving long-term outcomes and safety, and hence important unmet clinical needs in transplantation remain unanswered. Issues that need to be addressed include but are not limited to: prevention of subclinical rejection in the first year, better 5- and 10-year graft outcomes, more effective treatment for high immunological risk and sensitized (including donor-specific antibody) patients, immunosuppressive combinations that are better tolerated by patients with fewer side effects and less morbidity and mortality. In September 2015, the Transplantation Society convened a group of transplant clinical trial experts to address these problems. The aims were to substantially realign the priorities of clinical trials for renal transplant immunosuppression with the current unmet needs and to propose new designs for clinical trials for transplant immunosuppression. Moving forward, the transplant community needs to provide trial data that will identify superior treatment options for patient subgroups and allow new agents to be evaluated for efficacy and safety and achieve timely regulatory approval. Trial designs for new transplant immunosuppression must be intelligently restructured to ensure that short- and long-term clinical outcomes continue to improve.
目前，移植领域的免疫抑制试验正在减少，因为其目标仍然集中在提高前 12 个月的急性排斥率和移植物存活率。目前，肾移植 1 年存活率超过 90%，最好的结果是与当前的标准治疗相比，非劣效性试验结果。目前的试验设计并没有导致新的疗法改善长期结果和安全性，因此移植领域的一些重要未满足的临床需求仍未得到解决。需要解决的问题包括但不限于：预防第一年的亚临床排斥反应、改善 5 年和 10 年的移植物结果、为高免疫风险和致敏（包括供体特异性抗体）患者提供更有效的治疗、免疫抑制组合在患者中具有更好的耐受性，副作用和发病率及死亡率更低。2015 年 9 月，移植学会召集了一组移植临床试验专家来解决这些问题。其目的是大幅调整肾移植免疫抑制临床试验的优先事项，以满足当前的未满足需求，并为移植免疫抑制的临床试验提出新的设计。展望未来，移植界需要提供试验数据，以确定患者亚组的更佳治疗选择，并允许新药物进行疗效和安全性评估，并及时获得监管部门的批准。新的移植免疫抑制试验设计必须进行智能重构，以确保短期和长期的临床结果继续得到改善。
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