Fujioka K, Plodkowski R, O'Neil P M, Gilder K, Walsh B, Greenway F L
Scripps Clinic, La Jolla, CA, USA.
Weight Management Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA.
Int J Obes (Lond). 2016 Sep;40(9):1369-75. doi: 10.1038/ijo.2016.67. Epub 2016 Jun 22.
BACKGROUND/OBJECTIVES: Weight management medications increase the likelihood that patients will achieve clinically meaningful improvements in cardiovascular, metabolic and other weight-related measures of health. However, the weight loss achieved with any weight management intervention can vary widely among individuals, and patients who do not respond to pharmacotherapy by achieving clinically meaningful weight loss should discontinue therapy. We characterized 1-year weight loss in the phase 3 clinical trial program of the weight management medication, naltrexone/bupropion 32/360 mg (NB), as well as the relationship between early weight loss and long-term weight loss, particularly with respect to participants who achieved the clinically recommended threshold of ⩾5% weight loss by Week 16.
PARTICIPANTS/METHODS: Data from participants from each of the four phase 3, randomized, placebo-controlled, 56-week clinical trials with NB were pooled (modified intent-to-treat population; NB N=2043, Placebo N=1319). This exploratory analysis examined the relationship between participant achievement of various weight loss thresholds early in treatment (at Week 8, 12 or 16) and the associated weight loss at Week 56 (Completers population; NB N=1310, Placebo N=763).
In the NB participants who completed 1 year of treatment, weight loss of at least 5% at Week 16 (n=873) was associated with least-squares mean weight loss of 11.7% at Week 56 and 85% of these participants had Week 56 weight loss of ⩾5%. Eighty percent (95% confidence interval: 78-82%) of the participants who would, and would not, achieve ⩾5% weight loss at Week 56 were correctly identified using the clinically recommended threshold of ⩾5% at Week 16. Safety and tolerability of NB was similar to previously published reports.
Participants who meet the Week 16 threshold of ⩾5% weight loss are likely to maintain clinically significant weight loss after 1 year of treatment. Further evaluations are required to evaluate improvements in measures of cardiovascular and metabolic risk.
背景/目的：体重管理药物增加了患者在心血管、代谢及其他与体重相关的健康指标方面取得具有临床意义改善的可能性。然而，任何体重管理干预措施所实现的体重减轻在个体间差异可能很大，对药物治疗无反应、未实现具有临床意义体重减轻的患者应停止治疗。我们在体重管理药物纳曲酮/安非他酮32/360毫克（NB）的3期临床试验项目中，对1年的体重减轻情况进行了特征分析，以及早期体重减轻与长期体重减轻之间的关系，特别是对于在第16周达到临床推荐的≥5%体重减轻阈值的参与者。
参与者/方法：汇总了四项使用NB的3期、随机、安慰剂对照、56周临床试验中各参与者的数据（改良意向性治疗人群；NB组N = 2043，安慰剂组N = 1319）。这项探索性分析研究了治疗早期（第8周、12周或16周）参与者达到不同体重减轻阈值与第56周相关体重减轻之间的关系（完成者人群；NB组N = 1310，安慰剂组N = 763）。
在完成1年治疗的NB参与者中，第16周体重减轻至少5%（n = 873）与第56周最小二乘平均体重减轻11.7%相关，且这些参与者中有85%在第56周体重减轻≥5%。使用第16周临床推荐的≥5%阈值，能够正确识别出80%（95%置信区间：78 - 82%）在第56周会或不会实现≥5%体重减轻的参与者。NB的安全性和耐受性与先前发表的报告相似。
在第16周达到≥5%体重减轻阈值的参与者在治疗1年后可能维持具有临床意义显著的体重减轻。需要进一步评估心血管和代谢风险指标的改善情况。
