Lipkovich Ilya, Jacobson Jennie G, Hardy Thomas A, Hoffmann Vicki Poole
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
BMC Psychiatry. 2008 Sep 15;8:78. doi: 10.1186/1471-244X-8-78.
To make well informed treatment decisions for their patients, clinicians need credible information about potential risk for substantial weight gain. We therefore conducted a post-hoc analysis of clinical trial data, examining early weight gain as a predictor of later substantial weight gain.
Data from 669 (Study 1) and 102 (Study 2) olanzapine-treated patients diagnosed with schizophrenia, schizophreniform, or schizoaffective disorder were analyzed to identify and validate weight gain cut-offs at Weeks 1-4 that were predictive of substantial weight gain (defined as an increase of > or = 5, 7, 10 kg or 7% of baseline weight) after approximately 30 weeks of treatment. Baseline characteristics alone, baseline characteristics plus weight change from baseline to Weeks 1, 2, 3 or 4, and weight change from baseline to Weeks 1, 2, 3, or 4 alone were evaluated as predictors of substantial weight gain. Similar analyses were performed to determine BMI increase cut-offs at Weeks 1-4 of treatment that were predictive of substantial increase in BMI (1, 2 or 3 kg/m2 increase from baseline).
At Weeks 1 and 2, predictions based on early weight gain plus baseline characteristics were more robust than those based on early weight gain alone. However, by Weeks 3 and 4, there was little difference between the operating characteristics associated with these two sets of predictors. The positive predictive values ranged from 30.1% to 73.5%, while the negative predictive values ranged from 58.1% to 89.0%. Predictions based on early BMI increase plus baseline characteristics were not uniformly more robust at any time compared to those based on early BMI increase alone. The positive predictive values ranged from 38.3% to 83.5%, while negative predictive values ranged from 42.1% to 84.7%. For analyses of both early weight gain and early BMI increase, results for the validation dataset were similar to those observed in the primary dataset.
Results from these analyses can be used by clinicians to evaluate risk of substantial weight gain or BMI increase for individual patients. For instance, negative predictive values based on data from these studies suggest approximately 88% of patients who gain less than 2 kg by Week 3 will gain less than 10 kg after 26-34 weeks of olanzapine treatment. Analysis of changes in BMI suggests that approximately 84% of patients who gain less than .64 kg/m2 in BMI by Week 3 will gain less than 3 kg/m2 in BMI after 26-34 weeks of olanzapine treatment. Further research in larger patient populations for longer periods is necessary to confirm these results.
为了为患者做出明智的治疗决策，临床医生需要有关显著体重增加潜在风险的可靠信息。因此，我们对临床试验数据进行了一项事后分析，将早期体重增加作为后期显著体重增加的预测指标。
分析了669名（研究1）和102名（研究2）接受奥氮平治疗的精神分裂症、分裂样精神病或分裂情感性障碍患者的数据，以确定并验证在第1至4周时可预测约30周治疗后显著体重增加（定义为体重增加≥5、7、10千克或基线体重的7%）的体重增加临界值。单独的基线特征、基线特征加上从基线到第1、2、3或4周的体重变化，以及仅从基线到第1、2、3或4周的体重变化被评估为显著体重增加的预测指标。进行了类似分析，以确定治疗第1至4周时可预测BMI显著增加（较基线增加1、2或3千克/平方米）的BMI增加临界值。
在第1周和第2周，基于早期体重增加加上基线特征的预测比仅基于早期体重增加的预测更可靠。然而，到第3周和第4周时，这两组预测指标的操作特征之间几乎没有差异。阳性预测值范围为30.1%至73.5%，而阴性预测值范围为58.1%至89.0%。与仅基于早期BMI增加的预测相比，基于早期BMI增加加上基线特征的预测在任何时候都并非始终更可靠。阳性预测值范围为38.3%至83.5%，而阴性预测值范围为42.1%至84.7%。对于早期体重增加和早期BMI增加的分析，验证数据集的结果与在主要数据集中观察到的结果相似。
临床医生可利用这些分析结果评估个体患者显著体重增加或BMI增加的风险。例如，基于这些研究数据的阴性预测值表明，在第3周体重增加少于2千克的患者中，约88%在接受奥氮平治疗26 - 34周后体重增加少于10千克。BMI变化分析表明，在第3周BMI增加少于0.64千克/平方米的患者中，约84%在接受奥氮平治疗26 - 34周后BMI增加少于3千克/平方米。需要在更大的患者群体中进行更长时间的进一步研究以证实这些结果。
