Background: Thiazolidinedione (TZD) exerts anti-proliferative effects on multiple myeloma (MM) cells. However, there has not been any human study investigating the risk of MM associated with TZD use. Methods: We used Taiwan’s National Health Insurance database to identify 423,949 patients who had been newly diagnosed with diabetes mellitus between 1999 and 2005. After excluding ineligible patients, 86,999 pairs of patients with and without the use of TZD (rosiglitazone or pioglitazone) that had been matched based on propensity score were selected for a follow-up for MM until 31 December 2011. The hazard ratios for MM were estimated using Cox regression and weighted using a propensity score. Results: After a median follow-up of 4.6 years and 4.7 years in ever users and never users of TZD, 32 and 47 cases were diagnosed with MM, respectively. A 35% lower risk (though not statistically significant) was observed among ever users (hazard ratio 0.652, 95% confidence interval: 0.416–1.023,p= 0.0625). When ever users were divided by the median (15 months) cumulative duration of TZD therapy, the hazard ratios (95% confidence interval) for the lower and upper medians were 0.706 (0.394–1.264) and 0.603 (0.346–1.051), respectively. When treated as a continuous variable, the hazard ratio for every 1-month increment of the cumulative duration was 0.980 (95% confidence interval: 0.963–0.997,p= 0.0185). In the age subgroup analysis, a significantly lower risk could be seen in the older age subgroup of ≥65 years (hazard ratio 0.550, 95% confidence interval: 0.305–0.992,p= 0.0468). Additional analyses suggested that there were no interactions between TZD and some medications and between TZD and some clinical diagnoses, and that the use of TZD as a preventive drug for MM might not be cost-effective because a number-needed-to-treat of 5800 was too large. Survival analyses suggested that ever users had a significantly lower risk of death when all patients were analyzed (hazard ratio: 0.84, 95% confidence interval: 0.81–0.87,p< 0.0001 via a log-rank test) or when patients who developed MM were analyzed (hazard ratio: 0.40, 95% confidence interval: 0.19–0.86,p= 0.0153 via a log-rank test). Conclusions: In Taiwanese patients with type 2 diabetes mellitus, TZD use is associated with a borderline lower risk of MM, which is more remarkable in patients aged ≥65 years. Because of the low incidence of MM, the use of TZD for the prevention of MM may not be cost-effective. Patients who have been treated with TZD may have a survival advantage. Future research is required to confirm the findings.
背景：噻唑烷二酮类药物对多发性骨髓瘤细胞具有抗增殖作用，但尚无人类研究探讨使用TZD与MM风险的相关性。方法：利用台湾全民健康保险数据库，识别1999年至2005年间新诊断为糖尿病的423,949例患者。排除不符合条件的患者后，根据倾向评分匹配出86,999对使用与未使用TZD（罗格列酮或吡格列酮）的患者，随访至2011年12月31日以观察MM发生情况。采用Cox回归模型估计MM风险比，并基于倾向评分进行加权分析。结果：在TZD使用者和非使用者的中位随访时间分别为4.6年和4.7年后，分别诊断出32例和47例MM病例。TZD使用者风险降低35%（风险比0.652，95%置信区间：0.416–1.023，p=0.0625），但未达到统计学显著性。按TZD累积治疗时间中位数（15个月）分层分析，低于和高于中位数组的风险比（95%置信区间）分别为0.706（0.394–1.264）和0.603（0.346–1.051）。将累积治疗时间作为连续变量分析，每增加1个月的风险比为0.980（95%置信区间：0.963–0.997，p=0.0185）。年龄亚组分析显示，≥65岁老年亚组风险显著降低（风险比0.550，95%置信区间：0.305–0.992，p=0.0468）。进一步分析表明，TZD与某些药物及临床诊断之间不存在交互作用，且因需治疗人数高达5800例，使用TZD预防MM可能不具备成本效益。生存分析显示：在所有患者中，TZD使用者死亡风险显著降低（风险比：0.84，95%置信区间：0.81–0.87，对数秩检验p<0.0001）；在发生MM的患者中，TZD使用者死亡风险亦显著降低（风险比：0.40，95%置信区间：0.19–0.86，对数秩检验p=0.0153）。结论：在台湾2型糖尿病患者中，TZD使用与MM风险临界性降低相关，该效应在≥65岁患者中更为显著。由于MM发病率较低，使用TZD预防MM可能不具备成本效益。TZD治疗患者可能存在生存优势。未来需进一步研究验证该发现。
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