Global Health Economics, Amgen, Inc., Thousand Oaks, CA 91320, USA.
Curr Med Res Opin. 2010 Jul;26(7):1637-45. doi: 10.1185/03007995.2010.483127.
Tumor necrosis factor (TNF) antagonists, most frequently prescribed biologics for moderate to severe rheumatoid arthritis (RA), are subject to dose escalation. Even though different methods have been employed to estimate the timing and magnitude of dose escalation, there is no consensus on which method is optimal. The purpose was to evaluate different methods for assessing dose escalation patterns for the subcutaneously delivered TNF antagonists, etanercept and adalimumab.
Five different methods to describe dose escalation patterns were compared using a large administrative claims database from US health plans. RA patients age 18 and above with >or=2 claims for etanercept or adalimumab were included. These methods included last dose versus index dose (the dose of a patient's first biologic prescription [adalimumab or etanercept]), average dose versus recommended dose, multiple (>or=2) instances of subsequent doses exceeding the index dose, subsequent doses exceeding a predetermined threshold above the index dose, and the time-trend method, comparing each subsequent dose throughout the course of therapy to the index dose.
A total of 1369 etanercept and 461 adalimumab RA patients were evaluated for dose escalation. Estimates of dose escalation were highest for both drugs based on the average dose method (10.3% for etanercept, 33.6% for adalimumab). The time-trend method demonstrated the temporal trends in the percent of patients with dose escalation. Adalimumab patients had a higher rate of dose escalation than etanercept patients, regardless of method. The study is limited in that it could not assess the reason for or clinical outcomes associated with dose escalation.
Different methods for evaluating dose escalation yield different numerical estimates but consistently give the same overall comparative result. The choice of method should depend on the specific research question. The average dose method may be the most useful for cost impact studies, whereas the time-trend method provides the most comprehensive information on dose patterns.
肿瘤坏死因子（TNF）拮抗剂是治疗中重度类风湿关节炎（RA）最常使用的生物制剂，通常需要进行剂量递增。尽管已经采用了不同的方法来估计剂量递增的时间和幅度，但哪种方法最佳尚无共识。本研究旨在评估皮下给予 TNF 拮抗剂依那西普和阿达木单抗时评估剂量递增模式的不同方法。
使用美国健康计划的大型行政索赔数据库，比较了描述剂量递增模式的 5 种不同方法。纳入年龄≥18 岁且有≥2 次依那西普或阿达木单抗用药记录的 RA 患者。这些方法包括末次剂量与起始剂量（患者首次使用生物制剂[阿达木单抗或依那西普]的剂量）、平均剂量与推荐剂量、后续剂量≥起始剂量 2 次以上、后续剂量超过起始剂量预定阈值以及时间趋势法，即比较整个治疗过程中每次后续剂量与起始剂量的差异。
共有 1369 例依那西普和 461 例阿达木单抗 RA 患者被评估剂量递增。基于平均剂量法，两种药物的剂量递增估计值均最高（依那西普为 10.3%，阿达木单抗为 33.6%）。时间趋势法显示了剂量递增患者的百分比的时间趋势。无论采用哪种方法，阿达木单抗患者的剂量递增率均高于依那西普患者。本研究的局限性在于无法评估剂量递增的原因或与剂量递增相关的临床结局。
不同的剂量递增评估方法产生不同的数值估计值，但总体上给出了相同的比较结果。方法的选择应取决于具体的研究问题。平均剂量法可能最适用于成本影响研究，而时间趋势法提供了关于剂量模式的最全面信息。
