Differences in biologic dose-escalation, non-biologic and steroid intensification among three anti-TNF agents: evidence from clinical practice.

Moots RJ, Haraoui B, Matucci-Cerinic M, van Riel PL, Kekow J, Schaeverbeke T, Davis A, Tedeschi MA, Freundlich B, Chang DJ, Singh A.

University of Liverpool Academic Rheumatology Unit, University Hospital Aintree, Liverpool, UK. rjmoots@liv.ac.uk.

Abstract

OBJECTIVES: To evaluate prevalence of dose escalation among RA patients in normal clinical practice treated with etanercept, adalimumab or infliximab and to estimate its economic impact.

METHODS: A retrospective observational study of 739 patients with RA receiving continuous treatment with etanercept (n=319), adalimumab (n=313) or infliximab (n=107) for 18 months. Dose escalation, intensification of concomitant DMARDs and risk of dose escalation were evaluated, as well as costs.

RESULTS: Significantly more patients prescribed adalimumab (10%, p<0.001) or infliximab (35%, p<0.001) experienced dose escalation compared with patients treated with etanercept (3%). DMARD or steroid dose adjustment, when added as criteria of escalation, occurred more often among patients treated with adalimumab (28%; p=0.022) or infliximab (47%; p<0.001) than those prescribed etanercept (19%). Independent of confounding covariates, hazard of dose escalation was significantly higher for either infliximab (28.1-fold) or adalimumab (4.9-fold) relative to etanercept. Escalation among subjects treated with either infliximab or adalimumab incurred statistically significant increases in total cost of care compared with non-escalators whereas such differences observed for subjects treated with etanercept were not significant.

CONCLUSIONS: Patients receiving monoclonal antibody therapies, adalimumab or infliximab, had significantly higher rates of dose escalation than patients receiving the soluble TNF receptor, etanercept, and related costs were higher.

三种anti-TNF制剂生物学剂量增加、非生物制剂和类固醇强化作用的差异：来自临床实践的证据

目的:评价日常临床实践中应用依那西普、英夫利昔单抗或阿达木单抗治疗类风湿关节炎患者时剂量增加的发生率,评价其对经济的影响。

方法:对739例接受依那西普(n = 319)、阿达木单抗(n = 313)或英夫利昔单抗(n = 107) 连续治疗18个月的RA患者进行回顾性观察研究。对生物制剂剂量增加、合并DMARDs的强化治疗、剂量增加的风险以及成本进行了评估。

结果:接受阿达木单抗 (10%，p < 0.001)或英夫利昔单抗(35%,p < 0.001) 治疗的患者比依那西普(3%)治疗的患者，剂量增加的比例显著增高。DMARD或类固醇剂量增加的比例在阿达木单抗组(28%;p = 0.022)或英夫利昔单抗组(47%,p < 0.001)更多见，依那西普组为19%。独立的混杂因素中，剂量增加的风险无论是英夫利昔单抗 (28.1倍 )或阿达木单抗(4.9倍)都要明显高于依那西普。英夫利昔单抗或阿达木单抗治疗中剂量增加的患者，其治疗费用明显高于剂量未增加的患者，而依那西普治疗患者中这种差异不明显。

结论:接受单克隆抗体治疗的患者中,阿达木单抗或英夫利昔单抗剂量增加的比例明显高于可溶性TNF受体依那西普，由此相关的成本也更高。