Ytterberg SR et al.N Engl J Med. 2022 Jan 27;386(4):316-326. 

与使用肿瘤坏死因子(TNF)抑制剂的类风湿关节炎患者相比，使用托法替尼（Tofacitinib）治疗患者的脂质水平升高和癌症是否发生改变目前尚不清楚。该研究是一项不良心血管事件(MACE)和癌症的试验分析。

该项研究纳入4362例患者，分为3组，托法替尼治疗（n=1455，5mg），托法替尼治疗（n=1455，10mg），TNF抑制剂治疗（n=1451），4年随访数据中托法替尼的MACE和癌症发生率(分别为3.4%和4.2%)高于TNF抑制剂(2.5%和2.9%)。MACE的风险比为1.33(95%CI， 0.91 ~ 1.94)，癌症的风险比为1.48 (95% CI, 1.04 ~ 2.09)。

研究在心血管风险高的人群中进行比较托法替尼联合剂量与TNF抑制剂的患者结局，数据结果显示托法替尼的MACE和癌症风险更高，不良事件更为常见。

Background: Increases in lipid levels and cancers with tofacitinib prompted a trial of major adverse cardiovascular events (MACE) and cancers in patients with rheumatoid arthritis receiving tofacitinib as compared with a tumor necrosis factor (TNF) inhibitor.

Methods: We conducted a randomized, open-label, noninferiority, postauthorization, safety end-point trial involving patients with active rheumatoid arthritis despite methotrexate treatment who were 50 years of age or older and had at least one additional cardiovascular risk factor. Patients were randomly assigned in a 1:1:1 ratio to receive tofacitinib at a dose of 5 mg or 10 mg twice daily or a TNF inhibitor. The coprimary end points were adjudicated MACE and cancers, excluding nonmelanoma skin cancer. The noninferiority of tofacitinib would be shown if the upper boundary of the two-sided 95% confidence interval for the hazard ratio was less than 1.8 for the combined tofacitinib doses as compared with a TNF inhibitor.

Results: A total of 1455 patients received tofacitinib at a dose of 5 mg twice daily, 1456 received tofacitinib at a dose of 10 mg twice daily, and 1451 received a TNF inhibitor. During a median follow-up of 4.0 years, the incidences of MACE and cancer were higher with the combined tofacitinib doses (3.4% [98 patients] and 4.2% [122 patients], respectively) than with a TNF inhibitor (2.5% [37 patients] and 2.9% [42 patients]). The hazard ratios were 1.33 (95% confidence interval [CI], 0.91 to 1.94) for MACE and 1.48 (95% CI, 1.04 to 2.09) for cancers; the noninferiority of tofacitinib was not shown. The incidences of adjudicated opportunistic infections (including herpes zoster and tuberculosis), all herpes zoster (nonserious and serious), and adjudicated nonmelanoma skin cancer were higher with tofacitinib than with a TNF inhibitor. Efficacy was similar in all three groups, with improvements from month 2 that were sustained through trial completion.

Conclusions: In this trial comparing the combined tofacitinib doses with a TNF inhibitor in a cardiovascular risk-enriched population, risks of MACE and cancers were higher with tofacitinib and did not meet noninferiority criteria. Several adverse events were more common with tofacitinib. (Funded by Pfizer; ORAL Surveillance ClinicalTrials.gov number, NCT02092467.).

百度浏览   来源 : 医微客   

版权声明：本网站所有注明来源“医微客”的文字、图片和音视频资料，版权均属于医微客所有，非经授权，任何媒体、网站或个人不得转载，授权转载时须注明来源：”医微客”。本网所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，转载仅作观点分享，版权归原作者所有。不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。 本站拥有对此声明的最终解释权。