Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands.
Ann Rheum Dis. 2024 Jan 11;83(2):161-168. doi: 10.1136/ard-2023-224814.
To study long-term (up to 20-year) mortality of two treat-to-target trial cohorts in undifferentiated arthritis (UA) and early rheumatoid arthritis (RA).
The BeSt (BehandelStrategieën) study (n=508, early RA) was performed between 2000 and 2012. For 10 years, patients were treated-to-target disease activity score (DAS)≤2.4.The Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease (IMPROVED) study (n=610, early RA/UA) was performed between 2007 and 2015. For 5 years, patients were treated-to-target DAS<1.6.Vital status of BeSt/IMPROVED participants was assessed up to and including 31 December 2021. Standardised mortality ratios (SMRs) were calculated. Stratified analyses for anticitrullinated protein antibody (ACPA) and smoking status were performed. Death causes and the potential effect of disease activity during the trial period on late mortality were assessed.
Excess mortality was found in both BeSt (SMR 1.32, 95% CI 1.14 to 1.53) and IMPROVED (SMR 1.33, 95% CI 1.10 to 1.63) and became manifest after 10 years. Excess mortality was statistically significant in ACPA+ patients who smoked (BeSt: SMR 2.80, 95% CI 2.16 to 3.64; IMPROVED: 2.14, 95% CI 1.33 to 3.45). Mean survival time was 10 (95% CI 5 to 16) months shorter than expected in BeSt and 13 (95% CI 11 to 16) months in IMPROVED. The HR for mortality was 1.34 (95% CI 0.96 to 1.86; BeSt)/1.13 (95% CI 0.67 to 1.91; IMPROVED) per 1 point increase in mean DAS during the trial. The main cause of death was malignancy.
After long-term treatment-to-target, excess mortality occurred in patients with RA after>10 years since treatment start, with smoking as an important risk factor.
研究两种针对目标的治疗试验队列在未分化关节炎（UA）和早期类风湿关节炎（RA）中的长期（长达 20 年）死亡率。
BeSt（治疗策略）研究（n=508，早期 RA）于 2000 年至 2012 年进行。10 年内，患者接受针对疾病活动评分（DAS）≤2.4 的治疗目标。Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease（IMPROVED）研究（n=610，早期 RA/UA）于 2007 年至 2015 年进行。5 年内，患者接受针对 DAS<1.6 的治疗目标。BeSt/IMPROVED 参与者的生存状况评估截至 2021 年 12 月 31 日。计算标准化死亡率比（SMR）。进行针对抗瓜氨酸蛋白抗体（ACPA）和吸烟状况的分层分析。评估了死因和试验期间疾病活动对晚期死亡率的潜在影响。
BeSt（SMR 1.32，95%CI 1.14 至 1.53）和 IMPROVED（SMR 1.33，95%CI 1.10 至 1.63）中均发现死亡率过高，且在 10 年后表现出来。在吸烟的 ACPA+患者中，死亡率过高具有统计学意义（BeSt：SMR 2.80，95%CI 2.16 至 3.64；IMPROVED：2.14，95%CI 1.33 至 3.45）。BeSt 的预期平均生存时间比预期短 10 个月（95%CI 5 至 16），IMPROVED 的预期平均生存时间短 13 个月（95%CI 11 至 16）。试验期间平均 DAS 每增加 1 点，死亡率的 HR 为 1.34（95%CI 0.96 至 1.86；BeSt）/1.13（95%CI 0.67 至 1.91；IMPROVED）。死亡的主要原因是恶性肿瘤。
在长期针对目标的治疗后，RA 患者在开始治疗>10 年后出现死亡率过高，吸烟是一个重要的危险因素。
