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早期启用贝利尤单抗改善系统性红斑狼疮治疗结局:来自一项多中心回顾性研究头五年的见解

Enhancing systemic lupus erythematosus treatment outcomes with an early initiation of belimumab: insights from a multicenter retrospective study within the first five years.

作者信息

Kojima Kanako, Ichinose Kunihiro, Umeda Masataka, Shimizu Toshimasa, Sato Shuntaro, Suzuki Takahisa, Nakashima Yoshikazu, Okada Akitomo, Horai Yoshiro, Fujikawa Keita, Aramaki Toshiyuki, Miyashita Taiichiro, Furuyama Masako, Matsuoka Naoki, Kawakami Atsushi

机构信息

Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Department of Rheumatology, Faculty of Medicine, Shimane University, 89-1 Enya-Cho, Izumo, 693-8501, Japan.

出版信息

Arthritis Res Ther. 2025 May 29;27(1):116. doi: 10.1186/s13075-025-03581-0.

Abstract

BACKGROUND

The human monoclonal antibody belimumab (BEL) has emerged as a promising treatment for systemic lupus erythematosus (SLE), particularly for reducing the need for glucocorticoids and minimizing organ damage. The optimal timing of BEL initiation has been unclear; emerging evidence suggests that early intervention with BEL, particularly within the first 5 years of diagnosis, may yield better outcomes by modulating disease progression and reducing flare frequency. Understanding the relationship between disease duration and BEL efficacy is essential for the development of tailored strategies.

PATIENTS AND METHODS

We analyzed patients with SLE treated at our hospital and associated facilities who were diagnosed according to the 1997 ACR or 2012 SLICC criteria and who began BEL treatment between December 2017 and August 2021. Patients who were followed for ≥ 12 months after BEL initiation were included. We investigated the changes in the patients' Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores at 3, 6, 9, and 12 months after the introduction of BEL, comparing patients with disease durations ≤ 5 years to those with > 5 years. A mixed-effects model was adjusted for the patients' ages, prednisolone dosages, initial SELENA-SLEDAI scores, Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI), hydroxychloroquine use, and lupus nephritis. Clinical manifestations including arthritis, skin lesions, and hematological abnormalities were monitored to assess the broader impacts of BEL.

RESULTS

One hundred eleven patients were initially registered; among them, 97 patients were included in the final analysis. The study population (mean age, 41 years; mean SELENA-SLEDAI, 7 points; 51% using hydroxychloroquine) included 19 patients with a ≤ 5-year SLE duration and 78 with SLE durations > 5 years. The baseline SELENA-SLEDAI scores were higher in the ≤ 5-year group (p = 0.047), indicating more active disease. Patients with ≤ 5 years of disease had significantly greater improvements in SELENA-SLEDAI scores at 6, 9, and 12 months (p < 0.05).

CONCLUSIONS

These results highlight the importance of early BEL initiation in SLE, demonstrating that patients with shorter disease durations achieve more substantial improvements in disease activity with early BEL treatment. Our findings also reveal the potential benefits of early BEL intervention and suggest that incorporating the disease duration into treatment decisions may optimize patient outcomes.

摘要

背景

人源单克隆抗体贝利尤单抗(BEL)已成为系统性红斑狼疮(SLE)一种有前景的治疗方法,尤其在减少糖皮质激素需求和使器官损害最小化方面。贝利尤单抗开始治疗的最佳时机尚不清楚;新出现的证据表明,早期使用贝利尤单抗进行干预,特别是在诊断后的前5年内,可能通过调节疾病进展和减少发作频率而产生更好的结果。了解疾病持续时间与贝利尤单抗疗效之间的关系对于制定个性化策略至关重要。

患者和方法

我们分析了在我院及相关机构接受治疗的SLE患者,这些患者根据1997年美国风湿病学会(ACR)或2012年系统性红斑狼疮国际协作临床工作组(SLICC)标准进行诊断,并于2017年12月至2021年8月开始接受贝利尤单抗治疗。纳入在开始使用贝利尤单抗后随访≥12个月的患者。我们调查了开始使用贝利尤单抗后3、6、9和12个月时患者的雌激素在狼疮中的安全性-系统性红斑狼疮疾病活动指数(SELENA-SLEDAI)评分的变化,将疾病持续时间≤5年的患者与疾病持续时间>5年的患者进行比较。采用混合效应模型对患者的年龄、泼尼松龙剂量、初始SELENA-SLEDAI评分、系统性红斑狼疮国际协作临床工作组(SLICC)损伤指数(SDI)、羟氯喹使用情况和狼疮性肾炎进行校正。监测包括关节炎、皮肤病变和血液学异常在内的临床表现,以评估贝利尤单抗的更广泛影响。

结果

最初登记了111例患者;其中,97例患者纳入最终分析。研究人群(平均年龄41岁;平均SELENA-SLEDAI评分为7分;51%使用羟氯喹)包括19例SLE病程≤5年的患者和78例SLE病程>5年的患者。病程≤5年组的基线SELENA-SLEDAI评分更高(p = 0.047),表明疾病更活跃。病程≤5年的患者在6、9和12个月时SELENA-SLEDAI评分改善更显著(p<0.05)。

结论

这些结果突出了在SLE中早期开始使用贝利尤单抗的重要性,表明病程较短的患者通过早期贝利尤单抗治疗在疾病活动度方面取得更显著的改善。我们的研究结果还揭示了早期贝利尤单抗干预的潜在益处,并表明将疾病持续时间纳入治疗决策可能会优化患者的治疗结果。

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