Department of Medicine, Sub-Faculty of Clinical and Molecular Medicine, Monash University, Melbourne, VIC, Australia.
Department of Medicine, Sub-Faculty of Clinical and Molecular Medicine, Monash University, Melbourne, VIC, Australia.
Lancet Rheumatol. 2024 Aug;6(8):e528-e536. doi: 10.1016/S2665-9913(24)00121-8. Epub 2024 Jun 11.
Validation of protective associations of the lupus low disease activity state (LLDAS) against flare, irreversible damage, health-related quality of life, and mortality has enabled the adoption of treat-to-target strategies in patients with systemic lupus erythematosus (SLE). Previous validation studies were of short duration, limiting the ability to detect longer term signals in flare rate and irreversible damage. In addition, previous studies have focused on percent time at target, rather than actual periods of time that are more useful in clinical practice and trials. We assessed long-term protective associations of LLDAS and remission, and specifically examined protective thresholds of sustained LLDAS and remission.
Patients aged 18 years or older with SLE were followed up from May 1, 2013, to Dec 31, 2020 in a prospective, multinational, longitudinal cohort study. Patients were recruited from 25 centres in 12 countries. Multi-failure time-to-event analyses were used to assess the effect of sustained LLDAS on irreversible damage accrual (primary outcome; measured with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) and flare (key secondary outcome; measured with the SELENA Flare Index), with dose exposure and threshold effects studied. Sustained LLDAS or remission were defined as two or more consecutive visits over at least 3 months in the respective state. This study is registered with ClinicalTrials.gov, NCT03138941.
3449 patients were followed up for a median of 2·8 years (IQR 1·1-5·6), totalling 37 662 visits. 3180 (92·2%) patients were women, and 3031 (87·9%) were of Asian ethnicity. 2506 (72·7%) patients had sustained LLDAS at least once. Any duration of sustained LLDAS or remission longer than 3 months was associated with reduced damage accrual (LLDAS: hazard ratio 0·60 [95% CI 0·51-0·71], p<0·0001; remission: 0·66 [0·57-0·76], p<0·0001) and flare (LLDAS: 0·56 [0·51-0·63], p<0·0001; remission: 0·66 [0·60-0·73], p<0·0001), and increasing durations of sustained LLDAS corresponded to increased protective associations. Sustained DORIS remission or steroid-free remission were less attainable than LLDAS.
We observed significant protective associations of LLDAS and remission against damage accrual and flare, establish a threshold of 3 months sustained LLDAS or remission as protective, and demonstrate deepening protection with longer durations of sustained LLDAS or remission.
The Asia Pacific Lupus Collaboration receives project support grants from AstraZeneca, Bristol Myers Squibb, EMD Sereno, GSK, Janssen, Eli Lilly, and UCB.
狼疮低疾病活动状态（LLDAS）与狼疮患者复发、不可逆转的损害、健康相关的生活质量和死亡率之间的保护关联已得到验证，这使得在系统性红斑狼疮（SLE）患者中采用靶向治疗策略成为可能。以前的验证研究持续时间较短，限制了在复发率和不可逆转损害方面检测更长期信号的能力。此外，以前的研究侧重于目标的百分比时间，而不是在临床实践和试验中更有用的实际时间段。我们评估了 LLDAS 和缓解的长期保护关联，并特别研究了持续 LLDAS 和缓解的保护阈值。
2013 年 5 月 1 日至 2020 年 12 月 31 日，在一项前瞻性、多中心、纵向队列研究中对年龄在 18 岁及以上的 SLE 患者进行了随访。患者来自 12 个国家的 25 个中心招募。采用多失效时间事件分析评估持续 LLDAS 对不可逆转损害累积（主要结局；用系统性红斑狼疮国际合作临床/美国风湿病学会损害指数测量）和复发（关键次要结局；用 SELENA 复发指数测量）的影响，并研究了剂量暴露和阈值效应。持续的 LLDAS 或缓解定义为在各自状态下至少连续两次连续就诊至少 3 个月。本研究在 ClinicalTrials.gov 注册，NCT03138941。
3449 名患者的中位随访时间为 2.8 年（IQR 1.1-5.6），共随访 37662 次。3180 名（92.2%）患者为女性，3031 名（87.9%）为亚洲人。2506 名（72.7%）患者至少有一次持续 LLDAS。持续 LLDAS 或缓解时间超过 3 个月与损害累积减少有关（LLDAS：风险比 0.60 [95%CI 0.51-0.71]，p<0.0001；缓解：0.66 [0.57-0.76]，p<0.0001）和复发（LLDAS：0.56 [0.51-0.63]，p<0.0001；缓解：0.66 [0.60-0.73]，p<0.0001），持续 LLDAS 时间越长，保护作用越强。持续 DORIS 缓解或无激素缓解比 LLDAS 更难达到。
我们观察到 LLDAS 和缓解与损害累积和复发之间存在显著的保护关联，确定了 3 个月持续 LLDAS 或缓解的保护阈值，并证明了持续 LLDAS 或缓解时间的延长会加深保护作用。
亚太狼疮协作组织从阿斯利康、百时美施贵宝、EMD Sereno、GSK、杨森、礼来和 UCB 获得项目支持赠款。
