Katechis Spyridon, Pitsigavdaki Sofia, Nikoloudaki Myrto, Silvagni Ettore, Repa Argyro, Marangoni Antonio, Flouri Irini, Avgoustidis Nestor, Parperis Konstantinos, Govoni Marcello, Sidiropoulos Prodromos, Boumpas Dimitrios T, Fanouriakis Antonis, Bertsias George, Bortoluzzi Alessandra
Rheumatology and Clinical Immunology Unit, 4th Department of Internal Medicine, Attikon University Hospital, Joint Rheumatology Program, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Rheumatology and Clinical Immunology, University of Crete School of Medicine, Heraklion, Greece.
RMD Open. 2025 Jan 6;11(1):e005118. doi: 10.1136/rmdopen-2024-005118.
Glucocorticoid (GC) tapering and withdrawal to reduce damage represents a key aspect of the European Alliance of Associations for Rheumatology (EULAR) SLE recommendations. However, optimal strategies for relapse-free GC cessation remain ill-defined. We characterised clinical predictors and their combined effect on flares in patients with SLE who discontinued GC.
Retrospective cohort of 324 patients with active SLE (PGA ≥1.5 and/or SLEDAI-2K ≥6) who received GC as part of treatment intensification (median follow-up 60 months). Survival and generalised linear models estimated SELENA-SLEDAI flare risks and their predictors.
GCs were discontinued in 220 (67.9%) patients with 1-year risks for overall and severe flares of 50% and 25%, respectively (HR: 1.48; 95% CI: 1.12 to 1.96 for overall flares; HR: 1.52; 95% CI: 1.03 to 2.25 for severe flares, compared with non-withdrawers). Flare risk was lowered when GCs were ceased during remission (DORIS) or Lupus Low Disease Activity State (LLDAS; excluding remission) (HR for severe flares: 0.23; 0.12 to 0.43 and 0.30; 0.18 to 0.50, respectively), with each additional month in targets providing further protection. Hydroxychloroquine prevented total (HR: 0.37; 0.26 to 0.53) and severe flares (HR: 0.33; 0.21 to 0.52), while mycophenolate and azathioprine reduced overall flares. Prednisone tapering from 7.5 mg/day to 0 over >6 months improved severe flare-free outcome (HR: 0.57; 0.37 to 0.90). Random survival forests identified DORIS/LLDAS, hydroxychloroquine use and slow GC tapering as top predictors, whose coexistence reduced overall and severe flares by ~25 fold and ~50 fold, respectively. This combination reduced damage (IRR: 0.31; 0.08 to 0.84) without inducing flares (IRR: 0.52; 95% CI: 0.18 to 1.16) compared with GC non-withdrawers.
Low or absent disease activity, slow tapering and hydroxychloroquine use minimise the risk of flares, facilitating GC discontinuation-a major goal in SLE.
糖皮质激素（GC）减量和停用以减少损害是欧洲抗风湿病联盟（EULAR）系统性红斑狼疮（SLE）推荐的关键方面。然而，无复发的GC停药最佳策略仍不明确。我们对停用GC的SLE患者的临床预测因素及其对病情复发的综合影响进行了特征分析。
对324例活动期SLE患者（PGA≥1.5和/或SLEDAI - 2K≥6）进行回顾性队列研究，这些患者接受GC作为强化治疗的一部分（中位随访60个月）。生存模型和广义线性模型估计SELENA - SLEDAI病情复发风险及其预测因素。
220例（67.9%）患者停用GC，1年时总体病情复发风险和严重病情复发风险分别为50%和25%（总体病情复发的HR：1.48；95%CI：1.12至1.96；严重病情复发的HR：1.52；95%CI：1.03至2.25，与未停药者相比）。在病情缓解期（DORIS）或狼疮低疾病活动状态（LLDAS，不包括缓解期）停用GC时，病情复发风险降低（严重病情复发的HR分别为：0.23；0.12至0.43和0.30；0.18至0.50），在目标状态下每多一个月可提供进一步保护。羟氯喹预防总体病情复发（HR：0.37；0.26至0.53）和严重病情复发（HR：0.33；0.21至0.52），而霉酚酸酯和硫唑嘌呤减少总体病情复发。泼尼松在>6个月内从7.5mg/天减至0可改善无严重病情复发的结局（HR：0.57；0.37至0.90）。随机生存森林分析确定DORIS/LLDAS、使用羟氯喹和缓慢减量GC为主要预测因素，它们同时存在可使总体病情复发和严重病情复发分别降低约25倍和约50倍。与未停用GC者相比，这种组合减少了损害（IRR：0.31；0.08至0.84）且未诱发病情复发（IRR：0.52；95%CI：0.18至1.16）。
低疾病活动度或无疾病活动度、缓慢减量和使用羟氯喹可将病情复发风险降至最低，有助于GC停用——这是SLE治疗的一个主要目标。
