Sandino-Bermúdez Marlon J, Hernández-Molina Gabriela
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Col. Belisario Domínguez Sección XVI, CP 14080 Mexico City, Mexico.
Joint Bone Spine. 2025 Jan;92(1):105799. doi: 10.1016/j.jbspin.2024.105799. Epub 2024 Oct 28.
About 25-50% of patients with primary Sjögren's disease (SjD) take hydroxychloroquine (HCQ). Although it is widely prescribed, and recommended in international guidelines, its use is mostly based on expert opinion and personal experience. Our aim was to provide a comprehensive overview of the pathogenic mechanisms of HCQ, the current clinical evidence for its use, and its safety in primary SjD. HCQ plays an immunomodulatory and anti-inflammatory role, mainly by regulating some interferon proteins, chemokines, BAFF levels, and by modifying gut microbiota. It decreases immunoglobulins and ESR levels. In a Latin-American cohort, the main indications were arthritis, parotid gland enlargement and sicca-only symptoms. In the clinical setting, most studies showing a positive effect of HQC are open trials or retrospective cohorts. Some of these studies may be biased due to the use of non-validated outcomes, and a placebo response effect. To date, only 3 RCTs have investigated the benefits of HCQ, the JOQUER being the pivotal one. This study failed to improve oral/ocular symptoms or ESSDAI score. However, a re-analysis by symptomatology subgroups detected some differences in the ESSPRI. Recently, promising data from a small phase II RCT of the combination of HCQ/leflunomide was reported, but results should be replicated. Currently, the NECESSITY study is investigating treatment combinations that will provide new insights. In the meantime, HCQ plays a central role in the treatment of SjD due to its excellent benefit-risk profile. Data on damage accrual, quality of life, mortality and prevention of cardiovascular risks are also still lacking.
约25%-50%的原发性干燥综合征（SjD）患者服用羟氯喹（HCQ）。尽管该药被广泛处方并在国际指南中得到推荐，但其使用大多基于专家意见和个人经验。我们的目的是全面概述HCQ的致病机制、目前使用该药的临床证据及其在原发性SjD中的安全性。HCQ发挥免疫调节和抗炎作用，主要通过调节某些干扰素蛋白、趋化因子、B淋巴细胞刺激因子（BAFF）水平以及改变肠道微生物群。它可降低免疫球蛋白和红细胞沉降率（ESR）水平。在一个拉丁美洲队列中，主要适应证为关节炎、腮腺肿大和仅存在干燥症状。在临床实践中，大多数显示HCQ有积极作用的研究都是开放试验或回顾性队列研究。其中一些研究可能因使用未经验证的结局指标和安慰剂反应效应而存在偏倚。迄今为止，仅有3项随机对照试验（RCT）研究了HCQ的益处，其中“JOQUER”试验是关键试验。该研究未能改善口腔/眼部症状或欧洲抗风湿病联盟疾病活动指数（ESSDAI）评分。然而，按症状亚组进行的重新分析在欧洲干燥综合征患者报告指数（ESSPRI）方面发现了一些差异。最近，有报道称一项关于HCQ/来氟米特联合用药的小型II期RCT取得了有前景的数据，但结果需要重复验证。目前，“必要性”研究正在调查能提供新见解的治疗组合。与此同时，由于HCQ具有良好的效益风险比，它在SjD的治疗中发挥着核心作用。关于损伤累积、生活质量、死亡率和心血管风险预防的数据也仍然缺乏。
