Dörner Thomas, Bowman Simon J, Fox Robert, Mariette Xavier, Papas Athena, Grader-Beck Thomas, Fisher Benjamin A, Barcelos Filipe, De Vita Salvatore, Schulze-Koops Hendrik, Moots Robert J, Junge Guido, Woznicki Janice, Sopala Monika, Avrameas Alexandre, Luo Wen-Lin, Hueber Wolfgang
Charite Universitätsmedizin, Berlin, Germany.
University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
Arthritis Rheumatol. 2025 May;77(5):560-570. doi: 10.1002/art.43059. Epub 2025 Jan 5.
The objective of this study was to report 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren's disease (SjD).
Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks until week 24 (treatment period [TP]1). At week 24, patients on 300 mg were rerandomized to continue 300 mg or receive placebo until week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, and patients on 5 and 50 mg directly entered posttreatment safety follow-up. Patients who discontinued treatment early or completed treatment entered safety follow-up (≥20 weeks).
During TP1, 190 patients were randomized (placebo = 49, 5 mg = 47, 50 mg = 47, 300 mg = 47). Of these 190 patients, 90 (47.4 %; 43 continued 300 mg and 47 received placebo) entered TP2, and 81 of 90 (90.0%) completed the study treatment. By week 52, efficacy was sustained in patients who continued 300 mg in TP2 (EULAR Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index, patient global assessment, and physician global assessment change from week 24: -1.45, -0.46, -4.69, and -6.86, respectively). Stimulated salivary flow rates and autoantibody levels numerically improved in the 300 mg group. Treatment-emergent adverse events were not dose-dependent, except for injection-site reactions. Cases of decreased neutrophil counts (Common Terminology Criteria for Adverse Events v4.03 grade 3 according to laboratory listings) were observed in three patients during the posttreatment follow-up, occurring at 3.5, 5.5, and 3 months, after the last ianalumab administration. None were associated with infection except one incidental finding of asymptomatic cytomegalovirus infection (IgM-positive).
In patients with SjD, ianalumab 300 mg demonstrated sustained efficacy through week 52 and a favorable safety profile up to two years of follow-up.
本研究旨在报告在干燥综合征（SjD）患者中进行的2b期剂量探索性研究中，伊那鲁单抗52周的安全性和有效性。
患者按1:1:1:1随机分组，每4周皮下注射伊那鲁单抗（5、50或300mg）或安慰剂，直至第24周（治疗期[TP]1）。在第24周时，接受300mg治疗的患者重新随机分组，继续接受300mg治疗或接受安慰剂直至第52周（TP2），接受安慰剂治疗的患者换用150mg伊那鲁单抗，接受5mg和50mg治疗的患者直接进入治疗后安全性随访。提前停药或完成治疗的患者进入安全性随访（≥20周）。
在TP1期间，190例患者被随机分组（安慰剂组=49例，5mg组=47例，50mg组=47例，300mg组=47例）。在这190例患者中，90例（47.4%；43例继续接受300mg治疗，47例接受安慰剂）进入TP2，90例中的81例（90.0%）完成了研究治疗。到第52周时，TP2中继续接受300mg治疗的患者疗效得以维持（欧洲抗风湿病联盟干燥综合征疾病活动指数、欧洲抗风湿病联盟干燥综合征患者报告指数、患者整体评估和医生整体评估较第24周的变化分别为-1.45、-0.46、-4.69和-6.86）。300mg组的刺激唾液流速和自身抗体水平在数值上有所改善。除注射部位反应外，治疗中出现的不良事件与剂量无关。在治疗后随访期间，3例患者出现中性粒细胞计数减少（根据实验室清单，不良事件通用术语标准v4.03为3级），发生在最后一次注射伊那鲁单抗后的3.5、5.5和3个月。除1例偶然发现的无症状巨细胞病毒感染（IgM阳性）外，均与感染无关。
在SjD患者中，300mg伊那鲁单抗在第52周时显示出持续疗效，在长达两年的随访中安全性良好。
