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司库奇尤单抗对放射性轴性脊柱关节炎患者的非甾体抗炎药节省效应:MEASURE 2、3和4项III期试验的4年结果

Nonsteroidal anti-inflammatory drug-sparing effect of secukinumab in patients with radiographic axial spondyloarthritis: 4-year results from the MEASURE 2, 3 and 4 phase III trials.

作者信息

Dougados Maxime, Kiltz Uta, Kivitz Alan, Pavelka Karel, Rohrer Susanne, McCreddin Suzanne, Quebe-Fehling Erhard, Porter Brian, Talloczy Zsolt

机构信息

Department of Rheumatology, Université de Paris, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.

INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France.

出版信息

Rheumatol Int. 2022 Feb;42(2):205-213. doi: 10.1007/s00296-021-05044-6. Epub 2021 Nov 13.

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain and inflammation, and are considered the cornerstone of pharmacological intervention in patients with radiographic axial spondyloarthritis (r-axSpA); however, the long-term use of NSAIDs is debatable due to their restricted therapeutic potential and the risk of side effects and complications. Therefore, reduction in NSAID intake is desirable in r-axSpA patients. Here, we report the long-term NSAID-sparing effect of secukinumab over 4 years in patients with r-axSpA. This post hoc analysis pooled data from 3 secukinumab trials (MEASURE 2-4) for each secukinumab maintenance dose of 150 and 300 mg, regardless of the loading dose regimen being i.v. or s.c. NSAID intake was evaluated prospectively using the Assessment of SpondyloArthritis International Society (ASAS)-NSAID score. Patients with an ASAS-NSAID score > 0 at baseline were analysed. NSAID-sparing endpoints included the mean change in the ASAS-NSAID score, the proportion of patients achieving 50% reduction, and the proportion of patients with an ASAS-NSAID score < 10. Percentages of patients who achieved BASDAI ≤ 2 were also assessed. Overall, 562 patients were included in this pooled analysis (secukinumab: 150 mg, N = 467; 300 mg, N = 95). The mean ASAS-NSAID score decreased with time in both the secukinumab 150 mg and 300 mg dose groups. The proportion of patients who achieved 50% reduction in the ASAS-NSAID score and clinically meaningful reduction of ASAS-NSAID score < 10 increased with time in both dose groups and in both low and high NSAID intake patients. The percentage of patients with a clinically relevant improvement (BASDAI ≤ 2) was consistently higher in patients with an ASAS-NSAID score < 10 than in patients with an ASAS-NSAID score ≥ 10. Secukinumab provided sustained, long-term NSAID-sparing effects in patients with r-axSpA for up to 4 years of treatment, as measured using the ASAS-NSAID score. Trial registered at clinicaltrials.gov: NCT01649375 ( https://clinicaltrials.gov/ct2/show/NCT01649375 ); NCT02008916 ( https://clinicaltrials.gov/ct2/show/NCT02008916 ); NCT02159053 ( https://clinicaltrials.gov/ct2/show/NCT02159053 ).

摘要

非甾体抗炎药(NSAIDs)常用于减轻疼痛和炎症,被认为是影像学轴向脊柱关节炎(r-axSpA)患者药物干预的基石;然而,由于其有限的治疗潜力以及副作用和并发症风险,NSAIDs的长期使用存在争议。因此,r-axSpA患者减少NSAID摄入量是可取的。在此,我们报告了司库奇尤单抗在r-axSpA患者中超过4年的长期NSAID节省效应。这项事后分析汇总了3项司库奇尤单抗试验(MEASURE 2 - 4)的数据,针对司库奇尤单抗的每种维持剂量150和300mg,无论负荷剂量方案是静脉注射还是皮下注射。使用国际脊柱关节炎评估协会(ASAS)-NSAID评分前瞻性评估NSAID摄入量。分析了基线时ASAS-NSAID评分>0的患者。NSAID节省终点包括ASAS-NSAID评分的平均变化、实现降低50%的患者比例以及ASAS-NSAID评分<10的患者比例。还评估了达到BASDAI≤2的患者百分比。总体而言,562例患者纳入了这项汇总分析(司库奇尤单抗:150mg,N = 467;300mg,N = 95)。在司库奇尤单抗150mg和300mg剂量组中,ASAS-NSAID评分均随时间下降。在两个剂量组以及低和高NSAID摄入量患者中,ASAS-NSAID评分降低50%且临床上有意义的降低(ASAS-NSAID评分<10)的患者比例随时间增加。ASAS-NSAID评分<10的患者中临床相关改善(BASDAI≤2)的百分比始终高于ASAS-NSAID评分≥10的患者。使用ASAS-NSAID评分衡量,司库奇尤单抗在r-axSpA患者中提供了长达4年治疗期的持续、长期NSAID节省效应。试验在clinicaltrials.gov注册:NCT01649375(https://clinicaltrials.gov/ct2/show/NCT01649375);NCT02008916(https://clinicaltrials.gov/ct2/show/NCT02008916);NCT02159053(https://clinicaltrials.gov/ct2/show/NCT02159053)。

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