Effect of apremilast on hand and whole-body MRI assessments of inflammation in patients with psoriatic arthritis (MOSAIC): a phase 4, multicentre, single-arm, open-label study.
Mikkel Østergaard, Mikael Boesen, Walter P Maksymowych, Robert G Lambert, Michael R Bubb, Olga Kubassova, Guillermo Valenzuela, Jyotsna Reddy, Stephen Colgan, Yuri Klyachkin, Cynthia Deignan, Zhenwei Zhou, Hamid Amouzadeh, Philip J Mease
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引用次数: 0
Abstract
Background: The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE.
Methods: MOSAIC was a phase 4, multicentre, single-arm, open-label study conducted at 29 sites across ten countries (Belgium, Canada, Denmark, Germany, Italy, Russia, Spain, Switzerland, the UK, and the USA). Adults aged 18 years or older with a documented diagnosis of psoriatic arthritis for a duration of 3 months to 5 years self-enrolled and were included if they met the classification criteria for active psoriatic arthritis at screening. Patients were required to have at least three swollen and three tender joints with hand involvement and at least one active enthesitis site according to the Spondyloarthritis Research Consortium of Canada enthesitis index or the Leeds enthesitis index. Patients were excluded if they had previous treatment with a biological disease-modifying antirheumatic drug or previous treatment with more than two conventional synthetic disease-modifying antirheumatic drugs. After a 5-day titration period, patients received apremilast 30 mg orally twice per day. Concomitant stable methotrexate up to 25 mg per week was permitted. The primary endpoint was change from baseline to week 24 in a composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis in the hand as assessed by PsAMRIS. The full analysis set and safety population included all enrolled patients who received at least one dose of apremilast. This completed study is registered with ClinicalTrials.gov (NCT03783026).
Findings: Between Feb 6, 2019, and May 11, 2022, 123 patients were enrolled in the MOSAIC study. Of these 123 patients, 122 (99%) were treated with apremilast and included in the full analysis set and safety population. 67 (55%) of 122 patients were female, 55 (45%) were male, and 116 (95%) were White. 80 (66%) of 122 patients completed 48 weeks of treatment. The least squares mean change from baseline to week 24 in the composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis as assessed by PsAMRIS was -2·32 (95% CI -4·73 to 0·09). 95 (78%) of 122 patients had at least one treatment-emergent adverse event. Six (5%) patients had a severe treatment-emergent adverse event and six (5%) patients had a serious treatment-emergent adverse event. No serious treatment-emergent adverse events were considered to be related to apremilast.
Interpretation: Apremilast improved inflammation in joints and entheses on assessment of MRI measures in the hand and the whole body. Our findings encourage the use of MRI, including whole-body MRI, as an objective outcome measure in trials in patients with psoriatic arthritis.
背景:银屑病关节炎磁共振成像评分系统(PsAMRIS银屑病关节炎磁共振成像评分系统(PsAMRIS)和炎症性关节炎外周关节和内膜炎症核磁共振成像全身评分系统(MRI-WIPE)尚未在临床试验中同时用于评估银屑病关节炎的治疗。我们旨在通过PsAMRIS和MRI-WIPE测量结果,评估阿普司特治疗对炎症的影响:MOSAIC是一项4期、多中心、单臂、开放标签研究,在10个国家(比利时、加拿大、丹麦、德国、意大利、俄罗斯、西班牙、瑞士、英国和美国)的29个地点进行。年龄在18岁或18岁以上、被确诊患有银屑病关节炎3个月至5年的成人自行报名参加,如果他们在筛查时符合活动性银屑病关节炎的分类标准,则被纳入研究范围。根据加拿大脊柱关节炎研究联合会(Spondyloarthritis Research Consortium of Canada)的关节炎指数或利兹关节炎指数,患者必须至少有三个关节肿胀和三个关节触痛,且手部受累,并至少有一个活动性关节炎部位。如果患者曾接受过生物改善病情抗风湿药物治疗,或曾接受过两种以上传统合成改善病情抗风湿药物治疗,则排除在外。经过 5 天的滴定期后,患者开始口服阿普司特 30 毫克,每天两次。允许同时服用稳定的甲氨蝶呤,每周不超过25毫克。主要终点是PsAMRIS评估的手部骨髓水肿、滑膜炎和腱鞘炎综合炎症评分从基线到第24周的变化。完整的分析集和安全性人群包括所有接受了至少一次阿普司特治疗的入组患者。这项已完成的研究已在ClinicalTrials.gov(NCT03783026)上注册:2019年2月6日至2022年5月11日期间,MOSAIC研究共招募了123名患者。在这123名患者中,有122人(99%)接受了阿普司特治疗,并纳入了完整的分析集和安全人群。122名患者中有67名(55%)为女性,55名(45%)为男性,116名(95%)为白人。122名患者中有80名(66%)完成了48周的治疗。PsAMRIS评估的骨髓水肿、滑膜炎和腱鞘炎综合炎症评分从基线到第24周的最小二乘法平均变化为-2-32(95% CI -4-73至0-09)。122 名患者中有 95 人(78%)至少出现过一次治疗突发不良事件。6名患者(5%)发生了严重的治疗突发不良事件,6名患者(5%)发生了严重的治疗突发不良事件。没有严重治疗突发不良事件被认为与阿普司特有关:阿普瑞米司特改善了手部和全身核磁共振成像评估中关节和内膜的炎症。我们的研究结果鼓励将核磁共振成像(包括全身核磁共振成像)作为银屑病关节炎患者试验的客观结果测量指标:安进公司。
期刊介绍:
The Lancet Rheumatology, an independent journal, is dedicated to publishing content relevant to rheumatology specialists worldwide. It focuses on studies that advance clinical practice, challenge existing norms, and advocate for changes in health policy. The journal covers clinical research, particularly clinical trials, expert reviews, and thought-provoking commentary on the diagnosis, classification, management, and prevention of rheumatic diseases, including arthritis, musculoskeletal disorders, connective tissue diseases, and immune system disorders. Additionally, it publishes high-quality translational studies supported by robust clinical data, prioritizing those that identify potential new therapeutic targets, advance precision medicine efforts, or directly contribute to future clinical trials.
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