Østergaard Mikkel, Boesen Mikael, Maksymowych Walter P, Lambert Robert G, Bubb Michael R, Kubassova Olga, Valenzuela Guillermo, Reddy Jyotsna, Colgan Stephen, Klyachkin Yuri, Deignan Cynthia, Zhou Zhenwei, Amouzadeh Hamid, Mease Philip J
Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Department of Radiology, Copenhagen University Hospital, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
Lancet Rheumatol. 2025 Feb;7(2):e118-e126. doi: 10.1016/S2665-9913(24)00232-7. Epub 2024 Oct 30.
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.
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).
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.
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.
Amgen.
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及附着点炎症的MRI全身评分系统（MRI-WIPE）尚未在一项临床试验中联合用于评估银屑病关节炎的治疗。我们旨在评估阿普斯特治疗对炎症的影响，采用PsAMRIS和MRI-WIPE测量结果。
MOSAIC是一项4期、多中心、单臂、开放标签研究，在十个国家（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岁及以上、有银屑病关节炎确诊记录且病程为3个月至5年的成年人自行报名，若在筛查时符合活动性银屑病关节炎的分类标准则纳入研究。根据加拿大脊柱关节炎研究联盟附着点炎指数或利兹附着点炎指数，患者需至少有三个肿胀和三个压痛关节且手部受累，以及至少一个活动性附着点炎部位。若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，患者每天口服两次阿普斯特30mg。允许同时使用稳定剂量的甲氨蝶呤，每周最多25mg。主要终点是通过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。完整分析集和安全人群包括所有接受至少一剂阿普斯特的入组患者。这项完成的研究已在ClinicalTrials.gov（NCT03783026）注册。
在2019年2月6日至2022年5月11日期间，123名患者纳入了MOSAIC研究。在这123名患者中，122名（99%）接受了阿普斯特治疗并纳入完整分析集和安全人群。122名患者中67名（55%）为女性，55名（45%）为男性，116名（95%）为白人。122名患者中80名（66%）完成了48周的治疗。通过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周的最小二乘均值变化为-2.32（95%CI -4.73至0.09）。122名患者中有95名（78%）至少发生了一次治疗中出现的不良事件。6名（5%）患者发生了严重治疗中出现的不良事件，6名（5%）患者发生了严重的治疗中出现的不良事件。没有严重治疗中出现的不良事件被认为与阿普斯特有关。
在对手部和全身的MRI测量评估中，阿普斯特改善了关节和附着点的炎症。我们的研究结果鼓励在银屑病关节炎患者的试验中使用MRI，包括全身MRI，作为客观的结局指标。
安进公司。
