Monosodium urate crystal depletion and bone erosion remodeling during pegloticase treatment in patients with uncontrolled gout: Exploratory dual-energy computed tomography findings from MIRROR RCT
Nicola Dalbeth , John Botson , Kenneth Saag , Ada Kumar , Lissa Padnick-Silver , Brian LaMoreaux , Fabio Becce
{"title":"Monosodium urate crystal depletion and bone erosion remodeling during pegloticase treatment in patients with uncontrolled gout: Exploratory dual-energy computed tomography findings from MIRROR RCT","authors":"Nicola Dalbeth , John Botson , Kenneth Saag , Ada Kumar , Lissa Padnick-Silver , Brian LaMoreaux , Fabio Becce","doi":"10.1016/j.jbspin.2024.105715","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>Monosodium-urate (MSU) crystal deposits can be visualized and quantified with dual-energy CT (DECT). Pegloticase lowers serum urate (SU) in uncontrolled gout patients, with methotrexate (MTX) co-therapy recommended to increase SU-lowering response rate and decrease infusion reaction risk. The literature on serial DECT-imaging during pegloticase<!--> <!-->+<!--> <!-->MTX co-therapy is sparse, with only 2 prior cases of rapid MSU deposition depletion with subsequent bone-erosion remodeling reported from a small open-label trial. Here, we report DECT findings during pegloticase treatment in a larger number of patients from a randomized controlled trial to confirm bone-erosion remodeling that follows MSU depletion with pegloticase. The influence of length-of-therapy is also explored.</p></div><div><h3>Methods</h3><p>Patients received pegloticase (8<!--> <!-->mg every 2<!--> <!-->weeks)<!--> <!-->+<!--> <!-->MTX (15<!--> <!-->mg/week orally) or pegloticase<!--> <!-->+<!--> <!-->placebo (PBO) during the MIRROR RCT trial. A subset underwent DECT-imaging on Day1 (first pegloticase infusion) and at Weeks 14, 24, and 52. Patients with paired baseline-Week 52 images were included. Imaged regions with baseline MSU-crystal volume (V<sub>MSU</sub>)<!--> <!--><<!--> <!-->0.5<!--> <!-->cm<sup>3</sup> were excluded to minimize artifact contributions. V<sub>MSU</sub> and bone-erosion remodeling were assessed.</p></div><div><h3>Results</h3><p>Eight patients (6 MTX, 2 PBO) were included. Included patients had received 52<!--> <!-->weeks (5 MTX), 42<!--> <!-->weeks (1 PBO), and 6<!--> <!-->weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU<!--> <!--><<!--> <!-->6<!--> <!-->mg/dL on allopurinol (<em>n</em> <!-->=<!--> <!-->2)/febuxostat (<em>n</em> <!-->=<!--> <!-->1). At Week 52, V<sub>MSU</sub> had markedly decreased in both the pegloticase<!--> <!-->+<!--> <!-->MTX and pegloticase<!--> <!-->+<!--> <!-->PBO treatment groups, with faster depletion during pegloticase therapy. Bone-erosion remodeling was observed in 29/42 (69%) evaluated erosions: 29 (69%) size decrease, 4 (9.5%) recortication, 3 (7.1%) new bone formation.</p></div><div><h3>Conclusion</h3><p>Rapid V<sub>MSU</sub> depletion during pegloticase therapy was observed with concomitant bone remodeling within 1<!--> <!-->year. Following pegloticase discontinuation, V<sub>MSU</sub> reduction slowed or stopped even when SU was maintained<!--> <!--><<!--> <!-->6<!--> <!-->mg/dL with oral ULT.</p></div><div><h3>Clinical trial registration</h3><p><span>NCT03994731</span><svg><path></path></svg>.</p></div>","PeriodicalId":54902,"journal":{"name":"Joint Bone Spine","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1297319X24000265/pdfft?md5=1568d89d2213619152abd17ef71d5735&pid=1-s2.0-S1297319X24000265-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Joint Bone Spine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1297319X24000265","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective
Monosodium-urate (MSU) crystal deposits can be visualized and quantified with dual-energy CT (DECT). Pegloticase lowers serum urate (SU) in uncontrolled gout patients, with methotrexate (MTX) co-therapy recommended to increase SU-lowering response rate and decrease infusion reaction risk. The literature on serial DECT-imaging during pegloticase + MTX co-therapy is sparse, with only 2 prior cases of rapid MSU deposition depletion with subsequent bone-erosion remodeling reported from a small open-label trial. Here, we report DECT findings during pegloticase treatment in a larger number of patients from a randomized controlled trial to confirm bone-erosion remodeling that follows MSU depletion with pegloticase. The influence of length-of-therapy is also explored.
Methods
Patients received pegloticase (8 mg every 2 weeks) + MTX (15 mg/week orally) or pegloticase + placebo (PBO) during the MIRROR RCT trial. A subset underwent DECT-imaging on Day1 (first pegloticase infusion) and at Weeks 14, 24, and 52. Patients with paired baseline-Week 52 images were included. Imaged regions with baseline MSU-crystal volume (VMSU) < 0.5 cm3 were excluded to minimize artifact contributions. VMSU and bone-erosion remodeling were assessed.
Results
Eight patients (6 MTX, 2 PBO) were included. Included patients had received 52 weeks (5 MTX), 42 weeks (1 PBO), and 6 weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU < 6 mg/dL on allopurinol (n = 2)/febuxostat (n = 1). At Week 52, VMSU had markedly decreased in both the pegloticase + MTX and pegloticase + PBO treatment groups, with faster depletion during pegloticase therapy. Bone-erosion remodeling was observed in 29/42 (69%) evaluated erosions: 29 (69%) size decrease, 4 (9.5%) recortication, 3 (7.1%) new bone formation.
Conclusion
Rapid VMSU depletion during pegloticase therapy was observed with concomitant bone remodeling within 1 year. Following pegloticase discontinuation, VMSU reduction slowed or stopped even when SU was maintained < 6 mg/dL with oral ULT.
期刊介绍：
Bimonthly e-only international journal, Joint Bone Spine publishes in English original research articles and all the latest advances that deal with disorders affecting the joints, bones, and spine and, more generally, the entire field of rheumatology.
All submitted manuscripts to the journal are subjected to rigorous peer review by international experts: under no circumstances does the journal guarantee publication before the editorial board makes its final decision. (Surgical techniques and work focusing specifically on orthopedic surgery are not within the scope of the journal.)Joint Bone Spine is indexed in the main international databases and is accessible worldwide through the ScienceDirect and ClinicalKey platforms.
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