Titre
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.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Dalbeth, N.
Auteure/Auteur
Botson, J.
Auteure/Auteur
Saag, K.
Auteure/Auteur
Kumar, A.
Auteure/Auteur
Padnick-Silver, L.
Auteure/Auteur
LaMoreaux, B.
Auteure/Auteur
Becce, F.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1778-7254
Statut éditorial
Publié
Date de publication
2024-07
Volume
91
Numéro
4
Première page
105715
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Randomized Controlled Trial
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
Patients received pegloticase (8mg every 2weeks)+MTX (15mg/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> )<0.5cm <sup>3</sup> were excluded to minimize artifact contributions. V <sub>MSU</sub> and bone-erosion remodeling were assessed.
Eight patients (6 MTX, 2 PBO) were included. Included patients had received 52weeks (5 MTX), 42weeks (1 PBO), and 6weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU<6mg/dL on allopurinol (n=2)/febuxostat (n=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.
Rapid V <sub>MSU</sub> depletion during pegloticase therapy was observed with concomitant bone remodeling within 1year. Following pegloticase discontinuation, V <sub>MSU</sub> reduction slowed or stopped even when SU was maintained<6mg/dL with oral ULT.
NCT03994731.
Patients received pegloticase (8mg every 2weeks)+MTX (15mg/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> )<0.5cm <sup>3</sup> were excluded to minimize artifact contributions. V <sub>MSU</sub> and bone-erosion remodeling were assessed.
Eight patients (6 MTX, 2 PBO) were included. Included patients had received 52weeks (5 MTX), 42weeks (1 PBO), and 6weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU<6mg/dL on allopurinol (n=2)/febuxostat (n=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.
Rapid V <sub>MSU</sub> depletion during pegloticase therapy was observed with concomitant bone remodeling within 1year. Following pegloticase discontinuation, V <sub>MSU</sub> reduction slowed or stopped even when SU was maintained<6mg/dL with oral ULT.
NCT03994731.
Sujets
PID Serval
serval:BIB_8B75A90F4F5A
PMID
Open Access
Oui
Date de création
2024-03-08T14:57:50.839Z
Date de création dans IRIS
2025-05-21T00:41:11Z
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Nom
38447697.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
2.4 MB
Format
Adobe PDF
PID Serval
serval:BIB_8B75A90F4F5A.P001
URN
urn:nbn:ch:serval-BIB_8B75A90F4F5A2
Somme de contrôle
(MD5):c63ce153b0c8751a6cf3cb2ecda9c3b6