Denosumab did not improve computerized tomography erosion scores when added to intensive urate-lowering therapy in gout: Results from a pilot randomized controlled trial.
Journal
Seminars in arthritis and rheumatism
ISSN: 1532-866X
Titre abrégé: Semin Arthritis Rheum
Pays: United States
ID NLM: 1306053
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
12
06
2021
revised:
11
10
2021
accepted:
13
10
2021
pubmed:
28
10
2021
medline:
19
3
2022
entrez:
27
10
2021
Statut:
ppublish
Résumé
Disordered osteoclast activity has been implicated in the pathogenesis of gouty bone erosion. We sought to determine if the addition of denosumab (a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand - RANKL) to intensive urate-lowering therapy (ULT) improves gouty bone erosion. Open-label, parallel-group pilot randomized controlled trial in which 20 participants with gout with at least one confirmed conventional radiographic foot bone erosion were assigned in a 1:1 allocation to receive denosumab (60 mg subcutaneous every 6 months) added to intensive ULT (serum urate ≤5 mg/dL or 300 µmol/L at the time of randomization and continued for the duration of the study), or intensive ULT alone. The primary outcome was the change in the bilateral foot and ankle computed tomography (CT) bone erosion score from baseline to 12 months, assessed by an experienced musculoskeletal radiologist blinded to study assignment. Secondary outcomes included change in serum C-terminal telopeptide (CTX), and patient reported outcomes of pain and function. Although serum CTX declined markedly in the denosumab/ULT group compared with the ULT alone group, there was no interval change in CT erosion score in either the denosumab/ULT or ULT alone group after one year of follow-up. Other secondary outcomes did not differ between groups. There were two severe adverse events: One patient developed atrial fibrillation (on denosumab/ULT) and another atrial flutter (on ULT alone). In this pilot study, denosumab did not offer additional benefit to intensive urate lowering therapy for gouty bone erosion.
Sections du résumé
BACKGROUND/PURPOSE
Disordered osteoclast activity has been implicated in the pathogenesis of gouty bone erosion. We sought to determine if the addition of denosumab (a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand - RANKL) to intensive urate-lowering therapy (ULT) improves gouty bone erosion.
METHODS
Open-label, parallel-group pilot randomized controlled trial in which 20 participants with gout with at least one confirmed conventional radiographic foot bone erosion were assigned in a 1:1 allocation to receive denosumab (60 mg subcutaneous every 6 months) added to intensive ULT (serum urate ≤5 mg/dL or 300 µmol/L at the time of randomization and continued for the duration of the study), or intensive ULT alone. The primary outcome was the change in the bilateral foot and ankle computed tomography (CT) bone erosion score from baseline to 12 months, assessed by an experienced musculoskeletal radiologist blinded to study assignment. Secondary outcomes included change in serum C-terminal telopeptide (CTX), and patient reported outcomes of pain and function.
RESULTS
Although serum CTX declined markedly in the denosumab/ULT group compared with the ULT alone group, there was no interval change in CT erosion score in either the denosumab/ULT or ULT alone group after one year of follow-up. Other secondary outcomes did not differ between groups. There were two severe adverse events: One patient developed atrial fibrillation (on denosumab/ULT) and another atrial flutter (on ULT alone).
CONCLUSIONS
In this pilot study, denosumab did not offer additional benefit to intensive urate lowering therapy for gouty bone erosion.
Identifiants
pubmed: 34706311
pii: S0049-0172(21)00190-6
doi: 10.1016/j.semarthrit.2021.10.002
pii:
doi:
Substances chimiques
Gout Suppressants
0
Uric Acid
268B43MJ25
Denosumab
4EQZ6YO2HI
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1218-1223Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Consultant for Arthrosi, Atom Bioscience, Horizon, Inflazome, LG Pharma, Mallinkrodt, SOBI, Takeda; research grants from Horizon, SOBI, and Shanton (KGS). Nicola Dalbeth reports consulting fees from AstraZeneca, Dyve, Selecta, Horizon, Arthrosi, and Cello Health, and speaker fees from Abbvie and Janssen. No other authors report conflicts of interests.