Long-term urate-lowering therapy can affect structural damage and crystal deposition in patients with gout, according to research published in Arthritis and Rheumatology.
Using data from a previous study, researchers conducted a prespecified imaging study of patient data to examine if allopurinol dose escalation to achieve serum urate target influenced either bone erosion or monosodium urate crystal deposition in patients with gout.
At the start of the current study, paired imaging data were available for 87 participants (45 control, 42 dose escalation). Imaging included dual-energy computed tomography (DECT) scans of feet and plain radiographs of hands and feet at baseline, year 1, and year 2.
The prespecified primary endpoint of the study was the change from baseline in computed tomography (CT) bone erosion score as measured at years 1 and 2. Secondary endpoints included the change from baseline in monosodium urate crystal burden, assessed via DECT; change from baseline in radiograph erosion score; and change from baseline in radiographic joint space narrowing score.
Study participants were primarily men (91% in the control and 93% in the dose escalation groups) >60 years old. Mean disease duration was 21 ± 12 years in the control and 17 ± 13 years in the dose escalation groups. Participants in the dose escalation group had higher doses of allopurinol and lower serum urate concentrations at year 1 compared with the control group; both groups were similar at year 2.
Over time, researchers noted an increase in CT erosion scores. By year 2, progression was higher among individuals in the control group compared with individuals in the dose escalation group (+7.8% and +1.4%, respectively). Plain radiograph erosion and joint space narrowing scores did not differ between the two groups.
Researchers noted substantial reductions in DECT urate volume over time, and over the study period, DECT reduction volume was similar in both groups (−20.5% for the control and −28.3% for the dose escalation groups). An analysis separating patients according to achievement of serum urate target found that persons who achieved serum urate target at year 2 had “significantly greater DECT urate volume reduction over the study period.”
Additional analyses found that DECT urate volume correlated with joint damage measures — a higher correlation was found between DECT urate volume and CT erosion and radiograph erosion scores (r = 0.58-0.65 and r =0.54-0.57, respectively; P <.001 for both) compared with radiograph-measured joint space narrowing (r = 0.25-0.38; P <.02).
The primary limitation of the study was incomplete participation in the imaging study; however, the researchers noted that the clinical features of individuals who did participate were “broadly similar” to individuals who declined to participate.
“This is the first randomized controlled trial to demonstrate that progression of bone erosion can slow and potentially be prevented using a treat to serum urate target strategy,” the researchers concluded.
Disclosures: Dr Dalbeth reported receipt of research grant funding from Amgen Inc. and AstraZeneca Pharmaceuticals LP; speaker fees from AbbVie Inc.; Horizon Pharma; Janssen Pharmaceuticals, Inc.; and Pfizer Inc.; and consulting fees from AstraZeneca Pharmaceuticals LP, Dyve Biosciences; Hengrui Therapeutics, Inc.; Horizon Pharma; and Kowa Company Ltd. Dr Stamp reported receipt of consulting fees from AstraZeneca Pharmaceuticals LP.
Dalbeth N, Billington K, Doyle A, et al. Effects of allopurinol dose escalation on bone erosion and urate volume in gout: a dual energy CT imaging study of a randomized controlled trial [published online May 13, 2019]. Arthritis Rheumatol. doi:10.1002/art.40929