Background/Purpose: Bone erosion is a frequent complication of severe gout.  Computed tomography (CT) is considered the gold standard for measurement of bone erosion. CT studies have demonstrated a close relationship between monosodium urate (MSU) crystals and bone erosion, suggesting that dissolution of MSU crystals with urate-lowering therapy may influence the progression of bone erosion in gout.  The aim of this study was to examine whether serum urate lowering can prevent progression of bone erosion detected by CT in people with gout.

Methods: We conducted an imaging sub-study of a two-year randomized clinical trial of intensive vs. conventional allopurinol dosing in people with gout on allopurinol with serum urate (SU) ≥6mg/dL.  The intensive treatment group had immediate escalation of allopurinol dose to achieve SU <6mg/dL.  The control group had no change in their allopurinol dose in Year 1, and then had allopurinol dose escalation to achieve SU <6mg/dL.  Participants at one of the two study sites were invited into an imaging sub-study, which included CT scans of both feet, and plain radiographs (XR) of the hands and feet at the baseline, Year 1 and Year 2 visits.  CT scans were scored by two radiologists using a validated CT bone erosion scoring system for gout (erosion at seven bones/foot according to the RAMRIS method).  XR were scored for erosion and joint space narrowing by a radiologist and rheumatologist using a gout-modified Sharp van der Heijde score.  All scorers were blinded to treatment allocation, serum urate, and each other’s scores.  The pre-specified primary endpoint was change from baseline in CT erosion score, measured at Years 1 and 2.  Data were log_e transformed and analyzed using ANCOVA with baseline score as a covariate.

Results: Data were available for 88 participants (46 control, 42 dose escalation) at Year 1 and 82 (44 control, 38 dose escalation) at Year 2.  No difference between groups was observed for CT bone erosion scores from baseline to Year 1 (P=0.16).  However, differences between randomization groups were observed from baseline to Year 2 (P=0.015).  Over the two year study period, the rate of progression in CT erosion score was higher in the control group compared with the dose escalation group (percentage change (SEM) 7.5 (1.7) for the control group and 1.4 (1.8) for the dose escalation group) (Figure).  No differences between groups were observed in XR erosion scores or joint space narrowing scores over the observation period.  

Conclusion: This is the first randomized controlled trial to demonstrate that progression of bone erosion can be prevented using a treat to serum urate target strategy.  These findings support the concept that reduction of serum urate to sub-saturation levels can influence structural damage in gout. 

Figure. Change in CT erosion scores according to randomization group. Data are shown as percentage change in CT erosion scores (SEM).