Background/Purpose: We recently demonstrated that synovitis is present in the vast majority of patients with inter-critical gout and that the severity of this synovitis did not correlate with serum urate levels¹.  The aim of this sub-study was to determine if aggressive serum urate lowering therapy can improve this chronic occult synovitis.

Methods: All patients in this sub-study had inter-critical gout and received a 3Tesla MRI with and without gadolinium of their index joint (i.e. the joint most often involved with acute attacks of gout) at their screening visit.  Each subject also had a serum urate level, CRP, and creatinine obtained on the same day.  If the subject had a serum urate level of ≥ 7.0mg/dL and evidence of synovial pannus (synovitis) on their MRI, they were eligible for enrollment.  All subjects were treated with febuxostat with a target serum urate level of ≤ 6.0mg/dL; each subject also received colchicine prophylaxis until month 6 (corticosteroids were not permitted).  At month 9, the MRI of the index joint was repeated and the severity/degree of synovial pannus (graded on a scale of 1-6 [1 best; 6 worst]) was compared to baseline. The MRI’s were read by two musculoskeletal radiologists in an independent and blinded fashion.  The primary endpoint was to determine if there was significant improvement in the severity of synovial pannus from baseline to month 9. 

Results: 25/32 subjects enrolled in this sub-study completed the entire protocol.  20 (80%) of the participants were males (17 Caucasian, 3 African-American, 2 Hispanic, 3 other) with an average age and disease duration of 57.2 years (range 40-70) and 10.1 years (range 1-31), respectively.  20/25 (80%) index joints were the first metatarsalphalangeal joint; the average number of attacks in the index joint was 8.3 (+/- 7.1 SD) with an average of 20.6 (+/- 27.1 SD) total attacks in any joint.  The average serum urate level and synovial pannus score at screening was 9.3 mg/dL (+/- 1.3 SD) and 3.66 (+/- 1.2 SD), respectively.  After 9 months of treatment with febuxostat, the average serum urate level decreased significantly to 5.36 mg/dL (+/- 1.4 SD; p<0.0001), but there was no significant change in the severity/degree of synovial pannus with the average score being 3.42 (+/- 1.3 SD; p=0.34).  The inter-reader agreement between the two radiologists for all of the MRIs was good (kappa=0.63).  There was also no significant change in the CRP or eGFR from screening to month 9.

Conclusion: Nine months of serum urate lowering therapy significantly decreases serum urate levels but has no effect on the chronic, occult, synovial-based inflammation of gout.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/an-assessment-of-the-response-of-chronic-occult-synovial-based-inflammation-of-gout-to-serum-urate-lowering-therapy/