Lifestyle modification and urate-lowering therapy not only led to declines in serum urate levels in patients with gout, but also successfully decreased the volume and burden of monosodium urate (MSU) crystals in these patients, a German study confirmed.
In a cohort of 83 patients who received either a lifestyle intervention or treatment with allopurinol or febuxostat (Uloric), serum urate levels fell from a mean of 7.2 mg/dL at baseline to 5.8 mg/dL at follow-up, which averaged 18 months later, according to Jürgen Rech, MD, of Friedrich-Alexander University Erlangen-Nurnberg, and colleagues.
And over that same time period, MSU crystal volume fell from 0.33 cm3 to 0.20 cm3, the researchers reported online in .
The gold standard of gout diagnosis is the identification of MSU crystals in synovial fluid, but in many cases, the crystal deposits are in the soft tissue surrounding the joints, which presents difficulties in aspiration.
Accordingly, dual-energy computed tomography (DECT) has been increasingly used to detect and quantify these crystal deposits, and scoring systems have been developed. However, few studies have addressed the question of whether therapeutic interventions actually affect crystal volume and burden over time.
So Rech's group conducted a prospective study of patients with symptomatic gout who had MSU deposits visible on DECT of both feet and ankles at baseline. The scoring system used to quantify the crystal volume included the first metatarsophalangeal joint, the toes, the midfoot/ankle, and soft tissue, with scores ranging from 0 to 12.
All patients were given lifestyle advice based on international recommendations, including alcohol avoidance and limitations of fructose-containing beverages and meat/shellfish intake. Participants also were advised to limit purine ingestion to 200 mg/day.
Patients who had recurrent gout attacks were initiated on medical therapy. The first-line treatment was allopurinol, started in dosages of 100 mg/day and titrated up to a maximum of 600 mg/day to meet a serum urate target below 6 mg/dL. Those who were unable to tolerate allopurinol were given febuxostat beginning at 80 mg/day and titrated to 120 mg/day to reach the urate target.
Of the 83 patients included, more than 80% were men, whose mean age was 59 and whose mean disease duration was 2.5 years. A total of 24 were given the lifestyle intervention alone, 29 received allopurinol at a mean dosage of 316 mg/day, and 22 received febuxostat at a mean dosage of 87 mg/day. An additional two patients received benzbromarone, and six withdrew from the study.
While all patients who remained in the study showed improvements in serum urate levels and MSU volume, those who were given urate-lowering therapy had a greater magnitude of benefit. For instance, the serum urate levels declined from 7.2 to 6.7 mg/dL in the lifestyle group but from 7 to 5.5 mg/dL in the allopurinol group and from 7.8 to 5.1 mg/dL in the febuxostat group. In addition, urate scores decreased from 2.8 to 1.5 in the lifestyle group, from 3.6 to 1.7 in the allopurinol group, and from 6.4 to 4.3 in the febuxostat group.
"Absolute change in the extent of MSU deposits was higher in the febuxostat group than with allopurinol, which itself was higher than lifestyle intervention. In contrast, patients who stopped treatment did not show any decline in MSU deposits," the researchers wrote.
They also found that 58.3% of patients in the lifestyle group had no detectable deposits at follow-up, as did 41.4% and 27.3% of the allopurinol and febuxostat patients, respectively. The baseline crystal burden was the only factor associated with reaching a deposit-free state; levels and changes in serum urate and demographic factors had no association.
The most frequent area of crystal deposition was the soft tissue, being detected in 85.5% of patients. Additional involvement of the toes was seen in 51.8%, the metatarsophalangeal joint in 47%, and the midfoot/ankle in 37.3%. The largest depositions were in the soft tissue, particularly in the area around the Achilles tendon.
Complete resolution was observed in 36.1% of crystals located in the soft tissue, in 30.1% located in the toes, 27.7% in the metatarsophalangeal joint, and 13.3% in the midfoot/ankle.
Assessing the effects of treatment on crystal deposition is of critical importance, "since MSU deposits but not serum urate levels are the central pathology in gout. Mere lowering of serum urate level without any impact on MSU deposits would reflect 'lab cosmetics' rather than disease modification," the researchers stated.
"Xanthine oxidase inhibitor treatment and, to a lesser extent, lifestyle intervention significantly reduced the burden of MSU deposits, suggesting that lowering serum urate levels is accompanied by partial regression of the tissue lesions in gout," the team concluded.
Further longitudinal evaluation will be required to determine whether complete resolution of crystals occurs with extended urate-lowering therapy, Rech and co-authors noted.
Disclosures
The authors reported no financial conflicts.
Primary Source
Arthritis & Rheumatology
Ellmann H, et al "Effects of conventional uric acid lowering therapy on monosodium urate crystal deposits" Arthritis Rheum 2019; doi:10.1002/art.41063.