PHILADELPHIA — Patients with gout who underwent an intensive treat-to-target regimen of monthly up-titration of urate-lowering therapy (ULT) to reach a target serum urate level were significantly more likely to reach that goal at 1 year than were patients who received conventional gout management in a randomized, controlled trial.
Dr Sarah Black
These results came from the TICOG (Tight Control of Gout) trial, one of a handful of recent trials to test a treat-to-target strategy with ULT in the management of gout. Beyond the primary outcome of reaching target serum urate level of <5 mg/dL (<300 μmol/L), the results also showed that the tight-control strategy significantly lowered urate to a greater extent than conventional management, reduced tophus size in the first metatarsophalangeal (MTP) joint, and improved gray scale synovitis on ultrasound significantly more than with conventional management, Sarah Black, MBBS, a rheumatology trainee at Musgrave Park Hospital, Belfast, Northern Ireland, reported at the American College of Rheumatology (ACR) 2022 Annual Meeting.
“Based on these outcomes, we question whether gout is best managed in primary or secondary care. We think there is an argument for establishing specialist gout clinics with more time to focus on patient education to help improve outcomes. These clinics could be led by allied healthcare professionals, such as specialist nurses and pharmacists,” Black said at the meeting.
Gout management guidelines issued by the British Society for Rheumatology in 2017 call for a target serum urate level of <5 mg/dL, whereas the ACR’s 2020 guideline for the management of gout endorses a treat-to-target management strategy that aims for a serum urate level of <6 mg/dL.
The single-center, nonblinded trial recruited 110 patients aged 18–85 over a 3-year period to take ULT with allopurinol as first-line therapy starting at 100 mg/d. Everyone received the same advice regarding ULT up-titration, lifestyle changes, and gout education at baseline. The second-line agent for ULT was febuxostat (Uloric) 80 mg daily, with uricosuric drugs as third-line agents. All patients received colchicine or NSAID prophylaxis for gout flares for the first 6 months, depending on their comorbidities.
The trial excluded patients who had been treated with ULT within the past 6 months or had experienced prior hypersensitivity to ULT, severe renal impairment (creatinine clearance <30 mL/min as measured by estimated glomerular filtration rate), significant liver impairment, or any other significant medical disease affecting life expectancy shorter than 1 year.
Conventional management consisted of urate level review at 0, 6, and 12 months with up-titration at each visit and primary care management of ULT between reviews until the target serum urate level was reached. In the tight-control group, monthly up-titrations occurred at the Musgrave Park Hospital at visits with the study team that were led by a rheumatologist and a specialist pharmacist.
A total of 48 patients in the conventional arm and 47 in the tight-control arm completed the trial. At baseline, monosodium urate crystals were detected in joint aspirates in 56% of patients receiving tight control and in 58.5% of those receiving conventional management. The mean serum urate level was 490 μmol/L (8.24 mg/dL) for tight-control patients and 470 μmol/L (7.9 mg/dL) for conventionally managed patients.
By 1 year, 89.4% of patients in the tight-control group had achieved the target urate level, compared with 39.6% in the conventional-management group (P < .001). At 6 months, serum urate had declined by 37.6% with tight control, vs 18% with conventional management. By the end of the trial, the median allopurinol dose was 400 mg with tight control (range, 200 – 900 mg) and 200 mg with conventional management (range, 0 – 400 mg). A total of 89% of patients were taking allopurinol at the end of the trial.
As expected, tight control led to more flares per month on average (0.35 vs 0.13) in the 79 patients for whom complete data on flare frequency were available.
On blinded ultrasound evaluations, the median diameter of the first MTP tophus declined significantly more with tight control than with conventional management (-4.65 mm vs -0.30 mm; P = .003). Gray-scale synovitis in the knee improved in 63% of patients undergoing tight control, compared with 14% of conventionally managed patients (P = .043). The researchers observed no difference in resolution of the double contour sign or in the number of erosions between the groups, although the 1-year time frame may not have been long enough to see resolution and improvement, Black said.
Black said that a follow-up study is planned with the same patient cohort at 3 years.
When asked about the feasibility of monthly ULT titration visits for gout management, audience member Tuhina Neogi, MD, professor of epidemiology at Boston University and chief of rheumatology at Boston Medical Center, told Medscape Medical News, “We don’t have a lot of data to guide us in that regard, and I also think it depends on what the increment of the dose titration is, but we generally do recognize that therapeutic inertia is bad — keeping someone on a dose for a long time. For me, I don’t think monthly is unreasonable if you have good prophylaxis [against acute flares].”
Neogi also noted that such monthly assessments don’t have to take place at a hospital. “I think there are many different practice models in which it could be implemented [that are not physician-driven].”
The study had no outside funding. Black has disclosed no relevant financial relationships. Neogi has received consulting fees from a variety of pharmaceutical companies, including Alnylam, Regeneron, Eli Lilly, EMD Serono, Novartis, Pfizer, and GlaxoSmithKline.
American College of Rheumatology (ACR) 2022 Annual Meeting: Abstract 1579. Presented November 13, 2022.
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