One- and 2-year Flare Rates After Treat-to-Target and Tight-Control Therapy of Gout

Results From the NOR-Gout Study

Till Uhlig; Lars F. Karoliussen; Joe Sexton; Tore K. Kvien; Espen A. Haavardsholm; Fernando Perez-Ruiz; Hilde Berner Hammer


Arthritis Res Ther. 2022;24(88) 

In This Article


Patient Characteristics

Of 211 patients, 186 completed follow-up at year 1 (88.2%)[19] and 173 patients (82.0%) at year 2. No statistical differences were observed between baseline characteristics in 2-year completers versus non-completers.

SUA decreased from mean 500 μmol/L at baseline to 311 μmol at 1 year and 324 μmol/L at year 2, and 85.5% of patients were at target < 360 μmol at year 1 and 78.6% at year 2. Demographics and baseline characteristics are shown in Table 1 for all patients, and for those with and without flares during months 9–12 in years 1 and during year 2. Patients were predominantly middle-aged men with a mean disease duration of around 8 years, and 16.6% had subcutaneous tophi.

All patients initiated or escalated ULT. Only 14.7% (31/211) of patients had ever used ULT with allopurinol and none had used febuxostat, while 78% had experience ever with NSAID, and about half with each colchicine and prednisolone. During the first year, prescription of allopurinol decreased from 95.0% to 87.6% due to switch to febuxostat and increased for febuxostat from 3.5 to 12.4%. Mean doses for allopurinol remained just below 300 mg and below 60 mg for febuxostat. Flare prophylaxis with colchicine was used by 76.3% (161/211) of patients from baseline, with 72.3% (146/202) using colchicine at 1 month, 75.6% (146/193) at 2 months, 42.8% (80/189) at 3 months, and 14.5% (27/187) at 6 months follow-up. NSAIDs and prednisolone were not used as prophylaxis for flares.


In the first year, 80.6% (150/186) of patients experienced at least one gout flare and 26.0% (45/173) during the second year. The cumulative incidence of flares during the study is shown in Figure 1. The mean number of flares was 2.7 (SD 2.8) during the first year and 0.7 (SD 2.19) during year 2 (median 2 and 0, respectively). Flares before study entry had been experienced by 92.3% of patients and more than five flares by 49% (Table 1), and 73.4% of patients had experienced at least one other flare in the last year before inclusion.

Figure 1.

Cumulative incidence of flares during year 1 and after 2 years (n = 186)

Table 2 gives incidence numbers of flare per month, aggregated for 3-month periods and cumulatively during the first year in patients with at least one flare. The flare frequency in year 1 was highest during months 3–6 (46.8%) and was in the following 3-month periods between 30.1% and 37.6% (Figure 2).

Figure 2.

Flare frequency during the 3 months periods in year 1 and in year 2 after treat-to-target ULT

Characteristics for SUA, drug use, and flare history are displayed in Table 3 for patients with flares in the 3-month periods of year 1 and during year 2. Patients with and without flares were over time not consistently statistically different for demographic and disease-related factors.

The distribution of flares during year 1 among patients is presented as a cumulative probability plot in Figure 3, demonstrating the median number of flares to be two, and 10% of patients had six or more flares.

Figure 3.

Cumulative probability plot for number of flares during the first 12 months of treat-to-target ULT (n = 186). Every patient is represented by one dot, sorted from low to high

Prediction of Flares

Measures for baseline urate deposition (clinical tophi, ultrasound and DECT measures) were all bivariately related to flares in year 1 (months 9–12), but baseline ultrasound and DECT sum scores were the only variables which were associated with flares in year 2. There was no consistent relationship between other variables and flares at year 2, including SUA levels or allopurinol dose. For months 9–12, some other baseline factors were significantly associated with flares in bivariate analyses: more co-morbidities, more frequently experience with NSAID and colchicine ever, more flares before study entry, higher pain during the worst flare ever, worse physical function (SF-36 physical component summary), and lower self-efficacy (Table 1).

In multivariable logistic regression analyses with adjustment for age, gender, and disease duration, only baseline ultrasound and DECT sum scores were consistent predictors of flares, both during months 9–12 and year 2 (Table 4). Tophaceous disease was an independent predictor for flares during months 9–12, in addition to self-efficacy of pain and previous experience with colchicine, but none of these predicted flares during year 2.

Neither baseline SUA nor final ULT dose with allopurinol after 1 and 2 years were associated with incidence of a new flare during months 9–12 or year 2. Further, no other demographic or life-style characteristics predicted gout flares.

In sensitivity analyses, we examined the relationship between previous ULT and flares and stratified also for patients who still used prophylaxis after 3 and 6 months. No relationship for previous ULT and flares was observed. There was a higher frequency of flares during months 9–12 in patients using prophylaxis at months 3 versus not (49.4% vs. 25.3%, p < 0.001), but not for flares in year 2. Prophylaxis status at month 6 was not related to flares during months 9–12 or year 2.