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


Study Design and Participants

NOR-Gout (Gout in Norway) is a prospective, observational single-center study in a hospital-based rheumatology unit. Patients were eligible if having a gout attack within the last month, had increased SUA (> 360 μmol/L), and no contraindication for ULT. Other severe co-morbidities including chronic kidney disease stage 3b and higher were exclusion criteria. Patients were consecutively included according to the protocol (ACTRN12618001372279). In all patients, a diagnosis of gout was based on identification of monosodium urate crystals in polarized microscopy after arthrocentesis[19] performed by a rheumatologist. The study had been approved by the regional ethics committee, included patient representatives in project planning, and was performed in accordance with the declaration of Helsinki. All patients provided written informed consent. The sponsor of the study was Diakonhjemmet Hospital.


Patients received at baseline individual information by trained research nurses on gout, including non-pharmacological and pharmacological management. Drug use was recorded for NSAID, colchicine, prednisolone, and for ULT (allopurinol, febuxostat) at every visit which also included registration of drug dosage and adverse events. All patients not already on ULT started as recommended[13,20] with oral allopurinol 100 mg once per day and escalated by 100 mg increments monthly according to SUA concentrations until a maximum of 900 mg daily. If there is intolerance for allopurinol, febuxostat was started at 40 mg once daily and escalated monthly to 80 and 120 mg as needed. Probenecid or lesinurad could be added if necessary but were not used in any patients. Patients received flare prophylaxis, with prescribed colchicine 0.5–1 mg daily, individualized for 3–6 months, as recommended for the first months in current EULAR recommendations in 2015 when the study was initiated.[20] In this treat-to-target approach, ULT was escalated to reach a serum urate target level of < 360 μmol/L (or < 300 μmol/L if clinical tophi were present), and the dose was maintained when the target was reached.


A study nurse and a rheumatologist (HBH, LK) (who also performed ultrasound) assessed patients at baseline as well as after 3, 6, 12, and 24 months. Additional scheduled visits with only the study nurse were at 1, 2, and 9 months, and if necessary monthly, until the treatment target was reached. Telephone contact with review of the SUA result could substitute for face-to-face visits. During the second year, patients were followed by their general practitioners as needed.

Flare Definition

A gout flare during months 9–12 in year 1 was the primary clinical outcome. At every clinical visit during the 2-year study, the patient self-reported gout flares since the last visit during a structured interview with the study nurse who recorded the flares. If in doubt, the patient and study nurse discussed whether an experienced episode with pain or swelling was to be defined as a gout flare or not.

At baseline, self-reported information on number of flares ever and during the last year before study entry was collected by questionnaire as well as pain severity during the most recent and the strongest attack (0–10 numerical rating scales), with 0 = no pain and 10 = unbearable pain. Flares were reported as the frequency of patients having had ≥ 1 flare as well as the total number of flares, at all study time points, as recommended.[21] The number of self-reported flares with joint swelling in the previous year and also in total before the study was categorized into 0, 1, and 2–5.


Demographics and Self-reported Measures. At baseline, patients reported age, gender, ethnicity, marital status, family history of for gout, disease duration, highest level of education, comorbidities, and working status. For comorbidities, the Self-Administered Comorbidity Questionnaire (SCQ) was used (range 0–36);[22] it includes 12 medical problems, allocating 1 point per problem including presence, receiving treatment, and causing a functional limitation.

Daily and previous smoking, consumption of alcohol and sugar sweetened drinks, and the frequency of physical activity were reported by patients.

Questionnaires. Questionnaires at each visit recorded present joint pain due to gout, general pain, fatigue, and patient global assessment of disease activity, all on 0–10 numerical rating scales.

Physical function was measured with the Health Assessment Questionnaire (HAQ) without adjustment for help or devices.[23] Health status was assessed by the Short Form general health questionnaire (SF-36).[24]

Self-efficacy with subscales for pain (5 items) and symptoms (6 items) was measured with the Arthritis Self-Efficacy Scales.[25] This instrument measures whether patients have confidence in coping with pain, function, and other symptoms due to arthritis (numeric rating scales 10–100, 100 = highest).

The Beliefs about Medicines Questionnaire (BMQ)[26] explores patients' beliefs about medicines and includes scales on perceived necessity or concerns for the patient's own medicines (5 items each, range 5–25) and for perceived general overuse and harm of medicines (4 items each with range 4–16). Items were scored on Likert scale 1–5, 5 = highest agreement, and a high scale score reflects stronger belief in the expressed concept.

Clinical Assessments. Clinical assessments included weight and height for calculation of body mass index (BMI) and 44-swollen and tender joint counts and clinical examination for subcutaneous tophi.

Imaging With Ultrasound and Dual-energy Computed Tomography (DECT). To assess the level of crystal deposition, all patients were examined by ultrasound and DECT. Ultrasound was at baseline scored as previously described[27] (score 0–3 of double contour, tophi and aggregates) with calculation of total ultrasound sum scores.

DECT baseline scoring of feet and ankles applied the semiquantitative Bayat method (scores 0–3),[28,29] and a sum score for the four regions (first metatarsophalangeal joint, other joints of the toes, ankles and midfeet, and tendons) was derived.

Laboratory Assessments. SUA was analyzed at each study visit and is presented both as a dichotomous (cutoff 360 μmol/L) and continuous variable, as recommended.[21] Laboratory examinations included SUA (μmol/L), erythrocyte sedimentation rate (ESR) mm/h, C-reactive protein (CRP) mg/L, creatinine (μmol/L), and eGFR (ml/min/1.73m2, CKD-EPI formula) at baseline and follow-up visits.


Descriptive measures of baseline variables are presented using frequency, mean, and standard deviation. Differences between groups with and without flares during defined time periods were explored using independent sample T-test and by the χ 2 test or Fisher's exact, as appropriate. A cumulative probability plot shows flares in the first year, where every patient is one observation, and flares are ordered from 0 to maximum flare number.

Odds ratio (OR) with 95% confidence intervals (95% CI) were calculated by logistic regression analyses after performing bivariate analyses with baseline candidate predictor variables of flares at 9–12 months and during the second year. These variables were selected from baseline data, based on their potential clinical relevance, and were in case of possible statistical relevance (p < 0.10) then entered in stepwise backwards multivariable logistic regression analyses, adjusting for age and gender and disease duration and retained if statistically significant (p < 0.05). Analyses were performed with IBM SPSS statistics (version 27).