Evaluating the safety and short-term equivalence of colchicine versus prednisone in older patients with acute calcium pyrophosphate crystal arthritis (COLCHICORT): an open-label, multicentre, randomised trial.

BACKGROUND: Acute calcium pyrophosphate crystal arthritis causes intense joint pain mainly affecting older people. Because guidance and evidence remain scarce, management of this disease relies on expert opinion. We therefore aimed to compare the safety and short-term equivalence of low-dose colchicine with oral prednisone in older patients with acute calcium pyrophosphate crystal arthritis. METHODS: We did an open-label, multicentre, randomised, trial (COLCHICORT) at six hospitals in Paris and northern France. We enrolled patients who were admitted to hospital who were 65 years or older and who presented with acute calcium pyrophosphate crystal arthritis with a symptom duration of less than 36 h. Diagnosis of calcium pyrophosphate crystal arthritis was made by the identification of calcium pyrophosphate crystals on synovial fluid analysis or typical clinical presentation (onset of joint pain and swelling). Key exclusion criteria included absence of calcium pyrophosphate crystals on synovial fluid analysis or a history of gout. Participants were randomly allocated (1:1), using a centralised electronic treatment group allocation module, to receive either colchicine 1·5 mg on day 1 and 1 mg on day 2 (ie, the colchicine group) or oral prednisone 30 mg on days 1 and 2 (ie, the prednisone group). The primary outcome was change in joint pain (measured by visual analogue scale [VAS] from 0 mm to 100 mm) at 24 h. Equivalence was determined whether the 95% CI of the between-group difference at 24 h was within the -13 mm to +13 mm margin in the per-protocol analysis. Adverse events were recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). This trial is completed and is registered with ClinicalTrials.gov, NCT03128905. FINDINGS: Between Feb 5, 2018, and May 7, 2022, 111 patients who were admitted to hospital were randomly assigned (57 [51%] to the colchicine group and 54 [49%] to the prednisone group). 95 (86%) of 111 patients were included in the per-protocol analysis (49 [52%] in the colchicine group and 46 [48%] in the prednisone group). The median age was 88·0 years (IQR 82·0-91·0) and 69 (73%) of 95 participants were women and 26 (27%) were men. Acute calcium pyrophosphate crystal arthritis affected mainly the knee in 46 (48%) of 95 participants, the wrist in 19 (20%), and the ankle in 12 (13%). Pain VAS at baseline was 68 mm (SD 17). At 24 h, change in pain VAS was -36 mm (SD 32) in the colchicine group and -38 mm (SD 23) in the prednisone group. The between-group difference in change in pain VAS at 24 h was -1 mm (95% CI -12 to 10), showing equivalence between the two drugs. In the colchicine group, 12 (22%) of 55 patients had diarrhoea, one (2%) had hypertension, and none had hyperglycaemia. In the prednisone group, three (6%) of 54 had diarrhoea, six (11%) had hypertension, and three (6%) had hyperglycaemia. No deaths occurred in the colchicine group; two deaths occurred in the prednisone group, which were deemed unrelated to prednisone (one due to infectious valvular endocarditis leading to heart failure, and one due to a stroke). INTERPRETATION: Colchicine and prednisone exhibit equivalent short-term efficacy for the treatment of acute calcium pyrophosphate crystal arthritis, with different safety profiles in the older population. FUNDING: French Inter-regional Hospital Program of Clinical Research.

Identification and characterization of peripheral vascular color-coded DECT lesions in gout and non-gout patients: The VASCURATE study.

OBJECTIVE: To characterize peripheral vascular plaques color-coded as monosodium urate (MSU) deposition by dual-energy computed tomography (DECT) and assess their association with the overall soft-tissue MSU crystal burden. METHODS: Patients with suspected crystal arthropathies were prospectively included in the CRYSTALILLE inception cohort to undergo baseline knees and ankles/feet DECT scans; treatment-naive gout patients initiating treat-to-target urate-lowering therapy (ULT) underwent repeated DECT scans with concomitant serum urate level measurements at 6 and 12 months. We determined the prevalence of DECT-based vascular MSU-coded plaques in knee arteries, and assessed their association with the overall DECT volumes of soft-tissue MSU crystal deposition and coexistence of arterial calcifications. DECT attenuation parameters of vascular MSU-coded plaques were compared with dense calcified plaques, control vessels, control soft tissues, and tophi. RESULTS: We investigated 126 gout patients and 26 controls; 17 ULT-naive gout patients were included in the follow-up study. The prevalence of DECT-based vascular MSU-coded plaques was comparable in gout patients (24.6%) and controls (23.1%; p=0.87). Vascular MSU-coded plaques were strongly associated with coexisting arterial calcifications (p<0.001), but not with soft-tissue MSU deposition. Characterization of vascular MSU-coded plaques revealed specific differences in DECT parameters compared with control vessels, control soft tissues, and tophi. During follow-up, vascular MSU-coded plaques remained stable despite effective ULT (p=0.64), which decreased both serum urate levels and soft-tissue MSU volumes (p<0.001). CONCLUSION: Our findings suggest that DECT-based MSU-coded plaques in peripheral arteries are strongly associated with calcifications and may not reflect genuine MSU crystal deposition. Such findings should therefore not be a primary target when managing gout patients.

Monosodium urate burden assessed with dual-energy computed tomography predicts the risk of flares in gout: a 12-month observational study : MSU burden and risk of gout flare.

BACKGROUND: Predicting the risk of flares in patients with gout is a challenge and the link between urate burden and the risk of gout flare is unclear. The objective of this study was to determine if the extent of monosodium urate (MSU) burden measured with dual-energy computed tomography (DECT) and ultrasonography (US) is predictive of the risk of gout flares. METHODS: This prospective observational study recruited patients with gout to undergo MSU burden assessment with DECT (volume of deposits) and US (double contour sign) scans of the knees and feet. Patients attended follow-up visits at 3, 6 and 12 months. Patients having presented with at least one flare at 6 months were compared to those who did not flare. Odds ratios (ORs) (95% confidence interval) for the risk of flare were calculated. RESULTS: Overall, 64/78 patients included attended at least one follow-up visit. In bivariate analysis, the number of joints with the double contour sign was not associated with the risk of flare (p = 0.67). Multivariate analysis retained a unique variable: DECT MSU volume of the feet. For each 1 cm3 increase in DECT MSU volume in foot deposits, the risk of flare increased 2.03-fold during the first 6 months after initial assessment (OR 2.03 (1.15-4.38)). The threshold volume best discriminating patients with and without flare was 0.81 cm3 (specificity 61%, sensitivity 77%). CONCLUSIONS: This is the first study showing that the extent of MSU burden measured with DECT but not US is predictive of the risk of flares.

The lack of association between the burden of monosodium urate crystals assessed with dual-energy computed tomography or ultrasonography with cardiovascular risk in the commonly high-risk gout patient.

BACKGROUND: Gout is associated with higher cardiovascular risk that increases with disease severity. The objective of this study was to explore the relationship between the extent of monosodium urate (MSU) crystal deposition, assessed with ultrasonography (US) and dual-energy computed tomography (DECT), and cardiovascular risk. METHODS: Gout patients were included in this cross-sectional study to undergo DECT scans for the assessment of total MSU volume deposition in the knees and feet, and US to evaluate the number of joints with the double contour (DC) sign. Participants were screened for traditional cardiovascular risk factors, and levels of the American College of Cardiology (ACC)/American Heart Association (AHA) 10-year risk for heart disease or stroke were calculated. The primary endpoint was the Spearman correlation coefficient ρ between DECT MSU volume and cardiovascular risk. RESULTS: A total of 42 patients were included; they were predominantly male (40/42) and aged 63.0 ± 13.2 years. Overall, 28/42 patients presented with the metabolic syndrome and the average 10-year coronary event or stroke risk according to the ACC/AHA (n = 33) was 21 ± 15%. Correlations between DECT volumes of MSU deposits in the knees, feet, and knees + feet and cardiovascular risk according to the ACC/AHA were very poor, with ρ = 0.18, -0.01, and 0.13, respectively. The was no correlation between the number of joints with the DC sign and cardiovascular risk (ρ = -0.07). DECT MSU deposit volume was similar in patients with and without metabolic syndrome (p = 0.29). CONCLUSIONS: The extent of MSU burden does not increase the estimated risk of cardiovascular events in gout patients.

Ultrasonography and dual-energy computed tomography provide different quantification of urate burden in gout: results from a cross-sectional study.

BACKGROUND: Ultrasonography (US) and dual-energy computed tomography (DECT) can assess urate burden in gout. The objective of this study was to compare the quantification of urate deposition provided by US to the one provided by DECT. METHODS: Patients with a diagnosis of gout were prospectively recruited to undergo quantification of urate deposition using US and DECT. US examination for tophi and the double contour (DC) sign was performed on the knees and feet and corresponding DECT scans provided volumes of tophi and of overall urate deposition. The primary endpoint was the intra-class correlation coefficient (ICC) of the volume of the index tophus measured by US and DECT and its 95% confidence interval (CI 95%). RESULTS: Of the 64 patients included, 34 presented with at least one tophus on US. DECT inter-reader agreement for urate deposition was perfect with an ICC of 1 (1-1) and good for the measurement of the index tophus with an ICC of 0.69 (0.47-0.83). The ICC for the measurement of the index tophus between the two techniques was poor with a value of 0.45 (0.1-0.71). The average ratio between the index tophi volume as assessed by DECT and US was 0.65. The number of DC-positive joints did not correlate with DECT volume of overall deposits (Spearman correlation coefficient of 0.23). CONCLUSIONS: DECT measurements of tophi give smaller volumes to the same tophi measured with US, and US signs of urate deposition in joints do not correlate with overall DECT volumes of extra-articular deposition.

Efficacy in current practice of switching between anti-tumour necrosis factor- α agents in spondyloarthropathies.

OBJECTIVE: Anti-TNF-α agents are remarkably effective in the treatment of SpAs. However, 30% of patients withdraw from anti-TNF-α agents yearly because of inadequate efficacy or side effects. The objective of this study was to assess in current practice the response to a second and a third anti-TNF-α. METHODS: Retrospectively, all records of patients who had received at least two anti-TNF-α agents have been studied. For axial forms, treatment was considered effective if 3 months after switching the patient had a favourable expert opinion or showed an improvement in BASDAI of at least 2 on a scale of 0-10 or an improvement of 50% (BASDAI 50). For peripheral forms, the treatment was considered effective if the patient had a favourable expert opinion or if a clinical improvement of >30% of the swollen and tender joint counts was established. The reasons for switching were: (i) primary non-responder; (ii) loss of efficacy; and (iii) occurrence of side effects. To identify response predictor factors bivariate analysis was performed. RESULTS: Three hundred and seventy-seven patients under anti-TNF-α agents were treated and 99 patients had received at least two anti-TNF-α agents. Twenty-eight of these 99 patients had been treated with three anti-TNF-α agents. Following the failure of a first anti-TNF-α, the response to a second agent was satisfactory in 80.8%. Patients who had received a third anti-TNF-α following failure of the first two also showed a satisfactory response in 82.1%. The reason for switching from the first or second agent was not predictive of the response. CONCLUSION: In the event of failure or intolerance to anti-TNF-α in the treatment of SpAs, performing a first or second switch produces a satisfactory therapeutic response.