Months Of Urate-lowering Therapy Research Articles

Imaging Follow-Up of MSU Crystal Depletion

Imaging modalities such as ultrasonography (US) and dual-energy computed tomography (DECT) have been recognized for their abilities to detect monosodium urate (MSU) crystals. The main described features of gout detected by DECT (tophus) or US (tophus, double contour [DC] sign and aggregates) are very specific for the diagnosis of gout, but the impact of imaging on the follow-up of MSU deposits is not well known. US and DECT allow for visualization of the disappearance of MSU crystals under adequate urate-lowering therapy (ULT). An OMERACT US score and a DECT urate score have been described. The dissolution of the DC sign is detectable on US after 3 months, whereas a decreased size or volume in tophus can be observed on US or DECT after 6 months of ULT. Serum urate level decrease is associated with a reduction in MSU crystal deposition. Finally, the risk of gout flare is associated with the baseline MSU burden and with the degree of dissolution of crystal deposition. All these data confirm that imaging could be useful in managing gout, even if its exact place in routine practice remains unclear.

The use of febuxostat in comorbid patients with gout in real clinical practice: own data

Objective: to evaluate the efficacy and safety of febuxostat (Azuriks®) in the treatment of patients with gout and concomitant diseases.Patients and methods. An observational, open-label, single-centre study of the results of febuxostat use in 85 gout patients with insufficient prior allopurinol efficacy or its intolerance. The median age of patients was 56.2 [49; 59] years, among them 83.5% were men. All patients had comorbid diseases, mainly cardiovascular pathology (76.5%) and chronic kidney disease (60%). The achievement of target values of uric acid (UA) during 4 months of urate-lowering therapy and its safety were assessed.Results and discussion. After 4 months of therapy with febuxostat, 25% of patients reached the target values of UA. Exacerbations at an early stage of the use of urate-lowering therapy were rare and were characterized by a lesser severity of the articular syndrome. Normalization of purine metabolism was accompanied by a decrease in the laboratory activity index (CRP level) to values corresponding to the interictal period of gout. Febuxostat was well tolerated.Conclusion. According to the data obtained, in patients with gout and concomitant diseases, febuxostat allows reaching target UA values in a short time without dose titration, while a high safety profile is noted.

Quantitative assessment of crystal dissolution in gout during urate-lowering therapy with computer-aided MicroPure imaging: a cohort study

BackgroundTo evaluate whether MicroPure imaging, an ultrasound (US) image-processing technique with computer-aided analysis, can quantitatively detect crystal dissolution during urate-lowering therapy (ULT) in gout.MethodsThis was a prospective study of gout patients requiring ULT. The first metatarsophalangeal joints were examined using US and MicroPure before and after 3 months of ULT. Elementary lesions of gout, including the double contour sign (DCS), aggregates, tophi, erosion, and other US features were recorded at baseline and 3 months. MicroPure imaging features were automatically calculated by a self-developed software. Patients were divided into goal-achieved and goal-not-achieved groups according to their urate levels at 3 months. The US and MicroPure imaging features of the two groups were analyzed at baseline and 3 months.ResultsA total of 55 consecutive patients were enrolled (25: goal-achieved group; 30: goal-not-achieved group). US findings demonstrated that the power Doppler signal grade decreased at 3 months, regardless of the group (both P<0.05). From baseline to 3 months, tophi size and the DCS reduced in the goal-achieved group (both P<0.05), while the US aggregate features showed no difference (P=0.250). However, on the MicroPure imaging, the number and density of aggregates at 3 months decreased in the goal-achieved group (both P<0.05). There were no significant changes at 3 months in any of the MicroPure imaging features in the goal-not-achieved group (all P>0.05).ConclusionsIn comparison with B-mode US, computer-aided MicroPure imaging can sensitively and quantitatively detect aggregate dissolution during effective ULT after only 3 months of treatment.

Achievement of the target serum urate level among patients with gout treated with allopurinol or febuxostat in an arthritis clinic in the Philippines

Objective Gout is an important cause of disability among Filipinos, despite measures for effective management. This study aims to determine attainment of target serum uric acid level (SUA ≤ 6 mg/dl) among patients with gout given urate-lowering therapy (ULT) over 6–12 months. Methods This is a single-center, prospective cohort study conducted in one adult Arthritis Clinic at the University of the Philippines-Philippine General Hospital which included 138 patients with gout (1977 ACR criteria), SUA ≥ 6 mg/dl prior to ULT, initiated on ULT (allopurinol or febuxostat), with six months minimum follow-up and with SUA determination post-treatment. Results 37.7% (52/138) and 36.2% (50/138), achieved target SUA at 6 and 12 months. The factors associated with achieving target SUA in 6 months are BMI > 25 kg/m2 [OR 6.98, 95% confidence interval (CI) 1.44–33.88, p value = .016], allopurinol dose ≥ 300 mg (OR 15.76, 95% CI 2.24–111.06, p value = .006), and baseline SUA (OR 0.52, 95% CI 0.33–0.82, p value = .005). The factors associated with achieving target SUA in 12 months are employment (OR 5.51, 95% CI 1.00–30.33, p value = .050), baseline SUA (OR 0.45, 95% CI 0.28–0.74, p value = .002), and age at onset of gout (OR 1.08, 95% CI 1.01–1.15, p value = .026). Conclusion Target SUA level was not achieved at 6 and 12 months of ULT in most of this cohort. This mirrors the deficient control of gout and should urge health professionals to fully study and address the problem.

Predictive factors of tumour necrosis inhibitor treatment persistence for rheumatoid arthritis: An observational study in 8052 patients.

To determine whether changes in ultrasonography (US) features of monosodium urate crystal deposition is associated with the number of gouty flares after stopping gout flare prophylaxis. We performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting urate-lowering therapy (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (M6 to 12) and ULT was maintained. Outcomes were the proportion of relapsing patients between M6 and M12 according to changes of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse. We included 79 gouty patients (mean [±SD] age 61.8±14 years, 91% males, median disease duration 4 [IQR 1.5; 10] years). Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size≥50% at M6 was more frequent without than with relapse (54% vs. 26%, P=0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse. Probability of relapse was increased for patients with a decrease in tophus size <50% between M0 and M6 (OR 3.35 [95% confidence interval 0.98; 11.44]). A high reduction in US tophus size is associated with low probability of relapse after stopping gout prophylaxis. US follow-up may be useful for managing ULT and gout flare prophylaxis.

Limited Knee-Joint Range of Motion in Patients With Tophaceous Gout Improved With Medical Treatment: A 18-Months Follow Up.

Objectives: Tophi may occur within the knee joint causing limited knee-joint range of motion (knee motion). We investigated the relationships between knee motion, total intra-articular tophi size (tIA-tophi), and total subcutaneous tophi size (tSC-tophi) and determined knee motion improvement after continual urate-lowering therapy (ULT).Methods: A total of 26 patients with tophaceous gout and limited knee motion were enrolled. Inclusion criteria were age ≤ 60 years and preserved knee joint space on a plain radiograph. tSC-tophi were measured using a Vernier caliper and tIA-tophi were measured using magnetic resonance imaging software. All patients were re-evaluated after 12–24 months of continual ULT. Upon initial visit, knee motion was related to tIA-tophi and tSC-tophi.Results: After an average of 18.2 months of ULT, the reduction in tSC-tophi was correlated with the reduction in tIA-tophi (P = 0.014, r = 0.395) and improvement in knee motion (P = 0.038, r = 0.408). Knee motion can be eventually improved even in cases of poor initial knee motion (P = 0.000, r = –0.911) or large initial tIA-tophi (P = 0.014, r = 0.476). Tophi can occur in any location within the knee joint. In multiple lineal regression, knee motion was predicted to improve 8.39° for every 10cm of tIA-tophi reduction.Conclusions: Limited knee motion in patients with intra-articular tophi improved with medical treatment, regardless of initial severity. Furthermore, tSC-tophi can be used as an indicator of limited knee motion and their improvement as a predictor of knee motion improvement.

Better outcomes for patients with gout.

Gout is increasing in prevalence despite effective pharmacotherapies. Barriers to effective management are largely educational deficiencies. Sufferers, usually men, need to understand more about gout, especially that maintaining serum urate below 0.36mmol/L will eliminate recurrent attacks. Also, of great importance is appreciating that sub-optimal adherence to urate-lowering therapy (ULT) will result in a return of attacks. Prescribers also need to understand that acute attacks are likely to occur in the first few months of urate-lowering therapy (ULT), but these can be mitigated by commencing with a dose of ULT reflective of renal function and escalating the dose slowly, every 2-5weeks until target serum urate is achieved. Prophylaxis against acute attacks over the initial 6months period of ULT can be enhanced further with concomitant colchicine or nonsteroidal anti-inflammatory drugs (NSAIDs).Gout is largely managed in primary care. Rates of adherence to ULT are 50% or less, worse than most other chronic illnesses. Efforts at educating primary care physicians to, firstly, manage gout effectively and, secondly, to educate their gout patients sufficiently have not been successful. Allied health practitioners, such as nurses, working with prescribers in primary care settings and given the mandate to educate and manage patients with gout, have been spectacularly effective. However, this approach is resource intensive. 'Personalised' eHealth interventions show promise as an alternative strategy, notably in improving adherence to ULT.Numerous applications for smart phones (apps) are now available to assist people with chronic health conditions. Their design needs to accommodate the barriers and enablers perceived by patients to maintaining adherence to prescribed therapies. Personalised feedback of serum urate may represent an important enabler of adherence to ULT in the case of gout.Harnessing mobile apps to support patients managing their chronic illnesses represents an important opportunity to enhance health outcomes. Rigorous, patient-centred and driven development is critical. These tools also require careful evaluation for effectiveness.

New urate depositions on dual-energy computed tomography in gouty arthritis during urate-lowering therapy.

Reduction of urate depositions in the joints, on dual-energy computed tomography (DECT), in patients with gout during urate-lowering therapy (ULT) was demonstrated in previous studies. The aim of this study was to further investigate the changes in distribution of urate deposits during ULT. This randomized controlled trial enrolled 46 patients diagnosed with gout from Zhongshan Hospital, China, between October 2013 and June 2014. Epidemiological data, serum uric acid level, and arthritis attacks were recorded at monthly follow-up visits. DECT of bilateral feet and ankles was performed at baseline and after 6months of ULT. Overall, 163 areas of urate deposition were found in the 46 patients; of these, 133/163 (81.6%) areas were associated with former arthritis attacks. On DECT at 6months, the number of urate deposits decreased to 126, with 68 areas disappearing and 31 new deposits areas. The mean volume of urate deposits at baseline was 1.3±3.8cm3, decreasing to 0.6±2.1cm3 at the end of 6months (P=0.01), with 3/46 (6.5%) patients showing complete disappearance of urate deposits. New urate depositions were found in 21/46 (45.7%) patients, while urate depositions in some joints disappeared in some joints in 31/46 (67.4%) patients. High-sensitivity C-reactive protein was significantly lower in patients with new deposits (4.6±9.3 vs. 7.1±7.6mg/dL; P=0.01). There is dynamic redistribution of urate depositions in gout patients receiving ULT.

Current management of gout: practical messages from 2016 EULAR guidelines.

The European League Against Rheumatism published updated recommendations for the management of gout in 2016, comprising 3 overarching principles and 11 key recommendations for clinical practice. Patient education about the pathophysiology of gout and its comorbidities, as well as the existence of effective treatments are important, and understanding the principles of managing acute attacks and eliminating urate crystals by lifelong lowering of the serum urate (SU) below a target level are essential. Advice about lifestyle, diet, weight, and other risk factors, as well as the need to screen for, and manage, comorbidities is emphasized. For the treatment of flares, colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), and oral or intraarticular steroids, or a combination thereof, are recommended. In patients with frequent flares and contraindications to colchicine, NSAIDs, and corticosteroids, an interleukin-1 blocker should be considered. Urate-lowering therapy (ULT) should be discussed from the first presentation of the disease, and SU levels should be maintained at less than 6 mg/dl (360 µmol/l), or less than 5 mg/dl (300 µmol/l) in patients with severe gout. Allopurinol is recommended as first-line ULT with dose adjustment according to renal function. If the SU target cannot be achieved with allopurinol, then febuxostat, a uricosuric, or combining a xanthine oxidase inhibitor with a uricosuric should be considered. All ULTs should be started at low dose and titrated upwards until the SU target is achieved. Unless contraindicated, flare prophylaxis with low-dose colchicine or with NSAIDs at low dosage is recommended during the first 6 months of ULT. In patients with refractory gout, pegloticase can be considered.

Utility of the Morisky Medication Adherence Scale in gout: a prospective study.

BackgroundThe outcomes of any chronic illness often depend on patients’ adherence with their treatment. A tool is lacking to assess adherence in gout that is standardized, allows real-time feedback, and is easy to understand.ObjectiveWe set out to evaluate the utility of the 8-item Morisky Medication Adherence Scale (MMAS-8) in monitoring medication adherence in a multiethnic Asian gout cohort on urate-lowering therapy (ULT).MethodsThis cohort study recruited patients with gout where baseline and 6-monthly clinical data, self-report of adherence, and health status by Gout Impact Scale (GIS) and EuroQoL-5 dimension 3 levels were collected. Those who received at least 9 months of ULT were analyzed. Convergent and construct validities of MMAS-8 were evaluated against medication possession ratio (MPR) and known groups, clinical outcomes, and patient-reported outcomes. Internal consistency and test–retest reliability were assessed using Cronbach’s alpha and intraclass correlation coefficient (ICC), respectively.ResultsOf 91 patients, 92.3% were male, 72.5% Chinese with mean age 53.5 years. MMAS-8 (mean 6.17) and MPR (mean 96.3%) were poorly correlated (r=0.069, P=0.521). MMAS-8 did not differ between those who did or did not achieve target serum urate (SU) <360 µmol/L (P=0.852); or among those whose SU improved, stagnated, or worsened during follow-up (P=0.777). Adherence was associated with age (β=0.256, P=0.015) and education level (P=0.011) but not comorbidities, polypharmacy, or flare frequency. Concerns for medication side effects and anxiety or depression were associated with lower MMAS-8 (P<0.005). Internal consistency was acceptable (α=0.725) and test–retest reliability was satisfactory (ICC =0.70, 95% confidence interval [CI] 0.36–0.88).ConclusionMMAS-8 had limited construct validity in assessing medication adherence to ULT in our gout patients. Nevertheless, it identified patients bothered or worried about ULT side effects, and those with underlying anxiety or depression, for whom targeted education and coping support may be useful.

Ultrasound in gout: A useful tool for following urate-lowering therapy

ObjectiveWe aimed to determine the ability of ultrasonography (US) to show decrease or disappearance of urate deposits in gouty patients requiring urate-lowering therapy (ULT). MethodsTo be included in this prospective single-centre study, patients needed toexhibit (1) proven gout by monosodic urate (MSU) crystals in synovial fluid and (2) US-evidenced urate deposits (double contour [DC] sign and/or tophi) before starting ULT (allopurinol [n=4], febuxostat [n=12]). At baseline and after six months of ULT, one trained ultrasonographer assessed the knee and first metatarsophalangeal (MTP1s) joints. Serum uric-acid (SUA) level was assessed at baseline and at three and six months after ULT initiation. Correlation between US findings and achievement of SUA level objective (< 360μmol/L) was estimated by the kappa coefficient (κ). ResultsWe studied 16 patients (all males, mean age 61.0±18.3 years). The mean disease duration was 7.1±6.2 years. Tophi were found at clinical examination in 56% of patients. Baseline SUA levels were 688±153μmol/L. At baseline, US revealed tophi or a DC sign among 62.5 to 75% of patients in knees and 87.5% in MTP1s. After six months of ULT, none of the four patients, not achieving the SUA level objective, had disappearance of US features. Among the remaining 12 patients, US features (tophi or DC sign) disappeared or decreased in all but one with a stable DC sign in one MTP1. The correlation between the whole US examination and SUA level was excellent (κ=0.875). ConclusionsUS could show disappearance of urate deposits after ULT and appears to be well correlated with efficacy of ULT.

OP0008 Ultrasound in Gout: A Useful Tool for Follow-Up with Urate-Lowering Therapy

BackgroundRecently, ultrasonography (US) demonstratted its ability to detect urate deposition in gouty patients. Some US features have been suggested to be specific such as tophus and the double contour sign....