Rapidly separating dissolving microneedles with sustained-release colchicine and stabilized uricase for simplified long-term gout management

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.

The effect of initiation of urate-lowering treatment during a gout flare on the current episode: a meta-analysis of randomized controlled trials

Abstract Objective: The objective was to evaluate whether initiation of urate-lowering treatment (ULT) during an acute gout flare prolonged the current episode. Methods: A comprehensive search of MEDLINE and Web of Science databases was conducted from their inception to 15 March 2021. Five randomized controlled trials (RCTs) with 381 patients met the inclusion criteria. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were used for estimating the clinical efficacy of ULT in acute gout. Results: There was no statistical difference in days to resolution (intent-to-treat analysis) (SMD, 0.68; 95% CI — 0.42 to 1.78; I2, 49%; p = 0.22), the pain visual analogue score (VAS) by day 10 (SMD, — 0.07; 95% CI — 0.30 to 0.16; I2, 0%; p = 0.53), C-reactive protein (CRP) from day 7 to 10 (SMD, — 1.14; 95% CI — 5.63 to 3.36; I2, 55%; p = 0.62), erythrocyte sedimentation rate (ESR) from day 7 to 10 (SMD, — 2.51; 95% CI — 5.46 to 0.45; I2, 0%; p = 0.10) and the recurrence of gout flares within 28-30 days (OR 0.78; 95% CI 0.29 to 2.09; I2, 0%; p = 0.62). Conclusion: Initiation of ULT during an acute gout flare did not prolong the duration of the flare. However, larger sample size studies are needed to confirm this finding. Trial registration number PROSPERO (CRD42021234581).

A single-centre experience of febuxostat as a second-line urate-lowering therapy

@#Introduction: The purpose of this study was to describe the local experience in terms of drug efficacy and safety using a new xanthine oxidase inhibitor, febuxostat, as a second-line urate lowering therapy (ULT) in gout patients with normal renal function and chronic kidney disease. Methods: This cross-sectional study included all gout patients who attended the rheumatology clinic from January 2013 to June 2018 and had received febuxostat as a second-line ULT. Analysis focused on the proportion of gout patients who achieved target serum urate (sUA) of <360 μmol/L, duration taken to achieve target sUA, and febuxostat dosage at achievement of target sUA. Safety assessments included comparison of serum creatinine, estimated glomerular filtration rate (eGFR), and serum alanine aminotransferase (ALT) at baseline, at achievement of target sUA, and at 12-monthly intervals. Results: Majority (90.9%) of patients achieved target sUA. Median duration required to achieve target sUA was 5.5 months with IQR (interquartile range) of 8.5. Five (22.7%) patients achieved target sUA within one month of therapy with febuxostat 40 mg per day. Eleven (55%) patients achieved target sUA within six months and 16 (80%) by 12 months. Equal proportion of patients achieved target sUA with febuxostat 40 mg per day and 80 mg per day, respectively. There was no significant difference in the changes in serum creatinine level, eGFR and ALT from baseline and at achievement of target sUA, nor at 12-monthly intervals throughout the duration of febuxostat therapy. Apart from three patients who developed hypersensitivity reactions to febuxostat, no other adverse events were reported. Conclusion: A significant proportion of gout patients with CKD managed to achieve target sUA with a lower dose of febuxostat at 40 mg per day and it is reasonable to maintain this dose for up to six months before considering dose escalation.

Effects of urate-lowering therapy on inflammatory responses, gout flares occurances, and the achieved target rate of serum uric acid in acute gout / 中华内分泌代谢杂志

Objective To observe the effects of urate-lowering therapy ( ULT) on indexes of inflammation, the frequency of gout flares, compliance of ULT, and the achieved rates of serum uric acid in patients at acute stage. Methods 151 patients with acute gout flares were randomly divided into observation group ( 60 cases with ULT in the acute phase) and control group (91 cases with ULT after 2 weeks of complete remission from acute flares). Visual analogue pain scores (VAS), joint swelling scores, white blood cell counts, erythrocyte sedimentation rates (ESR), as well as high sensitive-C reactive protein (hs-CRP) were measured respectively and compared between two groups. The observation group was treated with 40 mg/d of febuxostat for 12 weeks after effectively achieved inflammation ( VAS<3 points) , while the control group was treated with the same therapy after 2 weeks of symptoms complete remission from acute gout flares. Finally, these indexes were followed and recorded, including the number of gout flares, the compliance of ULT, the changes of liver and kidney function, and the proportion of patients with serum uric acid<360μmol/L. Results There was no statistical difference in the baseline condition, VAS pain scores, joint swelling scores, white blood cell counts, ESR, and hs-CRP between two groups after different ULTs ( all P>0.05) . There was no statistical difference in the frequency of gout flares between two groups during the ULT of 12 weeks ( P=0.658) . At the end of 12 weeks, the serum uric acid in the observation group was significantly lower compared with the control group [(318.38±95.16 vs 398.12±120.13)μmol/L,P<0.01]. The compliance rate of ULT and the rate of reaching the standard of serum uric acid<360μmol/L in the observation group were higher than those in the control group ( both P<0.01) . Conclusion The treatment of ULT with patients after effective achieved of acute gout inflammation has no detrimental effects on VAS pain, joint swelling score, the conversion of inflammation index, and the number of gout flares, while improving the compliance of ULT and the achieved rate of serum uric acid.

Role of metabolic factors in formation of kidney stones and its non-surgical intervention / 中华全科医师杂志

The prevalence of kidney stone is increasing,and its recurrence risk is very high.This article reviews the current literature on causes of stone formation,its relation to metabolic factors,and dietary and medical intervention for kidney stones.It aims to emphasis the importance of comprehensive medical management based on the improvement of metabolic disorders,for treatment of kidney stone and reduction of its recurrence rate.

An Update on the Diagnosis and Management of Gout

Gout is characterised by monosodium urate crystal deposition in synovial fluid, articular surfaces, and other tissues, which occurs after the chronic elevation of uric acid levels above the saturation point of 360mmol/L (6mg/dL). Amongst all inflammatory arthropathies, gout is the most common. Given the rising prevalence of gout, it is imperative to keep up with the recent advances in the nunderstanding of the pathophysiology, diagnostic modalities, and therapies of gout. It is important to understand that gout is not as harmless a condition as perceived in the past and is, in fact, associated with significant morbidity and even mortality if left untreated. This article seeks to provide a useful review of the current standard of care and to discuss new developments in the management of gout applicable in any family medicine practice setting.