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Background/Aims Research has shown nurse-led gout clinics provide better outcomes compared to usual care. This District General Hospital set up a pilot nurse-led gout clinic in autumn 2019. This aimed to improve patients' understanding of their condition, achieve better control of serum uric acid levels (SUA), reduce flares and prevent Emergency Department attendances. Methods A modified clinic protocol, closely modelled on BSR guidance was agreed within the department. With consultant supervision, one nurse specialist provided a mix of in-person and telephone appointments. Targets were set aiming for SUA <360mumol/L for most patients and <300mumol/L for those with erosive change or tophi. All patients were offered prophylaxis. Patients required a rheumatologist's diagnosis of gout or crystal confirmation for enrolment. Exclusion criteria were significant renal or hepatic derangement. Within 3 months of the service starting SARS-CoV-2 impacted the operation of healthcare worldwide and led to the closure of routine outpatient clinics in Northern Ireland. A decision was made to switch the gout clinic to run entirely by telephone. Blood testing was facilitated through primary care and phlebotomy hubs. Results Over a 19-month period, 78 patients were treated and audited through this clinic: 69 men and 9 women. Average age was 57, mean SUA 509 mumol/L at referral and 322 mumol/L on discharge. 69 patients received allopurinol and 9 received febuxostat. No patients required uricosuric drugs. All patients were offered and agreed to take prophylaxis with a majority (85.8%) remaining on it for 3-6 months. Patients required a mean of 3.38 appointments prior to discharge from the clinic. The mean dose of urate lowering therapy on discharge was 315.9mg allopurinol and 93.3mg febuxostat. 95% experienced >=2 flares during their enrolment in the clinic with no patients requiring Emergency Department attendance due to gout flare. Conclusion The nurse-led gout clinic was well received by patients and was effective as a telephone service during the pandemic when so many services were stood down. The clinic was able to continue to provide education, deliver effective reductions in uric acid as well as reduce incidence of flares and Emergency Department attendances. Lower doses of urate lowering therapy than expected were needed to achieve target. A small number of patients were discharged prior to enrolment for initial non-engagement which may have been exacerbated by the lack of face-to-face appointments. Our COVID-19 model did struggle with those patients needing an interpreter. In-person initial appointments have since been restarted;however, a greater proportion of reviews will continue to be offered by telephone given the unexpected success of the model. This audit showed that a nurse-led gout clinic can run successfully, even during a pandemic with a significant reliance on telephone consultations.
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Background: Under the current situation of COVID-19 pandemic, more medical resources are assigned to the prevention and control of the pandemic, while relatively less attention is paid to patients with chronic diseases. Previous studies reported that COVID-19 deaths were mainly observed among male patients with multiple comorbidities, and the major comorbidities were hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic bronchitis, all of which are chronic diseases. As one of the most common chronic diseases that occurs in male, no report regarding how COVID-19 impacts gout patients psychologically due to the general susceptibility, their mental state and willingness to adhere to ULT treatment and the actual ULT adherence so far. This study aims to assess urate-lowering therapy adherence and the relationship with medication beliefs, self-efficacy, depression, anxiety, and COVID-19 pandemic-related concern in Chinese gout patients during the COVID-19 outbreak. Method(s): The cross-sectional study employed a total of 101 gout patients receiving urate-lowering therapy to evaluate adherence, medication beliefs, self-efficacy, depression, anxiety, and COVID-19 pandemic-related concern via a mobile app-based questionnaire. Statistical analysis was performed using SPSS 22.0. Result(s): 101 valid responses were included in the statistical analysis. Patients' adherence rate to urate-lowering therapy during the COVID-19 outbreak was 22.8%, higher than that in normal periods (9.6%). Compared with adherent groups, non-adherent gout patients had shorter disease duration, lower self-efficacy, lower Necessity about urate-lowering therapy score, higher Concerns about urate-lowering therapy score, and smaller Necessity-Concerns differential. Depression and anxiety rates (3.0% and 5.0%, respectively) during the COVID-19 break were lower than that in normal periods. Additionally, depression, anxiety, as well as COVID-19 pandemic-related concern (27.7%) were not related to ULT adherence. Conclusion(s): Adherence rate to urate-lowering therapy in Chinese gout patients during the COVID-19 outbreak was 13.2%, higher than normal times, but still very poor. Except for a little concern about being more susceptible to the virus, patients' mental state is relatively good. While the country puts great efforts in COVID-19 prevention and control, attention must also be paid to the medication management of patients with chronic diseases such as gout.
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Objective: The aim was to test the feasibility of a randomized controlled trial exploring whether omega-3 fatty acid supplementation limits gout flares during treat-to-target urate-lowering treatment (T2T-ULT). Methods: Adults with at least one gout flare in the past 12 months and serum urate (SU) ≥360 µmol/l were recruited from general practices (primary method) and randomly assigned 1:1 to receive omega-3 fatty acid supplementation (4 g/day) or placebo for 28 weeks. At week 5, participants began T2T-ULT. The primary outcome was drop-out rate. Secondary outcomes were recruitment rate, outcome data completeness, the number, severity and duration of gout flares between weeks 5 and 28, and study drug compliance. Results: Ninety-five per cent of randomized participants (n = 60) completed all study visits. The primary method recruitment rate was 2.2%. Fifty and 42 participants achieved SU < 360 and 300 µmol/l (6 and 5 mg/dl), respectively. The number of gout flares [median (interquartile range): active 1 (0-2) and placebo 1 (0-2)], flare duration [mean (s.d.): active 7.00 (4.52) days and placebo 7.06 (8.14) days] and time to first flare [hazard ratio (95% CI) 0.97 (0.50, 1.86)] were comparable between both arms. Study drug compliance was high and comparable in both arms [median (interquartile range) returned capsule count: active 57 (26-100) and placebo 58 (27-154)]; red blood cell omega-3 fatty acid index increased twofold in the active arm and remained unchanged in the control arm. Conclusion: The study demonstrated feasibility and provided useful metrics for conducting a community-based gout flare prophylaxis trial. Study registration: ISRCTN; https://www.isrctn.com/; ISRCTN79392964.
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Purpose: Gout in kidney transplant (KT) recipients can be severe and particularly challenging to manage. Pegloticase co-therapy with immunomodulators improved urate lowering therapy (ULT) response rates over phase 3 monotherapy trials by reducing anti-drug antibodies.1,2 This open-label trial (PROTECT NCT04087720) examined pegloticase safety and efficacy in KT patients with uncontrolled gout. Method(s): KT recipients with uncontrolled gout (serum urate [SU]>=7 mg/dL, intolerance/ inefficacy to ULT and >=1 of the following: tophi, chronic gouty arthritis, >=2 flares in past year) and functioning KT graft (eGFR>=15 ml/min/l.73m2) on stable immunosuppressive (IS) therapy (KT>l year earlier) received pegloticase (8 mg every 2 weeks for 24 weeks). SU response during Month 6 (SU <6 mg/dL for >=80% of time) and Health Assessment Questionnaire (HAQ) pain (most severe: 100) and Disability Index (HAQ-DI, max: 3) scores were evaluated. Patients discontinuing treatment before Month 6 were considered nonresponders. Patients discontinuing due to COVID-19 concerns were excluded from analysis if no data points were available in Month 6. Result(s): 20 patients enrolled (mean+/-SD;age: 53.9+/-10.9 years, 85% male, time since KT: 14.7+/-6.9 years, SU: 9.4+/-1.5 mg/dL, gout duration: 7.9+/-11.6 years;all on >=2 IS) and 14/20 completed treatment. 16/18 (88.9% [95% CI: 65.3, 98.6]) were SU responders vs 43.5% previously reported3 without immunomodulation. Substantial SU reductions during treatments were reported in 18/20 patients completing or discontinuing for non-SU monitoring rule reasons (pre-dose SU>6 mg/dL at 2 consecutive visits). No notable eGFR changes were observed up to 3 months follow-up. In patients completing treatment, HAQ-pain and HAQ-DI mean scores improved by 35.5+/-31.5 and 0.3+/-0.6, respectively, at Week 24 (n=13 and n=14). 7 serious adverse events, deemed unrelated to pegloticase, were reported in 5 patients. No anaphylaxis or infusion reaction events occurred. Conclusion(s): Pegloticase was safe and effective in treated KT patients with uncontrolled gout, achieving a higher durable response rate than in previously-reported patients not on IS therapy along with improved HAQ scores indicative of quality of life impact. These findings are consistent with other reports of immunomodulation with pegloticase.
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BACKGROUND: Patients with impaired kidney function were found at a high risk of COVID-19 hospitalization and mortality in many observational, cross-sectional, and hospital-based studies, but evidence from large-scale prospective cohorts has been lacking. We aimed to examine the association of kidney function-related biomarkers and their genetic predisposition with the risk of developing severe COVID-19 in population-based data. METHODS: We analyzed data from UK Biobank to examine the prospective association of abnormal kidney function biomarkers with severe COVID-19, defined by laboratory-confirmed COVID-19 hospitalizations. Using genotype data, we constructed polygenic risk scores (PRS) to represent an individual's overall genetic risk for these biomarkers. We also identified tipping points where the risk of severe COVID-19 began to increase significantly for each biomarker. RESULTS: Of the 502,506 adults, 1650 (0.32%) were identified as severe COVID-19, before August 12, 2020. High levels of cystatin C (OR: 1.3; 95% CI: 1.2-1.5; FDR = 1.5 × 10-5 ), serum creatinine (OR: 1.7; 95% CI: 1.3-2.1; p = 3.5 × 10-4 ; FDR = 3.5 × 10-4 ), microalbuminuria (OR: 1.4; 95% CI: 1.2-1.6; FDR = 4 × 10-4 ), and UACR (urinary albumin creatinine ratio; OR: 1.4; 95% CI: 1.2-1.6; p = 3.5 × 10-4 ; FDR = 3.5 × 10-4 ) were found significantly associated with severe COVID-19. Individuals with top 10% of PRS for elevated cystatin C, urate, and microalbuminuria had 28% to 43% higher risks of severe COVID-19 than individuals with bottom 30% PRS (p < 0.05). Tipping-point analyses further supported that severe COVID-19 could occur even when the values of cystatin C, urate (male), and microalbuminuria were within their normal value ranges (OR >1.1, p < 0.05). CONCLUSIONS: Findings from this study might point to new directions for clinicians and policymakers in optimizing risk-stratification among patients based on polygenic risk estimation and tipping points of kidney function markers. Our results call for further investigation to develop a better strategy to prevent severe COVID-19 outcomes among patients with genetic predisposition to impaired kidney function. These findings could provide a new tool for clinicians and policymakers in the future especially if we need to live with COVID-19 for a long time.
Subject(s)
COVID-19 , Renal Insufficiency , Adult , Humans , Male , Cystatin C/urine , COVID-19/genetics , Genetic Predisposition to Disease , Cross-Sectional Studies , Uric Acid , Albuminuria/genetics , Biomarkers , KidneyABSTRACT
Background: Data on the course and outcomes of the coronavirus disease 2019 (COVID-19) in patients with gout are scarce, as gout is underrepresented in leading COVID-19 and rheumatological Scientific publications [1]. Objectives: To describe clinical changes, quality of life, therapy of gout before and after COVID-19, and the clinical course of severe acute respiratory syndrome-related coronavirus 2 (SARS-Cov-2) infection in the cohort of patients with gout. Methods: In total, 84 males with gout were examined before the pandemic, during COVID-19 (March 2020 to December 2021) and 6 months after SARS-Cov-2 infection. The severity of COVID-19 in our cohort was determined. We conducted a comparative analysis of clinical and laboratory data, Gout Activity Score (GAS), urate-lowering (UST) and symptomatic therapy, Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Short Form 36 (SF-36) Health Survey Questionnaire. Statistical difference of qualitative indicators was carried out using the Pearson Chi-square test (χ2), quantitative indicators using the Student's or the Wilcoxon test between groups. Results: The mean age (mean±SD) of the study patients was 51.07±7.45 years and the disease duration was 9.84±6.02 years. Most SARS-CoV-2 infected patients with gout exhibited a moderate illness (40.48%), almost every third (28.57%) had mild, 21.43% had severe and 9.52% had critical illness. Comparison of pre-COVID-19 vs 6-month post-COVID-19 data demonstrated an increase of gout fares in preceding 6 months (0.7±0.59 vs 4.35±2.25, p<0.001), serum uric acid level (5.9±1.54 vs 7.62±1.99, p<0.01), GAS (3.83±0.4 vs 6.1±1.63, p<0.01), non-steroidal anti-infammatory drug intake (19.05% vs 72.62%, p<0.001), colchicine (27.38% vs 53.6%, p<0.001), and corticosteroid use (5.95% vs 34.52%, p<0.001), but decreased intake of ULT (88.09% vs 77.38%, p>0.05), SF-36 PCS (43.7 ± 6.19 vs 36.08±6.54, p<0.01) and SF-36 MCS (48.35±5.89 vs 40.13±6.84, p<0.01). Conclusion: The current study identifed the majority of patients with gout had a moderate course, every ffth had a severe course and 9.52% had a critical course of COVID-19. In the post-COVID-19 period, we found a six-fold increase in gout fares, rising gout activity by 59.3%, more frequent medication use for symptomatic therapy of gout, decreased physical and mental health in the cohort of patients with gout.
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Background: Coronavirus disease causes a proximal tubule dysfunction of kidneys, inducing uric acid loss [1]. It has been established that several changes in laboratory markers (C-reactive protein (CRP), ferritin, interleukin-6 (IL-6)) can predict the severity of Covid-19 [2]. The purpose of this retrospective study was to analyze whether uric acid could act as another predictor of severe Covid-19. Objectives: To evaluate the relationship between the severity of Covid-19 and uric acid levels on admission to the hospital. Methods: This retrospective study included 150 hospitalized patients with con-frmed Covid-19 (mean age 60.3±14.6 years;52% were men), the severity of which was determined by the presence and type of oxygen support: (1) without O2, (2) O2 by mask or nasal cannula, (3) continuous positive airway pressure, (4) positive bi-pressure in the airways or high-fow oxygen, (5) invasive ventilation. Among them, 90 subjects required oxygen support, and 60 people didn't. The mortality rate in our study was 9.3%. The average uric acid level was compared with patients without Covid-19 (40 subjects). The study included patients who didn't receive urate-lowering therapy. Levels of CRP, ferritin, IL-6, D-dimer were also determined on admission. The Spearman's rank coefficient was used for measuring correlation. Results: The mean uric acid level in patients with coronavirus disease was 251.5±104.1 μ mol/L;without Covid-19 it was signifcantly higher - 328.6±96.9 μ mol/L (p<0.001). Approximately one in four (24.6%) Covid-19 patients had uric acid levels below the lower limit of normal (208 μ mol/L for men, 155 μ mol/L for women). A decrease in serum uric acid levels was also observed in patients suffering from asymptomatic hyperuricemia or gout. However, there was no correlation between uric acid levels and disease severity (r=0.01, p=0.88). Also, uric acid levels did not correlate with other laboratory markers of severe Covid-19 (CRP: r=0.07, p=0.73;ferritin: r=0.15, p=0,07;IL-6: r=0.11, p=0,22;D-dimer: r=0.02, p=0,79). Conclusion: Low uric acid levels are common in patients with Covid-19, but are not predictive of a more severe course of this disease. A correlation between uric acid and the level of other laboratory markers of severe Covid-19 was not found.
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Background: When uncontrolled gout cannot be managed with oral urate-lower-ing therapies, pegloticase is one of the few remaining treatment options. Patients receiving infusion therapies experienced treatment interruptions due to the COVID-19 pandemic. As with other biologic therapies, patients can develop antidrug antibodies (ADAs) against pegloticase, and longer infusion intervals can result in higher rates of pegloticase immunogenicity.1 The literature suggests that co-administering an immunomodulator with pegloticase can markedly decrease the proportion of patients who develop ADAs,2 increasing the proportion with sustained urate-lowering response.3 Objectives: This case series reports one rheumatologists' experience with a gap in pegloticase therapy during the COVID-19 pandemic. Methods: Uncontrolled gout patients who underwent pegloticase treatment during 2019/2020 and had a gap in therapy of ≥28 days were identifed. Patient, clinical, and treatment (number post-gap infusions, immunomodulation co-therapy) characteristics were retrospectively examined, along with urate-lowering response following therapy interruption. Patients who had a serum urate (SU) <6 mg/dL after the last post-gap pegloticase infusion were considered to have recaptured response. Results: 7 patients (5 men, 64.3±13.5 years, pretherapy sUA: 7.76±2.47 mg/dL, 6 had tophi) were included with 2 remaining on therapy at data collection. Eleven gaps were noted with an average gap duration of 11.4±9.3 weeks (median: 9 weeks). For the last gap in therapy, patients received 13.9±7.0 infusions (range: 4-22) before the gap and 7.0±4.1 infusions (range: 2-14) after (Figure 1). Four patients (57%;Patients 1, 2, 5, 7) had recaptured urate-lowering at last pegloticase infusion, all of whom began immunomodulation (3 methotrexate, 1 mycophenolate mofetil/hydroxychloroquine) prior to resuming pegloticase. Of the 3 patients without response recapture, 2 initiated MTX after resuming pegloticase. 4 patients (57%) experienced ≥1 AE, including mild infusion reaction (n=1), acute gout flare (n=2), clinically meaningful decrease in eGFR (14.8 ml/min/1.73m2, n=1), heart attack (n=1), and anemia (n=1). Conclusion: These cases suggest that it may be possible to recapture urate-low-ering response to pegloticase in some patients, particularly in the presence of immunomodulation. These preliminary fndings are important to this vulnerable patient population, particularly during the COVID-19 pandemic. Further study is needed to confrm our fndings.
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PURPOSE: To report a case of ribavirin-associated severe hyperuricemia in an immunocompromised patient treated for respiratory syncytial virus (RSV) infection. SUMMARY: A 21-year-old male with a past medical history of B-cell acute lymphoblastic leukemia was in full remission after allogenic bone marrow transplantation complicated with chronic graft-versus-host disease. He was hospitalized due to fever, malaise, and respiratory symptoms. A diagnosis of RSV upper respiratory tract infection complicated by secondary pneumonia was made, and oral ribavirin (600 mg in 3 divided doses daily) and intravenous levofloxacin (750 mg once daily) were initiated. On day 2 of the hospital admission, the patient's uric acid levels had increased from a baseline of 4 to 6 mg/dL to 19.3 and 22.2 mg/dL after the fourth and fifth doses of ribavirin, respectively, and his serum creatinine steadily had increased from a baseline of 0.7 to 0.8 mg/dL to 1.6 mg/dL. Ribavirin was discontinued after the sixth dose, and a single dose of intravenous rasburicase (7.5 mg) was administered. On day 3, the patient's serum uric and creatinine concentrations had decreased to 4.7 mg/dL and 1.1 mg/dL, respectively. He continued to recover on antibiotics and was discharged with normal uric acid and serum creatinine levels. CONCLUSION: We report a case of severe hyperuricemia and acute kidney injury that developed early after initiation of ribavirin for RSV infection and suspected bacterial pneumonia in an immunocompromised patient without hepatitis C, requiring ribavirin discontinuation and rasburicase administration. To our knowledge, this is the first reported case of severe hyperuricemia in a patient treated with ribavirin for RSV infection rather than chronic hepatitis C. Clinicians should be aware of the possibility of acute and severe hyperuricemia following ribavirin administration.