Hmong microbiome ANd Gout, Obesity, Vitamin C (HMANGO-C): A phase II clinical study protocol.

BACKGROUND: Hmong men in Minnesota exhibit a high prevalence of gout and hyperuricemia. Although evidence of vitamin C's effectiveness as a treatment for gout is mixed, analysis of therapeutic benefit based on an individual's multiomic signature may identify predictive markers of treatment success. OBJECTIVES: The primary objective of the Hmong Microbiome ANd Gout, Obesity, Vitamin C (HMANGO-C) study was to assess the effectiveness of vitamin C on serum urate in Hmong adults with and without gout/hyperuricemia. The secondary objectives were to assess if 1) vitamin C impacts the taxonomic and functional patterns of microbiota; 2) taxonomic and functional patterns of microbiota impact vitamin C's urate-lowering effects; 3) genetic variations impact vitamin C's urate-lowering effects; 4) differential microbial biomarkers exist for patients with or without gout; and 5) there is an association between obesity, gut microbiota and gout/hyperuricemia. METHODS: This prospective open-labelled clinical trial was guided by community-based participatory research principles and conducted under research safety restrictions for SARS-CoV-2. We aimed to enroll a convenient sample of 180 Hmong adults (120 with gout/hyperuricemia and 60 without gout/hyperuricemia) who provided medical, demographic, dietary and anthropometric information. Participants took vitamin C 500mg twice daily for 8 weeks and provided pre-and post- samples of blood and urine for urate measurements as well as stool samples for gut microbiome. Salivary DNA was also collected for genetic markers relevant to uric acid disposition. EXPECTED RESULTS: We expected to quantify the impact of vitamin C on serum urate in Hmong adults with and without gout/hyperuricemia. The outcome will enhance our understanding of how gut microbiome and genomic variants impact the urate-lowering of vitamin C and associations between obesity, gut microbiota and gout/hyperuricemia. Ultimately, findings may improve our understanding of the causes and potential interventions that could be used to address health disparities in the prevalence and management of gout in this underserved population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04938024 (first posted: 06/24/2021).

Colchicine prophylaxis is associated with fewer gout flares after COVID-19 vaccination.

OBJECTIVES: COVID-19 vaccination often triggers a constellation of transitory inflammatory symptoms. Gout is associated with several comorbidities linked to poor outcomes in COVID-19, and gout flares can be triggered by some vaccinations. We analysed the risk of gout flares in the first 3 months after COVID-19 vaccination with inactivated virus, and whether colchicine can prevent gout flares following post-COVID-19 vaccination. METHODS: A clinical delivery population-based cross-sectional study was conducted in the Gout Clinic at the Affiliated Hospital of Qingdao University between February and October 2021. Study participants were selected using a systematic random sampling technique among follow-up patients with gout. We collected data, including vaccinations and potential risk factors, using a combination of interviews, health QR codes and medical records. Logistic regression was used to adjust for covariates. RESULTS: We enrolled 549 gout participants (median age 39 years, 84.2% vaccinated). For the 462 patients who received COVID-19 vaccine, 203 (43.9%) developed at least one gout flare in the 3 months after vaccination. Most of these flares were experienced within 1 month after the first (99/119 (83.2%)) or second (70/115 (60.9%)) dose of vaccine. Compared with unvaccinated participants, COVID-19 vaccination was associated with higher odds of gout flare within 3 months (adjusted OR 6.02; 95% CI 3.00 to 12.08). Colchicine use was associated with 47% less likelihood of postvaccine gout flare. CONCLUSION: COVID-19 vaccination was associated with increased odds of gout flare, which developed mainly in month 1 after each vaccine dose, and was negatively associated with colchicine prophylaxis.

Gout and the COVID-19 pandemic.

PURPOSE OF REVIEW: This review gives an overview of recently published articles on COVID-19 and gout. RECENT FINDINGS: People with gout are likely to be at an increased risk of poor outcomes after COVID-19 infection due to comorbid cardiometabolic conditions. The effects of chronic hyperuricemia on trained immunity, and the hyperinflammatory state induced by gout itself may also play a role. Frequent courses of glucocorticoids for gout flares may be associated with adverse outcomes after COVID-19 infection and reduced immunogenicity to the COVID-19 vaccination. Similarities between the pathophysiology of gout flares and the dysregulated inflammatory response of severe COVID-19 have been identified. Medications used in the treatment of gout, including colchicine and interleukin-1 inhibitors, have shown promise in the treatment of COVID-19 in clinical trials. Overall, the COVID-19 pandemic has had a negative impact on gout care, with patients reporting more difficulty with disease control, accessing medications and healthcare, and poorer quality of life. SUMMARY: The COVID-19 pandemic has created many challenges for people with gout. At present, there is a lack of guidance on the management of gout during the pandemic and paucity of research assessing outcomes of COVID-19 infection in people with gout.

Randomised controlled trial targeting habit formation to improve medication adherence to daily oral medications in patients with gout.

INTRODUCTION: Medication adherence for patients with chronic conditions such as gout, a debilitating form of arthritis that requires daily medication to prevent flares, is a costly problem. Existing interventions to improve medication adherence have only been moderately effective. Habit formation theory is a promising strategy to improve adherence. The cue-reward-repetition principle posits that habits are formed by repeatedly completing an activity after the same cue and having the action rewarded every time. Over time, cues become increasingly important whereas rewards become less salient because the action becomes automatic. Leveraging the cue-reward-repetition principle could improve adherence to daily gout medications. METHODS AND ANALYSIS: This three-arm parallel randomised controlled trial tests an adaptive intervention that leverages the repetition cue-reward principle. The trial will began recruitment in August 2021 in Boston, Massachusetts, USA. Eligible patients are adults with gout who have been prescribed a daily oral medication for gout and whose most recent uric acid is above 6 mg/dL. Participants will be randomised to one of three arms and given electronic pill bottles. In the two intervention arms, participants will select a daily activity to link to their medication-taking (cue) and a charity to which money will be donated every time they take their medication (reward). Participants in Arm 1 will receive reminder texts about their cue and their charity reward amount will be US$0.50 per day of medication taken. Arm 2 will be adaptive; participants will receive a US$0.25 per adherent-day and no reminder texts. If their adherence is <75% 6 weeks postrandomisation, their reward will increase to US$0.50 per adherent-day and they will receive reminder texts. The primary outcome is adherence to gout medications over 18 weeks. ETHICS AND DISSEMINATION: This trial has ethical approval in the USA. Results will be published in a publicly accessible peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04776161.

Gout during the SARS-CoV-2 pandemic: increased flares, urate levels and functional improvement.

INTRODUCTION: Gout is the most common inflammatory arthritis, but was not considered in most COVID-19 and rheumatic diseases reports. Our aim was to describe changes in clinical data, treatment, function and quality of life for gout patients during COVID-19 pandemic. METHODS: Prospective, descriptive and analytical study of 101 consecutive gout (ACR/EULAR 2015) patients from our clinic evaluated during pandemic by phone call (n=52) or phone call + face-to-face (n=68) that accepted to participate. Variables are demographics, clinical and treatment data, HAQ, EQ5D questionnaires and COVID-19-related data. Patients were divided in two groups: flare (n=36) or intercritical gout (n=65) also; available pre-pandemic data was obtained from 71 patients. Statistical analyses are X2, paired t-test and Wilcoxon test. RESULTS: Included gout patients were males (95.8%), mean (SD) age 54.7 (10.7) years and disease duration 16.4 (9.8) years; 90% received allopurinol, 50% colchicine as prophylaxis and 25% suspended ≥ 1 medication. Comparison of pre-pandemic vs pandemic data showed > flares (4.4% vs 36%, p=0.01), more flares in the last 6 months: 0.31 (0.75) vs 1.71 (3.1), (p=0.004 and > urate levels: 5.6 (1.7)vs 6.7 (2.2) mg/dL, p=0.016. Unexpectedly, function and quality-of-life scores improved: HAQ score 0.65 (2.16) vs 0.12 (0.17), p= 0.001. Seven patients were COVID-19-confirmed cases; they had significantly more flares, higher urate levels and lower allopurinol doses and two died. CONCLUSIONS: In gout patients, flares were 9 times more frequent during pandemic also, they had increased urate levels but led to an unexpected improvement in HAQ and functionality scores. Resilience and lifestyle changes in gout during COVID-19 pandemic require further studies. Key Points • COVID-19 pandemic is associated with 4 times more flares in gout patients. • Increased flares were also seen in previously well-controlled gout patients. • Increased serum urate levels were also found in gout patients during pandemic. • In our gout clinic, 8/101 patients were diagnosed as COVID-19+, and two of them died.

COVID-19 in patients with gout on colchicine.

Current data demonstrated that severe cases of coronavirus-disease-19 (COVID-19) require treatment with antiviral therapy, dexamethasone, supportive care, as well as some anti-rheumatic drugs, among them, cytokine inhibitors and colchicine. Colchicine is an anti-inflammatory drug that is being used in rheumatology for many years to treat mostly gout, calcium pyrophosphate deposition disease, and Familial Mediterranean Fever. Here, we present for the first time, two patients suffering from gout being treated with colchicine, who were affected from severe acute respiratory coronavirus-2 (SARS-CoV-2) syndrome. Both patients presented with mild symptoms of COVID-19 expressed with myalgias, arthralgias, and sore throat, while laboratory investigations showed only high acute phase reactants. Four weeks later, both patients were free of symptoms with negative SARS-CoV-2 tests and without any complications. To our knowledge, there are no other studies of gout arthritis and SARS-CoV-2 infection published so far. Thus, our preliminary conclusion is that chronic use of colchicine may mitigate the clinical picture and disease course of COVID-19 in gout arthritis patients. Further studies with a large number of patients are needed to confirm the above beneficial effect of colchicine.

Gout Pharmacotherapy in Cardiovascular Diseases: A Review of Utility and Outcomes.

Hyperuricemia and gout have been linked to an increased risk for cardiovascular (CV) disease, stroke, hypertension, heart failure, and chronic kidney disease, possibly through a proinflammatory milieu. However, not all the drugs used in gout treatment improve CV outcomes; colchicine has shown improved CV outcomes in patients with recent myocardial infarction and stable coronary artery disease independent of lipid-lowering effects. There is resurging interest in colchicine following publication of the COLCOT, LoDoCo, LoDoCo2, LoDoCo-MI trials, and COLCORONA trial which will shed light on its utility in COVID-19. Our aim is to review the CV use of colchicine beyond pericardial diseases, as well as CV outcomes of the available gout therapies, including allopurinol and febuxostat. The CARES trial and its surrounding controversies, which lead to the US FDA 'black box' warning on febuxostat, in addition to the recent FAST trial which contradicts this and finds febuxostat to be non-inferior, are discussed in this paper.

Successful Treatment of Covid-19 Associated Cytokine Release Syndrome with Colchicine. A Case Report and Review of Literature.

We describe the case of a 42 year old, healthy patient with Covid-19 who despite improvement in his respiratory symptoms developed a mild to moderate cytokine release syndrome (CRS) and an associated monoarticular gout flare. Since the patient refused admission to the hospital and had stable vital signs, we chose to treat him with a safe anti-inflammatory and non-immunosuppressive therapy. To hit two birds with one stone, we considered colchicine, as it has systemic anti-inflammatory effects and is also effective in gout flare. Unexpectedly, 48 hours after treatment, not only did his ongoing fever and toe pain disappear, he also had significant improvements in his general state of health and all his inflammatory markers including fibrinogen, ferritin, D-dimer, and IL-6 levels normalized. To our knowledge, the use of colchicine in Covid-19 and CRS has not been reported. This observation merits the consideration of colchicine as a safe, inexpensive and oral medication for the treatment of mild to moderate CRS in Covid-19 patients. More importantly, in Covid-19 patients with early lung involvement colchicine may be an appropriate candidate to prevent CRS in adjunction with routine antiviral agents. Indeed, multicenter, randomized controlled studies are required to evaluate the benefits of this therapy.