Comparative Analysis of Coagulation Activation in Rheumatoid Arthritis Patients Treated With TNF Inhibitors Versus JAK Inhibitors: A Prospective Study.

OBJECTIVES: This study aims to investigate the activation of the coagulation system of RA patients and assess changes during anti-inflammatory treatment with tumor necrosis factor blockers (anti-TNF) and Janus kinase inhibitors (JAKi). METHODS: Biomarkers for the coagulation system, including D-dimer, fibrinogen, prothrombin time, activated partial thrombin time, prothrombin fragment 1 + 2, thrombin-antithrombin complex (TAT), activated factor IX, antithrombin complex, and von Willebrand factor (vWF), were longitudinally measured in 83 RA patients treated with anti-TNF and 38 RA patients with JAKi. Data were collected at baseline, after 1, 3, and 6 months. RESULTS: The mean age was 57 (±14) years; 76% was female. The mean DAS28-CRP was 3.6 (±1.3) for anti-TNF users and 4.1 (±1.4) for JAKi users at baseline and declined in both groups. Baseline coagulation markers levels were comparable between groups. In anti-TNF users, D-dimer and fibrinogen levels significantly declined (-0.31 mg/L, p = 0.01 and -0.71 g/L, p < 0.001, respectively), whereas TAT significantly increased after 6 months follow-up (1.46 µg/L, p = 0.03) and no effect on vWF (p = 0.98). In JAKi users, vWF declined significantly during the 6 months follow-up (-37.41%, p < 0.001); additionally, there were reductions of D-dimer, fibrinogen, and TAT that did not reach significance (-0.17 mg/L, p = 0.59; -0.49 g/L, p = 0.12; and 0.68 µg/L, p = 0.27, respectively). CONCLUSIONS: The prothrombotic tendency in active RA declined during effective treatment with both anti-TNF and JAKi. Altogether, the biomarkers used in this study suggest that an increased VTE risk in the first 6 months due to either treatment with anti-TNF or JAKi is unlikely.

A multidisciplinary lifestyle program for metabolic syndrome-associated osteoarthritis: the "Plants for Joints" randomized controlled trial.

OBJECTIVE: To determine the effectiveness of the "Plants for Joints" multidisciplinary lifestyle program in patients with metabolic syndrome-associated osteoarthritis (MSOA). DESIGN: Patients with hip or knee MSOA were randomized to the intervention or control group. The intervention group followed a 16-week program in addition to usual care based on a whole food plant-based diet, physical activity, and stress management. The control group received usual care. The patient-reported Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) total score (range 0-96) was the primary outcome. Secondary outcomes included other patient-reported, anthropometric, and metabolic measures. An intention-to-treat analysis with a linear-mixed model adjusted for baseline values was used to analyze between-group differences. RESULTS: Of the 66 people randomized, 64 completed the study. Participants (84% female) had a mean (SD) age of 63 (6) years and body mass index of 33 (5) kg/m2. After 16 weeks, the intervention group (n = 32) had a mean 11-point larger improvement in WOMAC-score (95% CI 6-16; p = 0.0001) compared to the control group. The intervention group also lost more weight (-5 kg), fat mass (-4 kg), and waist circumference (-6 cm) compared to the control group. Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue, pain interference, C-reactive protein, hemoglobin A1c, fasting glucose, and low-density lipoproteins improved in the intervention versus the control group, while other PROMIS measures, blood pressure, high-density lipoproteins, and triglycerides did not differ significantly between the groups. CONCLUSION: The "Plants for Joints" lifestyle program reduced stiffness, relieved pain, and improved physical function in people with hip or knee MSOA compared to usual care.

Cardiovascular risk management in gout patients: do patients benefit from screening in secondary care?

OBJECTIVES: To estimate the 10-year cardiovascular disease (CVD) risk in gout patients in secondary care and to evaluate the effect of CVD risk screening on the 10-year CVD risk after 1 year. METHODS: A prospective cohort study was performed in patients with gout from Reade Amsterdam. Data on gout and CVD history, traditional risk factors, medication, and lifestyle were collected at baseline and 1 year. The 10-year CVD risk was calculated with the use of the NL-SCORE. A paired sample t-test and McNemar test was performed to test for differences between baseline and the 1-year visit. RESULTS: A very high prevalence of traditional CV risk factors was seen in our secondary care gout patients. Nineteen percent without previous CVD were categorised in the high-risk group according the NL-SCORE. The prevalence of CVD increased from 16% to 21% after 1-year follow-up. A decrease was seen in total- and LDL-cholesterol after 1 year. No decrease in mean BMI, waist-hip ratio, blood pressure or NL-SCORE was observed. CONCLUSIONS: The current need for CVD risk screening of gout patients in secondary care was illustrated by the high prevalence of traditional risk factors in this cohort. Recommendations to patients and the general practitioner (GP) alone did not result in overall improvement of traditional CVD risk factors nor the 10-year CVD risk. Our results indicate that a more prominent role of the rheumatologist is necessary to optimise the process of initiation and management of CVD risk in gout patients.

High-intensity versus low-intensity resistance training in patients with knee osteoarthritis: A randomized controlled trial.

OBJECTIVES: To assess whether (i) high-intensity resistance training (RT) leads to increased muscle strength compared to low-intensity RT in patients with knee osteoarthritis (OA); and (ii) RT with vitamin D supplementation leads to increased muscle strength compared to placebo in a subgroup with vitamin D deficiency. DESIGN: Randomized controlled trial. SETTING: Outpatient rehabilitation centre. SUBJECTS: Patients with knee OA. INTERVENTIONS: 12 weeks of RT at high-intensity RT (70-80% of 1-repetition maximum (1-RM)) or low-intensity RT (40-50% of 1-RM) and 24 weeks of vitamin D (1200 International units vitamin D3 per day) or placebo supplementation. MAIN MEASURES: Primary outcome measure was isokinetic muscle strength. Other outcome measure for muscle strength was the estimated 1-RM. Secondary outcome measures were knee pain and physical functioning. RESULTS: 177 participants with a mean age of 67.6 ± 5.8 years were included, of whom 50 had vitamin D deficiency. Isokinetic muscle strength (in Newton metre per kilogram bodyweight) at start, end and 24 weeks after the RT was 0.98 ± 0.40, 1.11 ± 0.40, 1.09 ± 0.42 in the high-intensity group and 1.02 ± 0.41, 1.15 ± 0.42, 1.12 ± 0.40 in the low-intensity group, respectively. No differences were found between the groups, except for the estimated 1-RM in favour of the high-intensity group. In the subgroup with vitamin D deficiency, no difference on isokinetic muscle strength was found between the vitamin D and placebo group. CONCLUSIONS: High-intensity RT did not result in greater improvements in isokinetic muscle strength, pain and physical functioning compared to low-intensity RT in knee OA, but was well tolerated. Therefore these results suggest that either intensity of resistance training could be utilised in exercise programmes for patients with knee osteoarthritis. No synergistic effect of vitamin D supplementation and RT was found, but this finding was based on underpowered data.

A neutrophil signature is strongly associated with increased cardiovascular risk in gout.

OBJECTIVE: To investigate the association between neutrophil activation and cardiovascular risk in gout patients. We hypothesize that neutrophil activation mediates inflammation and therefore takes part in atherogenesis in gout patients. METHOD: Patient data were collected from 75 consecutive gout patients participating in the Reade gout cohort Amsterdam. Levels of neutrophil extracellular traps (NETs) and neutrophil activation (calprotectin and peroxidase activity) were analysed by ELISA and fluorimetry in plasma and compared with healthy controls. Markers of neutrophil activation were related to clinical markers of cardiovascular risk, including BMI, smoking, blood pressure, lipid profile and 10 year risk of cardiovascular mortality (EU-SCORE). RESULTS: Increased levels of NETs were found in gout patients, although increased levels were not associated with cardiovascular risk. However, markers of neutrophil activation, including peroxidase activity correlated with waist:hip ratio (ß = 0.33, P < 0.001), cholesterol ratio (ß = 0.46, P < 0.005) and triglycerides (ß = 0.60, P < 0.001) as well as the 10 year risk of cardiovascular mortality (ß = 0.44, P = 0.001). Calprotectin levels were elevated in hypertension (P = 0.005) and diabetes (P = 0.02). Finally, gout patients with high levels of both peroxidase and calprotectin ('neutrophil activation signature') had a markedly elevated cardiovascular risk score (P = 0.001), with 68% of the patients having high cardiovascular risk (odds ratio 2.9, P = 0.03). CONCLUSION: We demonstrated elevated levels of neutrophil activation markers, MPO and calprotectin in gout patients as compared with healthy controls. Of note, neutrophil activation markers were associated with several risk factors for cardiovascular disease, including hyperlipidaemia, hypertension and diabetes. Finally, the presence of a neutrophil activation signature was strongly associated with an increased 10 year risk of cardiovascular mortality. Further studies are needed to determine whether gout-specific factors and/or cardiovascular risk factors contribute to the elevated neutrophil activation observed in these patients.

Which factors predict discordance between a patient and physician on a gout flare?

OBJECTIVE: To investigate the factors associated with discordance between patient and physician on the presence of a gout flare. METHODS: Patients' self-reports of current gout flares were assessed with the question, 'Are you having a gout flare today?' which was then compared with a concurrent, blinded, physician's assessment. Based on agreement or disagreement with physicians on the presence of a gout flare, flares were divided into concordant and discordant groups, respectively. Within the discordant group, two subgroups-patient-reported flare but the physician disagreed and physician-reported flare but the patient disagreed-were identified. The factors associated with discordance were analysed with multivariable logistic regression analysis. RESULTS: Of 268 gout flares, 81 (30.2%) flares were discordant, with either patient or physician disagreeing on the presence of a flare. Of the discordant flares, in 57 (70.4%) the patient reported a flare but the physician disagreed. In multivariable logistic regression analysis adjusted for demographics, disagreement among patients and physicians on the presence of a gout flare was associated with lower pain scores at rest [odds ratio (OR) for each point increase on 0-10 point pain scale 0.81 (95% Wald CI 0.73, 0.90), P < 0.0001] and less presence of joint swelling [OR 0.24 (95% CI 0.10, 0.61), P = 0.003] or joint warmth [OR 0.39 (95% CI 0.20, 0.75), P = 0.005]. CONCLUSION: Although patients and physicians generally agree about the presence of gout flare, discordance may occur in the setting of low pain scores and in the absence of swollen or warm joints.

Performance of classification criteria for gout in early and established disease.

OBJECTIVES: To compare the sensitivity and specificity of different classification criteria for gout in early and established disease. METHODS: This was a cross-sectional study of consecutive rheumatology clinic patients with joint swelling in which gout was defined by presence or absence of monosodium urate crystals as observed by a certified examiner at presentation. Early disease was defined as patient-reported onset of symptoms of 2 years or less. RESULTS: Data from 983 patients were collected and gout was present in 509 (52%). Early disease was present in 144 gout cases and 228 non-cases. Sensitivity across criteria was better in established disease (95.3% vs 84.1%, p<0.001) and specificity was better in early disease (79.9% vs 52.5%, p<0.001). The overall best performing clinical criteria were the Rome criteria with sensitivity/specificity in early and established disease of 60.3%/84.4% and 86.4%/63.6%. Criteria not requiring synovial fluid analysis had sensitivity and specificity of less than 80% in early and established disease. CONCLUSIONS: Existing classification criteria for gout have sensitivity of over 80% in early and established disease but currently available criteria that do not require synovial fluid analysis have inadequate specificity especially later in the disease. Classification criteria for gout with better specificity are required, although the findings should be cautiously applied to non-rheumatology clinic populations.

The Effects of Pharmacological Urate-Lowering Therapy on Cardiovascular Disease in Older Adults with Gout.

Cardiovascular disease is an important cause of mortality in older patients. In addition to the traditional risk factors for cardiovascular disease, hyperuricemia has been increasingly associated with an elevated risk of cardiovascular disease. Uric acid itself has several unfavorable effects on the cardiovascular system, and hyperuricemia can lead to the development of gout. Gout is the most prevalent inflammatory rheumatic disease. Older patients with gout have an increased risk of cardiovascular morbidity and mortality due to an increased prevalence of traditional risk factors, as well as the inflammatory burden of gout activity. As the prevalence of traditional risk factors and the prevalence of both hyperuricemia and gout are increasing in older adults, cardiovascular risk management in these patients is very important. This risk management consists of, on the one hand, treatment of individual traditional risk factors and, on the other hand, of urate lowering, thereby decreasing inflammatory burden of gout. However, there is insufficient evidence to conclude that urate-lowering therapy reduces the risk of cardiovascular events. Moreover, from a cardiovascular point of view, there is no preference for one urate lowering drug over another in patients with gout, nor is there enough evidence to support a preference in patients with gout with increased cardiovascular risk. Personalized treatment in older patients with gout should be aimed at optimizing serum uric acid levels, as well as targeting traditional cardiovascular risk factors. Further prospective randomized trials are needed to support the hypothesis that urate lowering reduces cardiovascular risk in older patients with gout.

Long-term effectiveness of a lifestyle intervention for rheumatoid arthritis and osteoarthritis: 1-year follow-up of the 'Plants for Joints' randomised clinical trial.

OBJECTIVES: In two randomised controlled trials, the Plants for Joints (PFJ) multidisciplinary lifestyle intervention reduced signs and symptoms of rheumatoid arthritis (RA), or metabolic syndrome-associated hip or knee osteoarthritis (MSOA) compared with usual care. The current study investigated long-term outcomes. METHODS: After completion of two 16-week trials in people with (1) RA or (2) MSOA, control groups switched to the active PFJ intervention. At the end of the intervention, all participants were followed up in a 1-year observational extension study. Primary outcomes were 28-joint Disease Activity Score (DAS28) (RA) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (MSOA). Secondary outcomes included body composition, metabolic outcomes, medication changes and intervention adherence. An intention-to-treat analysis with a linear mixed model was used to analyse within-group changes. RESULTS: 65 (84%) of 77 RA participants and 49 (77%) of 64 MSOA participants completed the extension study. The effects of the PFJ intervention were replicated in the original control groups and sustained within the RA group a year after intervention completion (mean DAS28 -0.9 points; p<0.001), while in the MSOA group mean WOMAC increased towards but remained well under the starting value (-7.8 points, p<0.001). Improvements in C-reactive protein, waist circumference (RA and MSOA); low-density lipoprotein cholesterol (RA); and weight, haemoglobin A1c, blood pressure (MSOA) were also sustained. Participants had a net decrease of medication, and intervention adherence was largely sustained. CONCLUSIONS: A year after the PFJ lifestyle intervention, improvements of disease activity and metabolic outcomes within RA and MSOA groups were largely sustained and related to sustained adherence, with a net decrease of medication. TRIAL REGISTRATION NUMBERS: NL7800, NL7801.

Patient-perspective and feasibility of home finger-prick testing to complement and facilitate large-scale research in rheumatology.

BACKGROUND: During the COVID-19 pandemic, we developed a digital research platform to longitudinally investigate COVID-19-related outcomes in patients with rheumatic diseases and healthy controls. We used home finger-prick testing in order to collect serum samples remotely and increase the overall efficiency of the platform. The aim of the present study was to evaluate the success rate of the finger prick and patients' perspective towards the finger prick. METHODS: Serum samples were collected up to five times during follow-up, either via a venepuncture at the research institute or a finger prick from participants' home. Participants were asked to complete a digital evaluation questionnaire of the finger prick after their attempts. RESULTS: A total of 2135 patients and 899 controls performed at least one finger prick and were included in this study. The first finger prick was successfully done by 92% (95% CI: 90% to 93%) of patients, 94% (95% CI: 92% to 95%) of controls, 93% (95% CI: 92% to 94%) of all participants aged ≤70 years and 89% (95% CI: 86% to 92%) of all participants aged >70 years. Sex did not impact these success rates. Repeated failure occurred in 11/439 (0.8%) patients and 4/712 (0.6%) controls. Both patients and controls were less willing to perform a finger prick for individual healthcare compared with scientific research. CONCLUSION: The vast majority of participants, among which elderly and patients with rheumatic diseases, were able to successfully draw the required amount of blood for serological analyses. This shows that finger-prick testing is suitable for a high-throughput implementation to monitor patients remotely.

Association of serum C-reactive protein and erythrocyte sedimentation rate with muscle strength in patients with knee osteoarthritis.

OBJECTIVE: To examine the association of serum CRP and ESR with muscle strength in patients with knee OA. METHODS: Cross-sectional data from 285 patients with knee OA from the Amsterdam Osteoarthritis (AMS-OA) cohort were analysed. CRP (mg/l) and ESR (mm/l) were measured in serum from patients' blood samples and the values were dichotomized for the analyses. Strength of quadriceps and hamstring muscles was assessed using an isokinetic dynamometer. Univariable and multivariable linear regression analyses were used to assess the association of CRP and ESR with muscle strength, adjusting for relevant confounders. RESULTS: Elevated levels of serum CRP (ß = -0.10; P = 0.04) and ESR (ß = -0.12; P = 0.02) were associated with lower muscle strength after adjustment for age, sex, comorbidities and NSAID use. The associations were no longer significant when BMI was incorporated in the adjusted model. CONCLUSION: Inflammation might influence muscle strength in patients with knee OA. Moreover, the link between inflammation and obesity might explain the effect that BMI has in the associations between inflammatory markers (i.e. CRP and ESR) and muscle strength.

Post-COVID condition in patients with inflammatory rheumatic diseases: a prospective cohort study in the Netherlands.

Background: Studies on long-term consequences of COVID-19, commonly referred to as post-COVID condition, in patients with inflammatory rheumatic diseases are scarce and inconclusive. Furthermore, classifying patients with inflammatory rheumatic diseases as having post-COVID condition is complicated because of overlapping symptoms. Therefore, we investigated the risk of post-COVID condition and time until recovery, and compared the prevalence of symptoms seen in post-COVID condition, between patients with inflammatory rheumatic diseases and healthy controls, with and without a history of COVID-19. Methods: In this substudy we used data from an ongoing prospective cohort study in the Netherlands. All adult patients with inflammatory rheumatic diseases from the Amsterdam Rheumatology and Immunology Center in Amsterdam, the Netherlands, were invited to participate in the study between April 26, 2020, and March 1, 2021. All patients were asked, but not obliged, to recruit their own control participant of the same sex, of comparable age (< 5 years), and without an inflammatory rheumatic disease. Demographic and clinical data, including data on the occurrence of SARS-CoV-2 infections, were collected via online questionnaires. On March 10, 2022, all study participants received a questionnaire on the occurrence, onset, severity, and duration of persistent symptoms during the first 2 years of the COVID-19 pandemic, independent of their history of SARS-CoV-2 infection. Additionally, we prospectively monitored a subset of participants who had a PCR or antigen confirmed SARS-CoV-2 infection in the 2-month period surrounding the questionnaire in order to assess COVID-19 sequelae. In line with WHO guidelines, post-COVID condition was defined as persistent symptoms that lasted at least 8 weeks, started after the onset and within 3 months of a PCR or antigen-confirmed SARS-CoV-2 infection, and could not be explained by an alternative diagnosis. Statistical analyses included descriptive statistics, logistic regression analyses, logistic-based causal mediation analyses, and Kaplan-Meier survival analyses for time until recovery from post-COVID condition. In exploratory analyses, E-values were calculated to investigate unmeasured confounding. Findings: A total of 1974 patients with inflammatory rheumatic disease (1268 [64%] women and 706 [36%] men; mean age 59 years [SD 13]) and 733 healthy controls (495 [68%] women and 238 [32%] men; mean age 59 years [12]) participated. 468 (24%) of 1974 patients with inflammatory rheumatic disease and 218 (30%) of 733 healthy controls had a recent SARS-CoV-2 omicron infection. Of those, 365 (78%) of 468 patients with inflammatory rheumatic disease and 172 (79%) of 218 healthy controls completed the prospective follow-up COVID-19 sequelae questionnaires. More patients than controls fulfilled post-COVID condition criteria: 77 (21%) of 365 versus 23 (13%) of 172 (odds ratio [OR] 1·73 [95% CI 1·04-2·87]; p=0·033). The OR was attenuated after adjusting for potential confounders (adjusted OR 1·53 [95% CI 0·90-2·59]; p=0·12). Among those without a history of COVID-19, patients with inflammatory diseases were more likely to report persistent symptoms consistent with post-COVID condition than were healthy controls (OR 2·52 [95% CI 1·92-3·32]; p<0·0001). This OR exceeded the calculated E-values of 1·74 and 1·96. Recovery time from post-COVID condition was similar for patients and controls (p=0·17). Fatigue and loss of fitness were the most frequently reported symptoms in both patients with inflammatory rheumatic disease and healthy controls with post-COVID condition. Interpretation: Post-COVID condition after SARS-CoV-2 omicron infections was higher in patients with inflammatory rheumatic disease than in healthy controls based on WHO classification guidelines. However, because more patients with inflammatory rheumatic disease than healthy controls without a history of COVID-19 reported symptoms that are commonly used to define a post-COVID condition during the first 2 years of the pandemic, it is likely that the observed difference in post-COVID condition between patients and controls might in part be explained by clinical manifestations in the context of underlying rheumatic diseases. This highlights the limitations of applying current criteria for post-COVID condition in patients with inflammatory rheumatic disease, and suggests it might be appropriate for physicians to keep a nuanced attitude when communicating the long-term consequences of COVID-19. Funding: ZonMw (the Netherlands organization for Health Research and Development) and Reade foundation.

Coagulation in gout: is there a link with disease activity?

OBJECTIVE: To investigate the coagulation system in gout patients and associations between disease activity and levels of coagulation markers. METHODS: A prospective cohort study was performed with data from 30 Dutch gout patients. Levels of coagulation markers including APTT, PT, D-dimer, prothrombin F1 + 2, von Willebrand factor, and thrombin generation parameters were analyzed at baseline and 1-year visit. These markers were related to clinical markers of gout disease activity including the Gout Activity Score (GAS). Our hypothesis was that patients with gout and active disease have increased levels of coagulation markers and that a decrease in disease activity would lead to normalization of coagulation activity. RESULTS: A higher GAS was associated with increased levels of thrombin generation parameters including ETP (ß = 0.48, p = 0.01), peak thrombin (ß = 0.60, p = 0.001), and velocity index (ß = 0.57, p = 0.002). Tophaceous gout and higher SUA levels were associated with thrombin generation parameters. After 1 year, thrombin generation parameters showed a small procoagulant trend despite a moderate decrease in disease activity. Prospectively measured changes in disease activity according to the GAS were not associated with any of the coagulation markers. CONCLUSION: Patients with active gout have higher levels of thrombin generation markers, indicating a link between disease activity and coagulation. A change in disease activity after 1 year was not associated with significant changes in coagulation markers, probably due to prolonged low-grade inflammation. Future studies should focus on levels of coagulation markers in comparison with the general population and the effect of adequate gout treatment. Key Points • Patients with gout have an increased risk of cardiovascular events. • High disease activity was associated with higher levels of thrombin generation markers. • Over time, small decreases in inflammation were associated with a decrease in D-dimer and thrombin generation.

Effects of intensive urate lowering therapy with febuxostat in comparison with allopurinol on pulse wave velocity in patients with gout and increased cardiovascular risk: the FORWARD study.

AIMS: Hyperuricaemia and gout are strongly related with traditional cardiovascular risk factors and vascular damage. This study aimed to assess whether febuxostat and allopurinol could differently influence carotid-femoral pulse wave velocity (cfPWV) in patients with gout and elevated serum uric acid (SUA) levels. METHODS AND RESULTS: A multi-centre, multinational, phase IV, randomized, parallel-group, active-controlled, open-label trial with blind endpoints evaluation. One hundred and ninety-seven adults with gout and SUA levels ≥8 mg/dL were randomized to febuxostat or allopurinol in a 1:1 ratio for 36 weeks. The primary outcome was the comparison of the effects of febuxostat and allopurinol on changes in cfPWV. The mean cfPWV values at randomization and Week 36 were 8.69 and 9.00 m/s, respectively for subjects randomized to febuxostat and 9.02 and 9.05 m/s for subjects randomized to allopurinol. No statistically significant changes in cfPWV by treatment assignment were observed at any time point for any of the assessed parameters. More subjects who received febuxostat had serum urate concentrations ≤6 mg/dL following treatment (78.3% vs. 61.1% at Week 36, P = 0.0137). Treatment-emergent adverse events were reported by 51 (52.0%) patients randomized to febuxostat and 63 (62.5%) patients randomized to allopurinol. The majority of events were mild in both treatment groups and included gout flares and arthralgia. CONCLUSION: In patients with gout and elevated SUA levels the arterial stiffness remained stable both with febuxostat and allopurinol. Febuxostat was more effective and faster than allopurinol in achieving the SUA target. Both treatments were safe and well tolerated.

Antibody development and disease severity of COVID-19 in non-immunised patients with rheumatic immune-mediated inflammatory diseases: data from a prospective cohort study.

BACKGROUND: Research on the disease severity of COVID-19 in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) has been inconclusive, and long-term prospective data on the development of SARS-CoV-2 antibodies in these patients are lacking. METHODS: Adult patients with rheumatic IMIDs from the Amsterdam Rheumatology and Immunology Center, Amsterdam were invited to participate. All patients were asked to recruit their own sex-matched and age-matched control subject. Clinical data were collected via online questionnaires (at baseline, and after 1-4 and 5-9 months of follow-up). Serum samples were collected twice and analysed for the presence of SARS-CoV-2-specific antibodies. Subsequently, IgG titres were quantified in samples with a positive test result. FINDINGS: In total, 3080 consecutive patients and 1102 controls with comparable age and sex distribution were included for analyses. Patients were more frequently hospitalised compared with controls when infected with SARS-CoV-2; 7% vs 0.7% (adjusted OR: 7.33, 95% CI: 0.96 to 55.77). Only treatment with B-cell targeting therapy was independently associated with an increased risk of COVID-19-related hospitalisation (adjusted OR: 14.62, 95% CI: 2.31 to 92.39). IgG antibody titres were higher in hospitalised compared with non-hospitalised patients, and slowly declined with time in similar patterns for patients in all treatment subgroups and controls. INTERPRETATION: We observed that patients with rheumatic IMIDs, especially those treated with B-cell targeting therapy, were more likely to be hospitalised when infected with SARS-CoV-2. Treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and biological DMARDs other than B-cell targeting agents is unlikely to have negative effects on the development of long-lasting humoral immunity against SARS-CoV-2.

Validation of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: slight improvement over the 1987 ACR criteria.

BACKGROUND: Recently, an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) collaboration developed new classification criteria for rheumatoid arthritis (RA). OBJECTIVE: To evaluate the diagnostic and discriminative ability of these new criteria compared with the 1987 ACR criteria and the Visser decision rule. METHODS: 455 patients with early arthritis were studied. The diagnostic performance of the criteria was evaluated using methotrexate treatment within 1 year, expert opinion RA and erosive disease as 'gold standards'. Erosive disease was defined as a 0-3 year change in radiographic score of ≥5. RESULTS: The discriminative ability of the three criteria sets (2010 ACR/EULAR, 1987 ACR criteria and Visser algorithm) was similar with areas under the curve of 0.71-0.78 ('gold standard' methotrexate), 0.74-0.80 (gold standard expert opinion RA) and 0.63-0.67 (gold standard erosive disease after 3 years). The sensitivity of the 2010 ACR/EULAR criteria was highest with 0.85 (gold standard methotrexate). 86% of patients with RA and 51% of 'non-RA' patients according to the new criteria used methotrexate. CONCLUSION: The 2010 ACR/EULAR criteria were slightly more sensitive, but otherwise performed similarly to the older criteria. A high percentage of 'non-RA' patients used methotrexate, the gold standard for RA. The ability of the new criteria to identify patients with erosive disease was low, possibly owing to the effect of intensive treatment.

Cardiovascular risk in inflammatory arthritis: rheumatoid arthritis and gout.

The increased risk of cardiovascular morbidity and mortality in rheumatoid arthritis and gout has been increasingly acknowledged in past decades, with accumulating evidence that gout, just as with rheumatoid arthritis, is an independent cardiovascular risk factor. Although both diseases have a completely different pathogenesis, the underlying pathophysiological mechanisms in systemic inflammation overlap to some extent. Following the recognition that systemic inflammation has an important causative role in cardiovascular disease, anti-inflammatory therapy in both conditions and urate-lowering therapies in gout are expected to lower the cardiovascular burden of patients. Unfortunately, much of the existing data showing that urate-lowering therapy has consistent beneficial effects on cardiovascular outcomes in patients with gout are of low quality and contradictory. We will discuss the latest evidence in this respect. Cardiovascular disease risk management for patients with rheumatoid arthritis and gout is essential. Clinical guidelines and implementation of cardiovascular risk management in daily clinical practice, as well as unmet needs and areas for further investigation, will be discussed.

Dietary Interventions for Gout and Effect on Cardiovascular Risk Factors: A Systematic Review.

Gout is one of the most prevalent inflammatory rheumatic disease. It is preceded by hyperuricemia and associated with an increased risk for cardiovascular disease, both related to unhealthy diets. The objective of this systematic review is to better define the most appropriate diet addressing both disease activity and traditional cardiovascular risk factors in hyperuricemic patients. We included clinical trials with patients diagnosed with hyperuricemia or gout, investigating the effect of dietary interventions on serum uric acid (SUA) levels, gout flares and-if available-cardiovascular risk factors. Eighteen articles were included, which were too heterogeneous to perform a meta-analysis. Overall, the risk of bias of the studies was moderate to high. We distinguished four groups of dietary interventions: Calorie restriction and fasting, purine-low diets, Mediterranean-style diets, and supplements. Overall, fasting resulted in an increase of SUA, whilst small (SUA change +0.3 to -2.9 mg/dL) but significant effects were found after low-calorie, purine-low, and Mediterranean-style diets. Studies investigating the effect on cardiovascular risk factors were limited and inconclusive. Since Mediterranean-style diets/DASH (Dietary Approach to Stop Hypertension) have shown to be effective for the reduction of cardiovascular risk factors in other at-risk populations, we recommend further investigation of such diets for the treatment of gout.

Brief Report: Validation of a Definition of Flare in Patients With Established Gout.

OBJECTIVE: To perform external validation of a provisional definition of disease flare in patients with gout. METHODS: Five hundred nine patients with gout were enrolled in a cross-sectional study during a routine clinical care visit at 17 international sites. Data were collected to classify patients as experiencing or not experiencing a gout flare, according to a provisional definition. A local expert rheumatologist performed the final independent adjudication of gout flare status. Sensitivity, specificity, predictive values, and receiver operating characteristic (ROC) curves were used to determine the diagnostic performance of gout flare definitions. RESULTS: The mean ± SD age of the patients was 57.5 ± 13.9 years, and 89% were male. The definition requiring fulfillment of at least 3 of 4 criteria (patient-defined gout flare, pain at rest score of >3 on a 0-10-point numerical rating scale, presence of at least 1 swollen joint, and presence of at least 1 warm joint) was 85% sensitive and 95% specific in confirming the presence of a gout flare, with an accuracy of 92%. The ROC area under the curve was 0.97. The definition based on a classification and regression tree algorithm (entry point, pain at rest score >3, followed by patient-defined flare "yes") was 73% sensitive and 96% specific. CONCLUSION: The definition of gout flare that requires fulfillment of at least 3 of 4 patient-reported criteria is now validated to be sensitive, specific, and accurate for gout flares, as demonstrated using an independent large international patient sample. The availability of a validated gout flare definition will improve the ascertainment of an important clinical outcome in studies of gout.