Effect of metformin use on clinical outcomes and serum urate in gout patients with diabetes mellitus: a retrospective cohort study.

OBJECTIVE: Gout and diabetes mellitus type 2 (DM) frequently co-exist. The pharmacological effects of metformin may include anti-inflammatory and urate lowering effects. The objective of this study was to test these effects in patients with gout starting uric acid lowering treatment (ULT) in secondary care. METHODS: Retrospective cohort study including patients with gout and DM starting ULT. Differences in the incidence density of gout flares, proportion of patients reaching target sUA in the first six months after starting ULT, and difference in mean allopurinol dose at sUA target were compared between users of metformin and users of other or no anti-diabetic drugs (control group). Correction for confounding was applied. RESULTS: A total of 307 patients were included, of whom 160 (52.1%) used metformin. The incidence of flares was 1.61 and 1.70 in the first six months for respectively the metformin group and control group. The incidence rate ratio for gout flares was not significant (0.95, 95% CI 0.78 to 1.14). At six months, 62.8% and 54.9% reached target sUA in the metformin and control group respectively, corrected odds ratio of 1.09 (95% CI 0.66 to 1.80). There was no difference in mean allopurinol dose at sUA target 266 mg for metformin users and 236 mg for the control group, difference 30 mg (95% CI - 4.7 to 65.5). CONCLUSIONS: In conclusion we could not confirm a clinically relevant anti-inflammatory or urate lowering effect of metformin in patients starting ULT treatment and receiving usual care flare prophylaxis.

Younger age and female gender are determinants of underestimated cardiovascular risk in rheumatoid arthritis patients: a prospective cohort study.

BACKGROUND: Rheumatoid arthritis (RA) patients have an increased cardiovascular (CV) risk. Here, we aimed to investigate whether gender and age are contributing to the misclassification of CV risk in RA patients. METHODS: Prospectively collected data on cardiovascular risk factors and incident events from the Nijmegen inception cohort were analyzed, with up to 10 years follow-up. Original as well as the EULAR-modified (M)_SCORE algorithms were used to calculate CV risk. Patients were stratified in deciles according to predicted risk; the Hosmer-Lemeshow test was used to check concordance between observed and predicted risk, in subgroups of gender and age. RESULTS: There were 863 RA patients included with 128 incident CV events. When using SCORE in the whole group, there was evidence of a discrepancy between the predicted and observed CV risk (H-L test p < 0.003), mainly present in the female subgroup (H-L test p < 0.001). Interestingly, 36% of females who developed an event belonged to the low CV risk group, whereas this was just 10% in RA males. When analyzing the subgroups based on age, a discrepancy was present only in the youngest patients (H-L test p < 0.001 in patients < 55 years) consisting of an underestimation of CV risk (5.3% predicted vs. 8.0% observed). Similar results were obtained when the M_SCORE was applied. CONCLUSION: CV risk is especially underestimated in female and younger RA patients. This suggests that modifying the weight for the female gender and/or younger age in currently used CV risk algorithms might improve their predictive value in RA, contributing to better CV risk management.

Stopping Tumor Necrosis Factor Inhibitor Treatment in Patients With Established Rheumatoid Arthritis in Remission or With Stable Low Disease Activity: A Pragmatic Multicenter, Open-Label Randomized Controlled Trial.

OBJECTIVE: Tumor necrosis factor inhibitor (TNFi) biologic agents are an effective treatment for rheumatoid arthritis (RA). It is unclear whether patients whose disease is in remission or who have stable low disease activity need to continue use of TNFi or can stop this treatment. This study was undertaken to assess whether patients with established RA who are in remission or have stable low disease activity can effectively and safely stop their TNFi therapy. METHODS: The study was designed as a pragmatic multicenter, open-label randomized controlled trial. Inclusion criteria were a diagnosis of RA according to the American College of Rheumatology 1987 classification criteria, as well as use of a TNFi for at least 1 year along with a stable dose of disease-modifying antirheumatic drugs and a Disease Activity Score in 28 joints (DAS28) of <3.2 over the 6 months preceding trial inclusion. Patients were randomized in a 2:1 ratio to either stop or continue treatment with their current TNFi. Flare was defined as a DAS28 of ≥3.2 during the 12-month follow-up period and an increase in score of ≥0.6 compared to the baseline DAS28. RESULTS: In total, 531 patients were allocated to the stop group and 286 to the TNFi continuation group. At 12 months, more patients had experienced a flare in the stop group (272 [51.2%] of 531) than in the continuation group (52 [18.2%] of 286; P < 0.001). The hazard ratio for occurrence of a flare after stopping TNFi was 3.50 (95% confidence interval [95% CI] 2.60-4.72). The mean DAS28 in the stop group was significantly higher during the follow-up period compared to that in the continuation group (P < 0.001). Of the 195 patients who restarted TNFi treatment after experiencing a flare and within 26 weeks after stopping, 165 (84.6%) had regained a DAS28 of <3.2 by 6 months later, and the median time to a regained DAS28 of <3.2 was 12 weeks (95% Cl 10.7-13.3). There were more hospitalizations in the stop group than in the continuation group (6.4% versus 2.4%). CONCLUSION: Stopping TNFi treatment results in substantially more flares than does continuation of TNFi in patients with established RA in remission or with stable low disease activity.

[Systemic sclerosis: a multisystem disease]. / Systemische sclerose: multisysteemaandoening.

Systemic sclerosis is a rare, systemic autoimmune disease, characterized by inflammation, vasculopathy and fibrosis of the skin and internal organs. The disease is associated with a significantly increased morbidity and mortality, and can be rapidly progressive. Interstitial lung disease, renal hypertensive crisis, cardiac involvement and pulmonary arterial hypertension are life-threatening complications. Early treatment with immunosuppressive drugs can prevent progression and decrease morbidity and mortality.

Hyperuricaemia: a marker of increased cardiovascular risk in rheumatic patients: analysis of the ACT-CVD cohort.

BACKGROUND: Gout and hyperuricaemia may be associated with increased cardiovascular risk, but analyses in different populations show conflicting results. This study investigates the impact of serum uric acid, inflammation and traditional CV risk parameters on CV event risk in patients with gouty arthritis and patients with non-gouty rheumatic disease. METHODS: cross-sectional and prospective multivariate analysis of the relation between tertiles of serum uric acid and individual traditional CV risk factors in a cohort of gouty arthritis (GA, n=172), rheumatoid arthritis (RA, n=480) and osteoarthritis (OA, n=206) patients. MAIN OUTCOME MEASURES: systolic blood pressure, TC/HDL ratio, GlyHb, BMI and first CV events. RESULTS: Individual CV risk factors were significantly less favourable in GA (systolic blood pressure, TC/HDL ratio, BMI, p<0.05). In RA and OA, but not in GA, individual cardiometabolic parameters correlated with serum uric acid values (OA: RA: systolic blood pressure, TC/HDL ratio, BMI; systolic blood pressure, TC/HDL ratio, GlyHb, BMI; p<0.05). In non-GA individuals the highest tertile of serum uric acid (>0.34 mmol/L) and NT proBNP level were independent predictors of first CV events, against age and GlyHb level in GA (p<0.05). The hazard of first CV events was equally significantly increased in GA patients (HR 3.169, 95% CI 1.287-7.806) and non-GA individuals with a serum uric acid ≥ 0.34 mmol/L (HR 3.721, 95% CI 1.603-8.634) compared to non-GA individuals with a serum uric acid < 0.27. CONCLUSIONS: GA is associated with a 3.1-fold hazard of first CV events. In non-GA rheumatic patients increasing serum uric acid is associated with increased CV risk, whereas CV risk in GA is independent of serum uric acid values. The presence of GA or a baseline serum uric acid in the upper range are possibly stronger predictors of first CV events than some traditional CV risk factors or parameters of inflammation.

Cardiovascular case fatality in rheumatoid arthritis is decreasing; first prospective analysis of a current low disease activity rheumatoid arthritis cohort and review of the literature.

BACKGROUND: Previous studies found increased case fatality after myocardial infarction and more frequent sudden death in RA patients compared to non-RA subjects. The RA associated CV risk might be explained by the combined effects of chronic systemic inflammation and increased lifestyle associated cardiovascular risk factors, and modified by the use of medication such as non steroidal anti-inflammatory drugs, corticosteroids and disease modifying anti-rheumatic drugs. Trends in case fatality rate in RA after the introduction of potent anti-inflammatory biologic therapies and treat-to-target treatment strategies aiming at remission are not known. This study was performed to examine the cardiovascular fatality rate in current low disease activity RA, and to evaluate trends in RA associated CV case fatality over time. METHODS: Prospective study to determine the incidence of fatal and nonfatal CV events in 480 RA patients included in the ACT-CVD cohort between February 2009 and December 2011. Patients with prior CV disease were excluded. Cox regression analysis was performed to determine CV event risk and contributing risk factors over time. The results of the cohort analysis were put into the context of a review of the literature to evaluate trends in RA associated CV fatality rate over time. RESULTS: The study included 480 RA patients, 72.3% female with median disease duration of 4.2 years, 72.1% being in clinical remission (Disease Activity Score in 28 joints). During a mean follow up of 2.9 years 29 patients (6%) experienced a first CV event, 2 fatal and 27 non-fatal, corresponding to a 6.9% case fatality rate. Comparison with previous studies in cohorts with successive enrolment periods shows a trend towards a decrease in CV case fatality in RA from 52.9% in 1998 to 6.9% in our study. CONCLUSION: CV case fatality in current low disease activity RA is importantly lower than in previous studies, and a trend towards decreasing CV fatality in RA is suggested.

[A woman with an eschar]. / Een vrouw met een eschar.

A 65-year-old woman had an eschar after a holiday to Spain. A skin biopsy showed findings consistent with an ulcer but tested negative for fungi, atypical mycobacteria and Leishmania parasites. Rickettsia conorii serology was negative. The diagnosis necrotic arachnidism was made based on the clinical picture.

Increased cardiovascular risk factors in different rheumatic diseases compared with the general population.

OBJECTIVES: To study the prevalence of cardiovascular risk factors among patients attending a rheumatology outpatient clinic in comparison with the general population. METHODS: Cross-sectional comparison between a rheumatic outpatient cohort of consecutive patients (n = 1233) between 36 and 75 years of age attending the Arthritis Center Twente (ACT) in the year 2009: RA (n = 546), gout (n = 129), OA (n = 168), CTD (n = 85), PMR (n = 91) and chronic localized or generalized pain syndromes (CPSs; n = 214) and a random sample from a long-lasting population-based health study in the Netherlands (n = 4523). The main outcome measures were hypertension (systolic blood pressure ≥ 140 mmHg and/or a diastolic blood pressure ≥ 90 mmHg and/or the use of antihypertensive medication), abnormal cholesterol profile (total cholesterol ≥ 6.5 mmol/l, and/or high-density lipoprotein < 0.9 mmol/l and/or use of lipid lowering medication), overweight (BMI ≥ 25 kg/m(2)), obesity (BMI ≥ 30 kg/m(2)) and cigarette smoking habits (self-reported current smoking). RESULTS: Compared with the general population, patients with rheumatic diseases have a significantly higher prevalence of hypertension (P(ACT) = 68%, P(general) = 57%), being overweight (P(ACT) = 72%, P(general) = 62%), obesity (P(ACT) = 30%, P(general) = 17%) and cigarette smoking (P(ACT) = 26%, P(general) = 21%). The worst risk profile was found in gout patients, with higher prevalence of all cardiovascular risk factors studied. CONCLUSION: Lifestyle-associated potentially modifiable cardiovascular risk factors are over-represented along the whole spectrum of chronic rheumatic diseases, and not only in RA, as suggested by preceding studies.

Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks.

While aspirin may offer protection, other non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) can cause serious cardiovascular side effects and complications. This has led to a general "black box" warning for cardiovascular adverse events for NSAIDs. This review explores the different mechanisms underlying the protective effects of aspirin, the NSAID associated renovascular effects causing hypertension, edema and heart failure, the cardiovascular effects causing myocardial infarction and stroke, and the possible deleterious interaction between NSAIDs and aspirin.