Harald E. Vonkeman

Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring: results of an international, cross-sectional study (COMORA)

Background Patients with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions. Objectives To evaluate the prevalence of comorbidities and compare their management in RA patients from different countries worldwide. Methods Study design: international, cross-sectional. Patients: consecutive RA patients. Data collected: demographics, disease characteristics (activity, severity, treatment), comorbidities (cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and psychiatric disorders). Results Of 4586 patients recruited in 17 participating countries, 3920 were analysed (age, 56±13 years; disease duration, 10±9 years (mean±SD); female gender, 82%; DAS28 (Disease Activity Score using 28 joints)–erythrocyte sedimentation rate, 3.7±1.6 (mean±SD); Health Assessment Questionnaire, 1.0±0.7 (mean±SD); past or current methotrexate use, 89%; past or current use of biological agents, 39%. The most frequently associated diseases (past or current) were: depression, 15%; asthma, 6.6%; cardiovascular events (myocardial infarction, stroke), 6%; solid malignancies (excluding basal cell carcinoma), 4.5%; chronic obstructive pulmonary disease, 3.5%. High intercountry variability was observed for both the prevalence of comorbidities and the proportion of subjects complying with recommendations for preventing and managing comorbidities. The systematic evaluation of comorbidities in this study detected abnormalities in vital signs, such as elevated blood pressure in 11.2%, and identified conditions that manifest as laboratory test abnormalities, such as hyperglycaemia in 3.3% and hyperlipidaemia in 8.3%. Conclusions Among RA patients, there is a high prevalence of comorbidities and their risk factors. In this multinational sample, variability among countries was wide, not only in prevalence but also in compliance with recommendations for preventing and managing these comorbidities. Systematic measurement of vital signs and laboratory testing detects otherwise unrecognised comorbid conditions.

Nonsteroidal anti-inflammatory drugs: adverse effects and their prevention.

OBJECTIVES To discuss nonsteroidal anti-inflammatory drugs (NSAIDs), their history, development, mode of action, toxicities, strategies for the prevention of toxicity, and future developments. METHODS Medline search for articles published up to 2007, using the keywords acetylsalicylic acid, aspirin, NSAIDs, cyclooxygenase 2, adverse effects, ulcer, and cardiovascular. RESULTS NSAIDs are 1 of the oldest, most successful drugs known to modern medicine. They are effective for alleviating pain, fever, and inflammation by inhibiting prostaglandin synthesis. Aspirin, by its irreversible inhibition of blood platelet function, is also effective in the prevention of cardiovascular disease. NSAIDs may cause gastrointestinal ulcers, serious cardiovascular events, hypertension, acute renal failure, and worsening of preexisting heart failure. These adverse effects may be prevented by limiting NSAID dosage and duration and by performing individual risk assessments and treating patients accordingly. Those at risk for gastroduodenal ulcers may be treated with concomitant proton-pump inhibitors, misoprostol and/or COX-2 selective NSAIDs. Those at risk for cardiovascular events may be treated with naproxen and a proton-pump inhibitor or misoprostol, but should best avoid NSAID use altogether. CONCLUSIONS Physicians should always prescribe the lowest effective dose for the shortest possible time and must take into account both the gastrointestinal and the cardiovascular risks of individual patients when prescribing NSAIDs.

Eradication of Helicobacter pylori Does Not Reduce the Incidence of Gastroduodenal Ulcers in Patients on Long-term NSAID Treatment: Double-Blind, Randomized, Placebo-Controlled Trial

Background:   Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are the major causes of gastroduodenal ulcers. Studies on the benefit of eradication of H. pylori in NSAID users yielded conflicting results.

Direct Medical Costs of Serious Gastrointestinal Ulcers among Users of NSAIDs

BackgroundThe occurrence and prevention of gastrointestinal ulcers during use of NSAIDs has become a major healthcare issue.ObjectiveTo determine the direct medical costs of serious NSAID-related ulcer complications.MethodAn observational cost-of-illness study was conducted in a large general hospital serving a population of 152 989 persons. From November 2001 to December 2003 all consecutive patients hospitalised with serious NSAID-related ulcer complications were identified. Serious NSAID-related ulcer complications were defined as ulcerations of the stomach or proximal duodenum causing perforation, obstruction or bleeding that occurred during the use of NSAIDs, necessitating hospitalisation of the patient. Data were retrieved with respect to days hospitalised and the number and type of diagnostic and therapeutic interventions. The main outcome measure was estimated mean direct medical costs of resources used.ResultsA total of 104 patients were hospitalised with serious NSAID-related ulcer complications (incidence 31.4 per 100 000 persons per year). Most patients were elderly (mean 70.4 years, SD 16.7). In-hospital mortality was 10.6%. Mean direct medical costs were €8375 (95% CI 7067, 10 393). On the basis of these results, we estimated that approximately 5105 people are hospitalised with serious NSAID-related ulcer complications in The Netherlands each year, of whom 541 die in hospital. The total annual direct medical costs for serious NSAID-related ulcer complications in The Netherlands were estimated to be €42 754 375 (95% CI 36 077 035, 53 056 265).ConclusionsSerious NSAID-related ulcer complications have a mortality rate of 10.6% in The Netherlands and the annual direct medical costs to the country of such complications are approximately €42 750 000.

Impact of patient-accessible electronic medical records in rheumatology: use, satisfaction and effects on empowerment among patients

BackgroundTo measure the use, satisfaction and impact of a web portal which provides patients with rheumatoid arthritis home access to their electronic medical records (EMR).MethodsA pretest-posttest study was conducted among 360 patients. Questionnaires assessed socio-demographics, health literacy, Internet use, disease characteristics, patient-provider relationship and empowerment before and after launching a hospital-based patient web portal. To measure the impact of the portal, patients’ satisfaction with care, trust in their rheumatologist, self-efficacy in patient-provider communication, illness perceptions, and medication adherence were assessed. The post-test included questions on portal use, satisfaction, and self-perceived impact due to portal use.Results54% of respondents with Internet access had viewed their EMR. Respondents were positive about the ease of use and usefulness of the portal and reported very few problems. Age (P = .03), amount of Internet use (P = .01) and self-perceived Internet skills (P = .03) significantly predicted portal use. Of the respondents who had logged in, 44% reported feeling more involved in their treatment and 37% felt they had more knowledge about their treatment. Significant differences over time were not found on the empowerment-related instruments.ConclusionsThe current portal succeeded in offering patients access to their EMR in a usable and understandable way. While its true impact is difficult to grasp, a relevant portion of the patients felt more involved in their treatment due to the web portal. Offering patients home EMR access, therefore, appears to be a valuable addition to the care process.

Statins inhibit the antirheumatic effects of rituximab in rheumatoid arthritis: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry

Rituximab (RTX) is used for the treatment of lymphomas and rheumatoid arthritis (RA), achieving its beneficial effect through B cell depletion.1 2 Recently it has been suggested that the effect of RTX may be inhibited by the concomitant use of statins.3,–,5 B cell depletion is achieved through apoptosis of B cells induced by hypercrosslinking of CD20 molecules with RTX. This process depends on the presence and integrity of lipid rafts in the cell membrane.3 6 7 In vitro, Winiarska et al showed that cholesterol depletion reduces apoptosis by RTX, inhibiting B cell depletion.3 However, two clinical studies that investigated concomitant statin use in patients with lymphoma reported no diminished effect on patient survival.8 9 These patients …

Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case-control study

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven. Selective cyclooxygenase-2 (COX-2) inhibitors reduce the risk for ulcer complications, but not completely in high-risk patients. This study determines which patients are especially at risk for NSAID ulcer complications and investigates the effectiveness of different preventive strategies in daily clinical practice. With the use of a nested case-control design, a large cohort of NSAID users was followed for 26 months. Cases were patients with NSAID ulcer complications necessitating hospitalisation; matched controls were selected from the remaining cohort of NSAID users who did not have NSAID ulcer complications. During the observational period, 104 incident cases were identified from a cohort of 51,903 NSAID users with 10,402 patient years of NSAID exposure (incidence 1% per year of NSAID use, age at diagnosis 70.4 ± 16.7 years (mean ± SD), 55.8% women), and 284 matched controls. Cases were characterised by serious, especially cardiovascular, co-morbidity. In-hospital mortality associated with NSAID ulcer complications was 10.6% (incidence 21.2 per 100,000 NSAID users). Concomitant proton-pump inhibitors (but not selective COX-2 inhibitors) were associated with a reduced risk for NSAID ulcer complications (the adjusted odds ratio 0.33; 95% confidence interval 0.17 to 0.67; p = 0.002). Especially at risk for NSAID ulcer complications are elderly patients with cardiovascular co-morbidity. Proton-pump inhibitors are associated with a reduced risk for NSAID ulcer complications.

Performance of the Dutch SF-36 version 2 as a measure of health-related quality of life in patients with rheumatoid arthritis

BackgroundThe aim of this study was to examine the measurement properties of the Dutch SF-36 version 2 (SF-36v2) health survey in patients with rheumatoid arthritis (RA).MethodsScaling assumptions, internal reliability, and internal construct validity were examined using available data from 1884 RA patients included in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. External construct validity and responsiveness to change were examined using baseline and 6-month follow-up data from a subset of 387 early RA patients participating in the DREAM remission induction cohort.ResultsThe individual items of the SF-36v2 adequately met scaling assumptions, although four items correlated too highly with items from different scales. Internal consistency was high for all eight scales and the physical and mental health components underlying the scales were replicated, supporting the use of the standard scoring algorithms. The SF-36v2 scales demonstrated minimal floor effects and ceiling effects were noteworthy only for the role-physical, social functioning, and role-emotional scales. Correlations with other core measures were as expected and the SF-36v2 showed excellent known-groups validity in distinguishing between patients with low or moderate-high disease activity. All scales related to physical health showed moderate to large responsiveness to change in patients that achieved low disease activity at six months.ConclusionThe SF-36v2 appears to be a psychometrically sound tool for the assessment of health-related quality of life of Dutch patients with RA.

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

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.

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.