Rheumatoid Arthritis: Leufkens HG

van Staa TP, Geusens P, Bijlsma JW, Leufkens HG, Cooper C. · MRC Epidemiology Resource Centre, University of Southampton, Southampton, UK. · Arthritis Rheum. · Pubmed #17009229 links to  free full text

Abstract: OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) have an increased risk of fracture, and to estimate their long-term absolute fracture risk. METHODS: We studied patients with RA ages >or=40 years in the British General Practice Research Database, each matched by age, sex, calendar time, and practice to 3 control patients. Incident fractures, as recorded in the computerized medical records, were ascertained over a median followup of 7.6 years. The fracture rate in RA patients compared with controls was adjusted for smoking, body mass index (BMI), and several clinical risk factors, and Cox proportional hazards models were used to calculate the relative risk (RR) of fracture in RA. A risk score was then developed to provide an estimate of the 5- and 10-year fracture risk among RA patients. RESULTS: There were 30,262 patients with RA, of whom 2,460 experienced a fracture during followup. Compared with controls, patients with RA had an increased risk of fracture, which was most marked at the hip (RR 2.0, 95% confidence interval [95% CI] 1.8-2.3) and spine (RR 2.4, 95% CI 2.0-2.8). Indicators of a substantially elevated risk of fracture (at the hip) included >10 years' duration of RA (RR 3.4, 95% CI 3.0-3.9), low BMI (RR 3.9, 95% CI 3.1-4.9), and use of oral glucocorticoids (RR 3.4, 95% CI 3.0-4.0). Modeling of the long-term risk profiles revealed that, for example, in a woman age 65 years with longstanding RA whose risk factors also included low BMI, a history of fracture, and frequent use of oral glucocorticoids, the 5-year risk of hip fracture was 5.7% (95% CI 5.3-6.1%). CONCLUSION: Patients with RA are at increased risk of osteoporotic fractures. This increased risk is attributable to a combination of disease activity and use of oral glucocorticoids.

van Staa TP, Geusens P, Zhang B, Leufkens HG, Boonen A, Cooper C. · Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. · Rheumatology (Oxford). · Pubmed #16899499 links to  free full text

Abstract: OBJECTIVES: There are few data on the cost-effectiveness of bisphosphonates with oral glucocorticoids (GCs). An individual patient-based pharmaco-economic model was developed. METHODS: Data were obtained from a cohort of oral GC users aged 40+ (n = 190 000) in the UK General Practice Research Database. Individualized fracture and mortality risks were calculated specific for age, sex, daily and cumulative GC dose, indication and other clinical risk factors. UK costs of medication and direct costs of fracture were obtained from National Institute for Clinical Excellence and used to estimate costs per quality-adjusted life-year (QALY) gained and fracture prevented for bisphosphonates in patients treated for 5 yrs with GCs. RESULTS: With the use of 5 mg GCs daily, the cost per one QALY gained with bisphosphonates was 41k UK pounds (95% confidence intervals 22-72k) in women aged <60 [men 40k pounds (29-54k)], 17k pounds (13-24k) in women aged 60-79 [men 43k pounds (31-60k)], 5k pounds(3-6k) in women aged 80+ [men 35k pounds (25-46k)]. With 15 mg GC, these figures were 17k pounds (14-21k), 13k pounds (10-16k) and 15k pounds (9-26k) in women and 22k pounds (17-26k), 34 pounds (23-53k) and 33k pounds (27-42k) in men, respectively. When stratifying by overall fracture risk and life expectancy at the start of GC therapy, cost per QALY increased with decreasing life expectancy. Patients with rheumatoid arthritis had comparatively better cost-effectiveness, given higher fracture risk and better life expectancy. CONCLUSIONS: The cost-effectiveness of bisphosphonates varied substantially. Bisphosphonates can be considered cost-effective in patients with higher fracture risks, such as elderly patients (with a life expectancy over 5 yrs), and younger patients with a fracture history, low body mass index, rheumatoid arthritis or using high GC doses.

Florentinus SR, Heerdink ER, de Boer A, van Dijk L, Leufkens HG. · Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht University, Faculty of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht, The Netherlands. · Pharmacoepidemiol Drug Saf. · Pubmed #15937867 No free full text.

Abstract: BACKGROUND: The cyclooxygenase-2 (COX-2) inhibitor rofecoxib was registered in 1999. By 2000, the first reports were published indicating that the agent was possibly associated with an increased risk of myocardial infarction. Since then a surge of data supporting this association has become available. To interpret these data it is essential to ascertain the cardiovascular risk profile of users of rofecoxib relative to other non-steroidal anti-inflammatory drug (NSAID) recipients. OBJECTIVE: To assess differences in cardiovascular risk between starters of rofecoxib versus starters of any other NSAID. SETTING: Data sampled from a representative research network of Dutch general practitioners (GPs) in 2001. DESIGN: New users (starters) of rofecoxib were compared to starters of any other NSAID, unmatched and matched on age, gender, and indication nested in the cohort of the second Dutch National Survey of General Practice. RESULTS: A total of 40.4% of patients starting on rofecoxib had cardiovascular co-morbidity. Patients starting on rofecoxib were twice more likely to have a history of gastrointestinal (GI) morbidity, compared to patients starting on other NSAIDs (OR(adj) = 2.09; 95%CI = 1.65-2.66). These patients were also more likely to have cardiovascular co-morbidity (OR = 1.90; 95%CI = 1.60-2.24) compared to recipients of rofecoxib with no GI co-morbidity. Cardiovascular morbidity was present at the time of rofecoxib exposure in over 61% of carriers of a composite risk profile including age 60 years or older, GI co-morbidity and diagnosis of rheumatoid arthritis and osteoarthritis. CONCLUSIONS: In general, a typical recipient of an NSAID is aged and carrier of a serious cardiovascular risk profile. Selective prescribing of rofecoxib to provide claimed gastroprotection, indirectly and unintentionally resulted in prescribing rofecoxib in a population with high frequencies of cardiovascular morbidities.

Souverein PC, Berard A, Van Staa TP, Cooper C, Egberts AC, Leufkens HG, Walker BR. · Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, PO Box 80082, 3508 TB Utrecht, The Netherlands. · Heart. · Pubmed #15253953 links to  free full text

Abstract: OBJECTIVE: To assess whether use of oral glucocorticoids is associated with cardiovascular and cerebrovascular morbidity. DESIGN AND SETTING: Nested case-control study within a cohort of patients (> or = 50 years old) with at least one prescription for oral or non-systemic glucocorticoids. Data were from the general practice research database. PATIENTS: 50 656 patients were identified with a first record for ischaemic heart disease (International classification of diseases, ninth revision (ICD-9) codes 410, 411, 413, and 414), ischaemic stroke or transient ischaemic attack (ICD-9 codes 430-436), or heart failure (ICD-9 code 428) between 1988 and 1998. One control was matched to each case by sex, age, general practice, underlying disease, and calendar time. MAIN OUTCOME MEASURE: Odds ratio (OR) of cardiovascular or cerebrovascular events in patients using oral glucocorticoids compared with non-users. RESULTS: There was a significant association between ever use of oral glucocorticoids and any cardiovascular or cerebrovascular outcome (adjusted OR 1.25, 95% confidence interval (CI) 1.21 to 1.29). The association was stronger for current use of oral glucocorticoids than for recent or past use. Among current users, the highest ORs were observed in the group with the highest average daily dose, although the dose-response relation was not continuous. Current use was associated with an increased risk of heart failure (adjusted OR 2.66, 95% CI 2.46 to 2.87), which was consistent between patients with rheumatoid arthritis, patients with chronic obstructive pulmonary disease, and patients without either of the two conditions. Also, current use was associated with a smaller increased risk of ischaemic heart disease (OR 1.20, 95% CI 1.11 to 1.29). CONCLUSIONS: Oral glucocorticoid use was identified as a risk factor for heart failure. However, the evidence remains observational and only a randomised controlled trial of glucocorticoid treatment versus other disease modifying agents is likely to distinguish the importance of the underlying disease activity from its treatment in predicting cardiovascular outcomes.