Mortality in rheumatoid arthritis: have we made an impact in 4 decades?

OBJECTIVE: To evaluate trends in survival among patients with rheumatoid arthritis (RA) over the past 4 decades. METHODS: Three population based prevalence cohorts of all Rochester, Minnesota, residents age > or =35 years with RA (1987 American College of Rheumatology criteria) on January 1, 1965, January 1, 1975, and January 1, 1985; and an incidence cohort of all new cases of RA occurring in the same population between January 1, 1955 and January 1, 1985, were followed longitudinally through their entire medical records (including all inpatient and outpatient care by any provider) until death or migration from the county. Mortality was described using the Kaplan-Meier method and the influence of age, sex, rheumatoid factor (RF) positivity, and comorbidity (using the Charlson Comorbidity Index) on mortality was analyzed using Cox proportional hazards models. RESULTS: Mortality was statistically significantly worse than expected for each of the cohorts (overall p<0.0001). A trend toward increased mortality in the 1975 and 1985 prevalence cohorts compared to the 1965 prevalence cohort was present, even after adjusting for significant predictors of mortality (age, RF positivity, and comorbidity). Survival for the general population of Rochester residents of similar age and sex improved in 1975 compared to 1965, and in 1985 compared to 1975. CONCLUSION: The excess mortality associated with RA has not changed in 4 decades. Moreover, people with RA have not enjoyed the same improvements in survival experienced by their non-RA peers. More attention should be paid to mortality as an outcome measure in RA.     

Association of mortality with disease severity in rheumatoid arthritis, independent of comorbidity

OBJECTIVE: To measure the extent to which mortality in rheumatoid arthritis (RA) is associated with disease severity, independent of the presence of coexistent diseases (comorbidity). METHODS: We measured disease severity and comorbidity among RA patients attending scheduled appointments at a rheumatology clinic. We used the Duke Severity of Illness Checklist (DUSOI), a clinical judgment-based measure of the severity of disease. We disaggregated the DUSOI into an RA component (RADUSOI), which we used to measure RA disease severity, together with a physician-rated 10-point global RA severity assessment. We measured comorbidity using the non-RA component of the DUSOI (COMDUSOI) and using the Charlson Comorbidity Index. Patients were contacted periodically for up to 6 years, during which we recorded deaths. We estimated the effect of disease severity and comorbidity on mortality using Kaplan-Meier survival curves, Cox proportional hazards models, and logistic regression with receiver operating characteristics (ROC) curve analysis. RESULTS: The sample comprised 779 patients. Followup ranged from 0.1 year to 6.3 years (mean 2.52 years), for an observation period of 2,315 patient-years. Seventy-five patients died (9.6%), for a total mortality of 3.2 per 100 patient-years (95% confidence interval 2.6-4.1). Both disease severity and comorbidity displayed significant bivariate associations with mortality. In multivariate Cox models adjusted for age, sex, and disease duration, the RADUSOI and global RA severity scores were associated with mortality independent of either the COMDUSOI or Charlson Comorbidity scores. The area under the ROC curve for a logistic model on mortality increased from 0.79 with age, sex, and disease duration included, to 0.84 after adding RA severity and comorbidity (P < or = 0.005 for the increase in ROC area). CONCLUSION: RA disease severity is significantly associated with mortality regardless of the presence of comorbid disease. Combined with each patient's age, sex, and disease duration, information on RA severity and comorbidity allows an accurate prediction of mortality among patients with RA.     

Predictive validity of measures of comorbidity in older community dwellers: the Insufficienza Cardiaca negli Anziani Residenti a Dicomano Study

OBJECTIVES: To compare the ability of five measures of comorbidity to predict mortality and incident disability in basic activities of daily living (BADLs) in unselected older persons. DESIGN: An assessment of the data obtained from the Insufficienza Cardiaca negli Anziani Residenti a Dicomano (ICARe Dicomano) Study, a longitudinal epidemiological survey on heart failure in older people. SETTING: Dicomano, a small, rural town near Florence, Italy. PARTICIPANTS: The entire population aged 65 and older living in Dicomano, Italy, was enrolled in the ICARe Dicomano Study. MEASUREMENTS: At baseline (1995), comorbidity was quantified in 688 participants, based on clinical diagnoses, using disease count (DC), Charlson Comorbidity Index (CCI), Index of Co-Existent Diseases (ICED), and Geriatric Index of Comorbidity (GIC), or on drug use, using Chronic Disease Score (CDS). Incident ADL disability was assessed in 1999 and vital status in 2004. RESULTS: Mortality increased with the severity of comorbidity, with hazard ratios around 2 when comparing the highest and the lowest quartiles of DC, CCI, and ICED in Cox regressions adjusted for age, sex, and physical and cognitive performance. Prediction of mortality with GIC and CDS was only borderline significant. All measures predicted incident ADL disability; the strongest risk gradient (hazard ratio = 8.2 between the highest and lowest quartiles) was observed with ICED. Physical and, to a minor extent, cognitive performance added significantly to predicting mortality and incident BADL disability. CONCLUSION: All the measures of comorbidity predicted death and BADL disability in older community dwellers. DC, CCI, and ICED performed better than GIC and CDS. Physical performance measures are strong, independent contributors to the prediction of these outcomes.     

Comorbidity in patients with rheumatoid arthritis: effect on health-related quality of life

OBJECTIVE: To describe the extent of somatic comorbid conditions in patients with rheumatoid arthritis (RA) and to assess the influence of comorbidity on health-related quality of life (HRQOL). METHODS: A 2-year followup study on health and HRQOL was conducted among 679 patients with RA with varying disease duration. Data were collected by means of questionnaires and clinical examinations at baseline and at 2-year followup. Comorbidity was measured by a self-administered questionnaire including 17 chronic diseases. HRQOL was assessed with the RAND-36. The effect of incident comorbid conditions on HRQOL was investigated with linear regression analyses. RESULTS: At least one comorbid condition was reported at baseline by 56% of patients. Significant differences in prevalence rates with the Dutch population were found. The effect of comorbidity on HRQOL depended on both the type of comorbid condition and the dimension of HRQOL. Gastrointestinal (GI) diseases, cancer, dizziness with falling (and less severe chronic pulmonary disease and heart complaints) resulted in significant adverse changes in HRQOL. For the other conditions under study no influence could be detected. CONCLUSION: Our results indicate that measuring comorbidity by a summary count, assuming an overall equally large effect of each comorbid condition, may not reveal the real effect. With respect to clinical practice, our results emphasize the relevance for health care providers to be aware of specific comorbid conditions exposing patients with RA at risk for additional impairment of HRQOL, and to be aware of interactions with RA that may be unique.     

All-cause mortality and vascular events among patients with rheumatoid arthritis,osteoarthritis, or no arthritis in the UK General Practice Research Database

OBJECTIVE: To compare all-cause mortality rates and the incidence of major vascular events among patients with rheumatoid arthritis (RA), osteoarthritis (OA) without RA, or no arthritis using the UK General Practice Research Database (GPRD) while adjusting for age and sex. Clinic-based studies have found that patients with RA have higher all-cause and cardiovascular (CV) mortality than those without RA, after adjusting for age and sex. Much smaller elevations in risk have been found in the few community-based studies that have addressed this question. METHODS: After excluding patients with a history of myocardial infarction or cerebrovascular events, we followed a retrospective cohort of patients 40 years and older from GPRD practices until the earliest of death, disenrollment, or the occurrence of an incident vascular event. Using Poisson regression we compared age and gender adjusted incidence rates for RA, OA, or no arthritis. RESULTS: Five hundred and ninety-four practices contributed 2.37 million patients (1.11 million men and 1.26 million women) to the analysis. Over a mean duration of followup of almost 5 years, age and gender adjusted all-cause mortality rates were 60 to 70% higher in patients with RA compared to patients with OA and those with no arthritis. For the various vascular endpoints, the age and gender adjusted incidence rates were 30 to 60% higher in patients with RA compared to both patients with OA and those with no arthritis during the study period. The rates in patients with OA and those with no arthritis were essentially the same. CONCLUSION: Compared to patients with OA and those with no arthritis, patients with RA had a higher age and gender adjusted incidence of all-cause mortality and of major vascular events during almost 5 years of followup.     

Clinical comorbidity in patients with osteoarthritis: a case-control study of general practice consulters in England and Wales

OBJECTIVES: To determine patterns of clinical comorbidity in general practice consulters with OA and compare them with comorbidity in consulters without OA. METHODS: A case-control study nested in a one-year prevalence survey of consultations in 60 general practices in England and Wales. Cases were 11 375 subjects aged 50 and over who had consulted with OA during the study year. Controls were 11 780 subjects matched for age and sex who had consulted during the study year, but not for OA. Morbidity outcomes were based on a standard clinical classification system. RESULTS: After adjusting for age, sex, and social class, cases were significantly more likely to have high levels of comorbidity than controls (2.35; 2.16 to 2.55). Significant OA comorbid associations with other musculoskeletal conditions included arthropathies (OR 2.26; 99% CI 1.50 to 3.41), upper limb sprain (2.04; 1.38 to 3.00), synovial and tendon disorders (2.03; 1.54 to 2.68), and other joint disorders (2.00; 1.71 to 2.32). OA non-musculoskeletal associations were with obesity (2.25; 1.73 to 2.92), gastritis (1.98; 1.46 to 2.68), phlebitis (1.80; 1.28 to 2.52), diaphragmatic hernia (1.80; 1.29 to 2.51), ischaemic heart disease (1.73; 1.13 to 2.66) and intestinal diverticula (1.63; 1.20 to 2.23). CONCLUSIONS: Comorbidity for OA was extensive, with musculoskeletal as well as non-musculoskeletal conditions. Age, sex, and social class did not explain this comorbidity but propensity to consult may be a part explanation. An important question remains as to whether comorbidity in general practice significantly adds to the disability or further impairs the health of patients with OA.     

Baseline comorbidities in patients with rheumatoid arthritis who have been prescribed biological therapy: A case control study

AimTo determine whether rheumatoid arthritis (RA) patients who have been prescribed biological agents exhibit a different comorbidity burden than RA patients who take disease-modifying antirheumatic drugs (DMARDs) alone, and to understand the association between comorbidity and other variables, as well as the association between comorbidity and multimorbidity.MethodsThis observational case–control study included 114 RA patients treated with biological agents and a control group comprising 163 sex- and age-matched RA patients treated with DMARDs only. Current and previous data regarding the patients’ disease activity, comorbidities, and treatments were collected. The data were analysed using bivariate and multivariate regression models.ResultsThe patients who were prescribed biological agents exhibited poorer disease control, received more DMARDs and steroids, and underwent more total joint arthroplasties compared with the patients in the control group. However, the risk factors for cardiovascular disease and the comorbidity frequency were similar between cases and controls. The most prevalent comorbidities were hypertension, obesity, and respiratory, thyroid, and upper gastrointestinal disorders. The incidence of cardiovascular disease was low, and only 29% of the patients exhibited multimorbidities. A bivariate association of age, late diagnosis, joint replacements and a high score on the health assessment questionnaire score (HAQ) with comorbidity was observed. There were also correlations between the Charlson index and age, joint reconstructive surgery, disease activity (DAS28), and HAQ score. However, when binary logarithmic regression models were applied, only patient age remained significantly associated with comorbidity and multimorbidity [hazard ratio, 1.08; 95% confidence interval, 1.05–1.12; p < 0.0005].ConclusionRA patients taking biological drugs have a comorbidity burden equivalent to those treated with DMARDs alone. Age is the main predictive factor of comorbidity in these patients.     

Performance of comorbidity indices in measuring outcomes after acute myocardial infarction in Australian indigenous and non-indigenous patients

Background: Indigenous Australians have higher prevalence of chronic diseases and worse acute care outcomes than other Australians. The extent to which higher chronic disease comorbidity levels are responsible for their worse outcomes is not clear, and the performance of comorbidity indices has not been assessed for this population with very high comorbidity levels. Methods: Using hospital separations data, the Charlson and Elixhauser comorbidity indices were used to measure chronic disease prevalence in 2035 indigenous and non‐indigenous patients hospitalised after their first acute myocardial infarction (AMI) in the Northern Territory of Australia between 1992 and 2004, and to adjust for comorbidity in multivariate analysis of mortality outcomes (in‐hospital and long‐term deaths from coronary heart disease and all causes). Index performance was assessed by the difference between C statistic, Akaike information criterion statistic and estimate of excess indigenous mortality in models with and without comorbidity adjustment. Results: Comorbidity index scores were higher for indigenous than non‐indigenous patients and increased considerably over time, at least partly because of information bias. Indigenous patients' higher risk of in‐hospital all‐cause death was almost fully explained by their higher comorbidity levels. Their higher risk of long‐term coronary heart disease and all‐cause death was partially explained by higher comorbidity levels. Charlson and Elixhauser indices performed satisfactorily and similarly in this population. Conclusion: Comorbidity indices performed well in a population with very high chronic disease prevalence. After adjusting for comorbidity, short‐term outcomes were similar for indigenous and non‐indigenous AMI patients, but comorbidity at the time of the acute episode only partly explained the worse long‐term outcomes for indigenous patients.     

Health-related quality of life in women with symptomatic hand osteoarthritis: a comparison with rheumatoid arthritis patients, healthy controls, and normative data

OBJECTIVE: Data on the burden of disease and impact on health-related quality of life (HRQOL) in hand osteoarthritis (OA) are limited. The goal of this study was to compare HRQOL in patients with hand OA with HRQOL in patients with rheumatoid arthritis (RA), healthy controls, and normative data from the general population. METHODS: A total of 190 women with hand OA were compared with 194 women with RA and 144 healthy women of the same age. Health status was measured using the Short Form 36 (SF-36), Short Form 6D (SF-6D), modified Health Assessment Questionnaire (M-HAQ), pain and fatigue visual analog scales, and grip strength. Scores were compared by analysis of variance and a multivariate analysis of covariance, adjusting for age, number of comorbidities, and years of education. Gaps between patients and population subjects were assessed by calculating S scores on all dimensions of the SF-36. RESULTS: Hand OA and RA patients had worse scores on all assessed dimensions of subjective health compared with healthy controls. RA patients showed poorest general health (SF-36), poorest physical function (M-HAQ, SF-36 physical, grip strength), and highest level of fatigue compared with hand OA patients. Hand OA patients reported poorer mental health. Mean utility scores (SF-6D) in hand OA and RA were 0.64 and 0.63, respectively, with a mean difference compared with healthy controls of 0.13 in hand OA and 0.14 in RA patients. S scores confirmed a marked disparity between individuals with a rheumatic diagnosis (hand OA, RA) and population subjects. CONCLUSION: This study illustrates that patients with hand OA experience a broad impact on HRQOL compared with healthy controls. Fatigue and physical function are worse in RA than hand OA.     

Hypothyroidism risk associated with rheumatoid arthritis: A population-based retrospective cohort study

Studies on the thyroid disease risk in patients with rheumatoid arthritis (RA) associated with comorbidities are limited. This population-based retrospective cohort study investigated the hypothyroidism risk in patients with RA and the role of comorbidities.We used Taiwan National Health Insurance Research Database to identify 16,714 RA patients newly diagnosed in 2000 to 2008 and 66,856 control persons without RA, frequency matched by sex, age, and index year. Incidence and the RA group to controls hazard ratio of hypothyroidism were estimated.The hypothyroidism incidence was 1.74-fold higher in the RA group than in controls (16.6 vs 9.52 per 10,000 person–years), with the Cox method estimated adjusted hazard ratio of 1.67 (95% confidence interval = 1.39–2.00) after controlling for covariates. Near 75% of the study population were women, with the incidence 3.6-time higher than men in both groups. The hypothyroidism incidence increased with age, from 12.1 per 1000 person–years in 20 to 39 years to 20.0 per 1000 person–years in 60+ years in RA patients, higher than that in controls (7.17 vs 10.0 per 1000 person–years, respectively by age). Each comorbidity was related to an increased incidence and higher in the RA group than in controls. Among all comorbidities, stroke exerted the greatest impact in the RA group with an adjusted hazard ratio of 3.85 (95% confidence interval = 1.24–12.0).RA patients have an increased risk of developing hypothyroidism; this risk was pronounced in women and the elderly. RA patients should be closely monitored to prevent the development of hypothyroidism.     

Excess mortality emerges after 10 years in an inception cohort of early rheumatoid arthritis

Objective

To investigate mortality rates, causes of death, time trends in mortality, prognostic factors for mortality, and the relationship between disease activity and mortality over a 23‐year period in an inception cohort of rheumatoid arthritis (RA) patients.

Methods

A prospective inception cohort of RA patients diagnosed between January 1985 and October 2007 was followed for up to 23 years after diagnosis. Excess mortality was analyzed by comparing the observed mortality in the RA cohort with the expected mortality based on the general population of The Netherlands, matched for age, sex, and calendar year. Period analysis was used to examine time trends in survival across calendar time. Prognostic factors for mortality and the influence of the time‐varying Disease Activity Score in 28 joints (DAS28) on mortality were analyzed using multivariable Cox proportional hazards models. Causes of death were analyzed.

Results

Of the 1,049 patients in the cohort, 207 patients died. Differences in observed and expected mortality emerged after 10 years of followup. No improvement in survival was noted over calendar time. Significant baseline predictors of survival were sex, age, rheumatoid factor, disability, and comorbidity. Higher levels of DAS28 over time, adjusted for age, were associated with lower survival rates, more so in men (hazard ratio [HR] 1.58, 95% confidence interval [95% CI] 1.35–1.85) than in women (HR 1.21, 95% CI 1.04–1.42).

Conclusion

Excess mortality in RA emerged after 10 years of disease duration. Absolute survival rates have not improved in the last 23 years and a trend toward a widening mortality gap between RA patients and the general population was visible. Higher disease activity levels contribute to premature death in RA patients.     

Comorbidity in rheumatoid arthritis of early onset. Effects on outcome parameters

Three-year follow-up data of 1,032 patients with recent onset rheumatoid arthritis (RA) were analyzed regarding the frequency of 21 common comorbid chronic conditions and their impact on health outcome (i.e., pain, functional capacity, disease activity, and radiographic joint damage). Multivariate logistic regression analyses were used to calculate age- and gender-adjusted odds ratios for each chronic condition on severe functional capacity (<60% of full function). Comorbidity was already common at the onset of RA, with 72% of the patients having at least one comorbid condition and almost 50% having at least two. Common comorbidities were associated with significantly worse baseline measures in at least three of seven investigated outcome parameters. The more of these conditions patients had, the worse their 3-year outcome. Functional capacity was most sensitive to comorbid conditions. In logistic regression, obesity, hypercholesterolemia, type II diabetes, and osteoporosis resulted in a twofold risk of severe functional limitation (<60% of full function), independent of each other and of age and gender. The impact of comorbidity on measures of disease severity should be considered when used to compare outcome parameters of different RA samples.     

Prevalence and comorbidities of chronic hepatitis C: a nationwide population-based register study in Sweden

Purpose: The aim of this study was to estimate the prevalence of physician-diagnosed and registered chronic hepatitis C (CHC), and to estimate the reported frequencies of Charlson comorbidities compared with matched comparators from the general population.

Materials and methods: Patients were identified according to ICD codes for CHC in the Swedish National Patient Register (1997–2013). Prevalence was estimated according to different patient identification algorithms and for different subgroups. Charlson comorbidities were ascertained from the same register and compared with age/sex/county of residence matched general population comparators.

Results: A total of 34,633 individuals with physician-diagnosed CHC were alive in Sweden in 2013 (mean age, 49 years; 64% men), corresponding to a physician-diagnosed prevalence of 0.36%. The prevalence varied by case definition (0.22%-0.36%). The estimate dropped to 0.14% for monitored CHC disease (defined as ≥1 CHC-related visit in 2013). Overall, 41.3% of the CHC patients had ≥1 physician-registered Charlson comorbidity; the most common was liver diseases (22.1%). Compared with matched comparators from the general population (n?=?171,338), patients with CHC had more physician-diagnosed and registered diseases such as chronic pulmonary disease (10.2% vs. 4.0%), diabetes (10.6% vs. 5.5%) and liver-related cancer (1.3% vs. 0.2%; all p?<?.01). No information on behavioural factors, such as smoking, alcohol consumption or on-going illicit drug use, was available.

Conclusion: The physician-diagnosed prevalence of CHC was slightly lower than previously reported estimates, and varied by case definition. The additional comorbidities observed in the CHC group should be taken into consideration, as these comorbidities add to the disease burden.     

Clinical comorbidity in osteoarthritis: associations with physical function in older patients in family practice

OBJECTIVE: To determine the influence of comorbidity on physical function in osteoarthritis (OA) consulters aged 50 years and over in family practice. METHODS: The study design linked morbidity consultations during an 18-month period to self-reported physical function status measured at the end of the period. Clinical comorbidity was compared between consulters with (n = 1026) and without (n = 8160) OA. Comorbidity was defined by morbidity counts (1-2 low, 3-4 medium,> 5 high) and by a measure of severity of individual morbidities based on chronicity. Associations between comorbidity and physical function were assessed using unconditional logistic regression, adjusting for age, sex, and socioeconomic deprivation. RESULTS: Of the 1026 OA consulters, 38 (3.7%) had an OA consultation only, 260 (25.3%) had low, 288 (28.1%) medium, and 440 (42.9%) high morbidity counts. Higher OA comorbid counts were associated with poorer physical function, after adjusting for age, sex, and socioeconomic deprivation. Associations between OA comorbidity severity and poor physical function showed estimates that were in excess of simply multiplying the individual effects of OA and comorbidity severity separately. Comorbidity, however, did not explain all of the association between OA and poor physical function. CONCLUSION: Comorbidity increases the likelihood of poor physical function in patients with OA in population-based family practice. The combined influence is greater than would be expected from the influence of either OA or the comorbid conditions alone. Treating comorbidity in patients with OA is likely to be crucial in preventing or reducing the related physical decline.     

Komorbidität bei früher rheumatoider Arthritis

Three-year follow-up data of 1,032 patients with recent onset rheumatoid arthritis (RA) were analyzed regarding the frequency of 21 common comorbid chronic conditions and their impact on health outcome (i.e., pain, functional capacity, disease activity, and radiographic joint damage). Multivariate logistic regression analyses were used to calculate age- and gender-adjusted odds ratios for each chronic condition on severe functional capacity (<60% of full function). Comorbidity was already common at the onset of RA, with 72% of the patients having at least one comorbid condition and almost 50% having at least two. Common comorbidities were associated with significantly worse baseline measures in at least three of seven investigated outcome parameters. The more of these conditions patients had, the worse their 3-year outcome. Functional capacity was most sensitive to comorbid conditions. In logistic regression, obesity, hypercholesterolemia, type II diabetes, and osteoporosis resulted in a twofold risk of severe functional limitation (<60% of full function), independent of each other and of age and gender. The impact of comorbidity on measures of disease severity should be considered when used to compare outcome parameters of different RA samples.     

Influenza and pneumococcal vaccination in patients with rheumatoid arthritis in comparison with age- and sex-matched controls: results of a claims data analysis

The aim of this study was to assess the vaccination status for influenza and pneumonia and the prevalence of hospitalised pneumonia in rheumatoid arthritis (RA) patients and population controls in Germany. Members of a large statutory health insurance fund in Germany who were continuously insured between 2009 and 2013 and had a diagnosis of RA in 2013 were age and sex matched 1:5 to members without RA. Pneumococcal and influenza vaccinations were evaluated with regard to age, sex and region of residence. Logistic regression models were used to determine predictors for influenza vaccination in RA patients. Prevalences of pneumonia that required hospitalisation were compared to regional vaccination rates. The data of 111,482 RA patients and 557,410 matched controls were available for analysis. Compared to controls, RA patients were vaccinated more frequently against influenza (40.8 vs. 32.2 %) and pneumonia (15.0 vs. 10.0 %). Vaccination rates increased with older age and differed between the federal states (highest in East Germany, lowest in South Germany). The region of residence, comorbidities, rheumatologic care and biologic treatment was associated with a higher probability of an influenza vaccination. Prevalences of pneumonia that required hospitalisation were 2–3 times higher in patients compared to controls and tended to be higher in regions with low vaccination rates. The increased pneumonia prevalence in RA patients confirms their status as a risk group. RA patients are vaccinated more frequently than controls, but vaccination rates are still low. The lower pneumonia prevalence in East Germany indicates that vaccination may help to reduce pneumonia in RA.     

Telopeptides as markers of bone turnover in rheumatoid arthritis and osteoarthritis

AIMS: The aim of the present study was to determine if urinary excretion of type I collagen N-terminal telopeptides (UrNTx) and deoxypyridinoline (UrDPD) and serum levels of type I collagen C-terminal telopeptides (SeCTx) differed in patients with rheumatoid arthritis (RA) compared with populations matched for age and gender with and without osteoarthritis (OA). The correlation of markers of bone turnover with disease activity in patients with RA or radiographic severity in patients with OA was also examined. METHODS: Patients with RA aged >50 years (men) and >60 years (women) were identified from computer databases at two tertiary referral centres for rheumatology. Strict exclusion criteria were applied to avoid the effects of factors known to influence markers of bone turnover. Patients with RA and OA were matched for age and sex with a control population free of known arthritic disease and a population with OA. Bone markers were assayed in serum and urine. Urine markers were measured on three consecutive days and mean values used to minimize day-to-day variability of these analytes. RESULTS: The level of UrNTx was elevated in patients with RA compared with normal controls and patients with OA. UrNTx and UrDPD correlated with markers of disease activity in patients with RA (erythrocyte -sedimentation rate and C-reactive protein), but not with -clinical signs of inflammation (swollen and tender joint counts). Patients with OA failed to show any correlation between markers of bone turnover and radiographic severity. CONCLUSIONS: These data support a role for the use of UrNTx and UrDPD in further studies of the patho-physiology of RA and in longitudinal studies designed to modify the course of clinical disease.     

Baseline comorbidity levels in biologic and standard DMARD treated patients with rheumatoid arthritis: results from a national patient register

OBJECTIVE: To describe the occurrence of baseline comorbidity in subjects with active rheumatoid arthritis starting treatment with biological agents. Such data are necessary to interpret the reported occurrence of adverse events following treatment. METHODS: Baseline comorbidity was recorded in a large national cohort of patients with rheumatoid arthritis newly starting biological agents. The distribution of the number and types of comorbidities is presented. RESULTS: In all, 7818 patients treated with biological agents (infliximab 3332, etanercept 3302, adalimumab 1059, anakinra 132) were included in the analysis. Comorbidity was common, with 58% of patients having at least one comorbid condition and 25% having more than one. The most frequent comorbid conditions were hypertension, depression, peptic ulcer disease, and respiratory disease. CONCLUSIONS: In routine use, patients treated with biological agents have high levels of baseline comorbidity, which should influence the interpretation of reported adverse events.     

Occurrence of extraarticular disease manifestations is associated with excess mortality in a community based cohort of patients with rheumatoid arthritis

OBJECTIVE: To investigate the occurrence of extraarticular manifestations (ExRA) in a well defined community based cohort of patients with rheumatoid arthritis (RA), and to examine their effect on mortality. METHODS: Using the resources of the Rochester Epidemiology Project, a retrospective medical record review was conducted of a cohort of 424 cases of RA in Olmsted County, MN, USA, diagnosed during the period 1955-1985. These cases had been classified using the American College of Rheumatology 1987 criteria for RA. Patients were followed 1955-1998 (median followup 14.8 yrs; range 0.2-42.8 yrs), and incident ExRA manifestations were recorded according to predefined criteria. Data on comorbidities were extracted using the definitions of the Charlson comorbidity index. Survival was compared to the general population using Kaplan-Meier estimates. RESULTS: ExRA occurred in 169 patients, corresponding to an incidence rate of 3.67/100 person-yrs. Compared to the general population, survival among patients with RA was decreased. Survival among patients with ExRA was markedly decreased compared to the general population and to patients without ExRA (p < 0.001). A particularly poor prognosis was noted in a subgroup of 63 patients (incidence rate 1.04/100 person-yrs) who fulfilled predefined criteria for severe ExRA (i.e., vasculitis, pericarditis, pleuritis, and/or Felty's syndrome). For RA patients who did not fulfill these criteria, there was no significant increase of mortality (p = 0.09). In a multivariate model of mortality, including age, sex, and the presence of known comorbidities, the presence of one or more of these ExRA was the strongest predictor of mortality. CONCLUSION: In this first community based study of extraarticular manifestations in RA, virtually all the excess mortality occurred in a subgroup of patients with severe extraarticular disease, suggesting that extraarticular disease is the major predictor of mortality in patients with RA.