Immunogenicity of subcutaneous TNF inhibitors and its clinical significance in real-life setting in patients with spondyloarthritis.

KEY MESSAGES: Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1-2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients.

Three out of four disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients meet 28-joint Disease Activity Score remission at 12 months: results from the FIN-ERA cohort.

OBJECTIVE: To assess what proportion of patients with disease-modifying anti-rheumatic drug (DMARD)-naïve early rheumatoid arthritis (ERA) reach 28-joint Disease Activity Score (DAS28) remission over 1 year, and remission variability across clinics in Finland. METHOD: Patients with DMARD-naïve newly diagnosed inflammatory arthritis were recruited. The proportion of patients in 28-joint Disease Activity Score with three variables (DAS28-3) remission was compared across sites. Repeated measures were analysed using a mixed models approach with appropriate distribution and link function. RESULTS: In total, 611 patients were recruited at five sites: 67% were female; the mean (sd) age was 57 (16) years; 71% and 68% were positive for rheumatoid factor and anti-cyclic citrullinated peptides, respectively; and 23% had radiographic erosions. A total of 506 (83%) fulfilled the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for rheumatoid arthritis for further analyses. DAS28-3 remission was met by 68% and 75% at 3 and 12 months, respectively. The clinical site had no effect on remission when adjusted for confounders. At baseline, 68% used methotrexate-based combination therapy, and 31% used triple therapy with methotrexate, hydroxychloroquine, and sulphasalazine (the Fin-RACo regimen). In multivariate analysis, the only independent predictors of DAS28-3 remission at 12 months were lower baseline DAS28-3 and triple therapy as the initial treatment. CONCLUSION: Three out of four DMARD-naïve ERA patients in Finland are in remission during the first year from the diagnosis. High remission rates were achieved for most patients with the use of conventional synthetic DMARDs in combination. Treatment of DMARD-naïve ERA patients with the FIN-RACo regimen is a predictor of DAS28-3 remission in real-life rheumatology settings.

Drug survival on tumour necrosis factor inhibitors in patients with rheumatoid arthritis in Finland.

OBJECTIVE: A systematic review found that an average of 27% of rheumatoid arthritis (RA) patients using tumour necrosis factor (TNF) inhibitors discontinue their treatment within 1 year. The aim of this study was to assess drug survival on TNF inhibitors among patients with RA. METHODS: Patients were identified from the National Register for Biologic Treatment in Finland (ROB-FIN), which is a longitudinal cohort study established to monitor the effectiveness and safety of biologic drugs in rheumatic diseases. Inclusion was limited to TNF-inhibitor treatments started as the patient's first, second, or third biologic treatment between 2004 and 2014. Follow-up was truncated at 36 months. The results of a time-dependent Cox proportional hazards model were reported as adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Of the 4200 TNF-inhibitor treatment periods identified from ROB-FIN, 3443 periods from 2687 patients met the inclusion criteria. Twenty-seven per cent of the patients discontinued their treatment within 12 months. Infliximab (HR 1.8, 95% CI 1.3-2.5) and certolizumab pegol (HR 1.7, 95% CI 1.2-2.3) had lower drug survival compared to golimumab. A similar trend was seen with adalimumab (HR 1.2, 95% CI 0.90-1.7) and etanercept (HR 1.2, 95% CI 0.87-1.6). Concomitant use of methotrexate (MTX) was associated with improved drug survival (HR 0.76, 95% CI 0.64-0.90) in comparison with TNF-inhibitor monotherapy. CONCLUSIONS: Golimumab was better in terms of drug survival than infliximab or certolizumab pegol and at least as good as adalimumab and etanercept. Concomitant use of MTX improved drug survival on TNF inhibitors.

A nationwide cross-sectional overview of patients with rheumatoid arthritis followed in outpatient specialty clinics in Finland.

OBJECTIVES: We aimed to conduct a cross-sectional overview of patients with rheumatoid arthritis (RA) in outpatient specialized clinics in Finland. METHOD: Consecutive patients were enrolled in the study. The data collected comprised demographic, disease- and treatment-related variables. RESULTS: Between November 2011 and May 2012, 890 patients with RA (77% female) were enrolled from 14 sites. The median age was 59.8 years and the time from diagnosis 7.2 years. Values for the Disease Activity Score using 28 joint counts (DAS28) ranged from 0.28 to 6.61 (median 2.55) with 52% and 70% of patients reaching remission and low disease activity, respectively. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies were evident in 70% and 63% of patients, respectively. Median Health Assessment Questionnaire (HAQ) scores with and without aids and devices were 0.75 [interquartile range (IQR) 0.13-1.38] and 0.63 (IQR 0.13-1.13), respectively. Conventional disease-modifying anti-rheumatic drugs (DMARDs) were used by 91% of patients. A triple therapy of methotrexate (MTX), hydroxychloroquine (HCQ), and sulfasalazine (SSZ) was used by 15%, other MTX-based combination by 30%, MTX alone by 20%, and other DMARDs alone or in combination by 26% of patients. In addition, glucocorticoids and biologics were taken by 58% and 21% of patients, respectively. Of the 184 biologics users, 18% were not using DMARDs concomitantly. CONCLUSIONS: Our cross-sectional review of patients with RA revealed that > 50% of patients were in remission according to DAS28. Comparison with previous studies revealed a reduction in disease activity of prevalent RA cases, possibly resulting from increased use of aggressive anti-rheumatic treatments.

Long-term prednisone in doses of less than 5 mg/day for treatment of rheumatoid arthritis: personal experience over 25 years.

This article summarises the experience of one academic rheumatologist in treatment of patients with rheumatoid arthritis (RA) over 25 years from 1980-2004 with low-dose prednisone, most with <5 mg/day over long periods. A database was available which included medications and multidimensional health assessment questionnaire (MDHAQ) scores for physical function, pain, and routine assessment of patient index data (RAPID3), completed by all patients at all visits in the infrastructure of care. Most patients were treated with long-term low-dose prednisone, often from the initial visit and indefinitely, and with methotrexate after 1990. The mean initial prednisone dose declined from 10.3 mg/day in 1980-1984 to 3.6 mg/day in 2000-2004. Although no formal criteria were used to determine the initial dose, prednisone doses were higher in patients who had more severe MDHAQ/RAPID3 scores, as expected, reflecting confounding by indication. Similar improvements were seen in clinical status over 12 months in patients treated with <5 vs. ≥ 5 mg/day prednisone, and maintained for >8 years. Adverse effects were primarily bruising and skin-thinning, with low levels of hypertension, diabetes, and cataracts, although this information was based only on self-report rather than systematic assessment by a health professional. These data reflect limitations of observational data. However, a consecutive patient database may provide long-term information not available from clinical trials. The data document that prednisone at doses <5 mg/day over long periods appears acceptable and effective for many patients with RA at this time. Further clinical trials and long-term observational studies are needed to develop optimal treatment strategies for patients with RA with low-dose prednisone.

Finalisation and validation of the rheumatoid arthritis impact of disease score, a patient-derived composite measure of impact of rheumatoid arthritis: a EULAR initiative.

OBJECTIVE: A patient-derived composite measure of the impact of rheumatoid arthritis (RA), the rheumatoid arthritis impact of disease (RAID) score, takes into account pain, functional capacity, fatigue, physical and emotional wellbeing, quality of sleep and coping. The objectives were to finalise the RAID and examine its psychometric properties. METHODS: An international multicentre cross-sectional and longitudinal study of consecutive RA patients from 12 European countries was conducted to examine the psychometric properties of the different combinations of instruments that might be included within the RAID combinations scale (numeric rating scales (NRS) or various questionnaires). Construct validity was assessed cross-sectionally by Spearman correlation, reliability by intraclass correlation coefficient (ICC) in 50 stable patients, and sensitivity to change by standardised response means (SRM) in 88 patients whose treatment was intensified. RESULTS: 570 patients (79% women, mean ± SD age 56 ± 13 years, disease duration 12.5 ± 10.3 years, disease activity score (DAS28) 4.1 ± 1.6) participated in the validation study. NRS questions performed as well as longer combinations of questionnaires: the final RAID score is composed of seven NRS questions. The final RAID correlated strongly with patient global (R=0.76) and significantly also with other outcomes (DAS28 R=0.69, short form 36 physical -0.59 and mental -0.55, p<0.0001 for all). Reliability was high (ICC 0.90; 95% CI 0.84 to 0.94) and sensitivity to change was good (SRM 0.98 (0.96 to 1.00) compared with DAS28 SRM 1.06 (1.01 to 1.11)). CONCLUSION: The RAID score is a patient-derived composite score assessing the seven most important domains of impact of RA. This score is now validated; sensitivity to change should be further examined in larger studies.

Morning stiffness and other patient-reported outcomes of rheumatoid arthritis in clinical practice.

Morning stiffness has been recognized in traditional approaches to assessment of disease activity in rheumatoid arthritis (RA). Although morning stiffness is not specific to RA, changes in morning stiffness for an individual patient are helpful when monitoring health status. Health professionals can ask about morning stiffness but the most accurate and consistent approach to assessment from one visit to the next appears to be a patient self-report questionnaire. However, quantitative measures of patient-reported data are not an integral part of clinical monitoring in most clinics. No single measure is adequate for all individual patients, so quantitative measurement of patient-reported data should include many elements such as pain, functional status, fatigue, sleep, morning stiffness, work capacity, and physical and emotional well-being. In daily clinical practice, patient-reported outcomes can be collected easily using a standard questionnaire that patients can complete with pencil and paper or electronically on a touch screen in the waiting room. The results are then immediately available to the rheumatologists, to facilitate doctor-patient communication to improve the quality of patient care, leading to better patient outcomes.

Increases in use of methotrexate since the 1980s.

In this chapter, we review the use of DMARDs in several clinical RA cohorts and databases between the 1970s and the 2000s. The DMARD profile in the QUEST-RA database provides an overview of clinical use of MTX in recent years in 25 countries. The data show that (I) MTX is currently the most frequently used DMARD in RA, and (II) that this development has taken about 20 years to emerge.

Underestimation of the efficacy, effectiveness, tolerability, and safety of weekly low-dose methotrexate in information presented to physicians and patients.

Ten specific examples of the underestimation of the efficacy, effectiveness and tolerability, and overestimation of adverse events of weekly, low-dose methotrexate, administered with folic acid, in treatment of rheumatic diseases are summarised. These examples include: 1) meta-analyses of clinical trials suggest that methotrexate has an efficacy similar to other disease-modifying anti-rheumatic drugs (DMARDs); 2) information in textbooks and websites may overstate adverse events and drug interactions associated with weekly low-dose methotrexate; 3) information presented to patients when filling a prescription for methotrexate understates 'side effects' of RA and overstates those of methotrexate; 4) an admonition to patients to refrain entirely from consumption of alcohol while taking methotrexate may be unnecessary; 5) frequent blood testing in patients who take methotrexate may be overused; 6) eligibility of only a small minority of patients for clinical trials to compare biologic agents and methotrexate; 7) Step-up design in most comparisons of biologic agents with methotrexate includes only patients who had experienced an incomplete response to methotrexate; 8) in parallel design trials, the efficacy of biologic agents is not substantially greater than that of methotrexate; 9) low, inflexible dosage schedules of methotrexate and requirement for withdrawal with minimal liver function abnormalities in many clinical trials may underestimate efficacy, effectiveness, tolerability and safety; 10) interpretation of clinical trial results may overstate the clinical significance of lower radiographic progression in patients treated with biologic agents versus patients treated with methotrexate. More accurate interpretation of information for physicians and other health professionals, as well as patients, concerning use of weekly low-dose methotrexate in contemporary care could improve care and outcomes for patients with RA and other rheumatic diseases.

Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA Study.

OBJECTIVES: To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. METHODS: Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student's t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. RESULTS: A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. CONCLUSIONS: BMI appears to be associated with RA disease activity in women, but not in men.

Current evidence for a strategic approach to the management of rheumatoid arthritis with disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis.

OBJECTIVES: To perform a systematic literature review of effective strategies for the treatment of rheumatoid arthritis (RA). METHODS: As part of a European League Against Rheumatism (EULAR) Task Force investigation, a literature search was carried out from January 1962 until February 2009 in PubMed/Ovid Embase/Cochrane and EULAR/American College of Rheumatism (ACR)) abstracts (2007/2008) for studies with a treatment strategy adjusted to target a predefined outcome. Articles were systematically reviewed and clinical outcome, physical function and structural damage were compared between intensive and less intensive strategies. The results were evaluated by an expert panel to consolidate evidence on treatment strategies in RA. RESULTS: The search identified two different kinds of treatment strategies: strategies in which the reason for treatment adjustment differed between the study arms ('steering strategies', n=13) and strategies in which all trial arms used the same clinical outcome to adjust treatment with different pharmacological treatments ('medication strategies', n=7). Both intensive steering strategies and intensive medication strategies resulted in better outcome than less intensive strategies in patients with early active RA. CONCLUSION: Intensive steering strategies and intensive medication strategies produce a better clinical outcome, improved physical function and less structural damage than conventional steering or treatment. Proof in favour of any steering method is lacking and the best medication sequence is still not known.

Supervised machine learning and logistic regression identifies novel epistatic risk factors with PTPN22 for rheumatoid arthritis.

Investigating genetic interactions (epistasis) has proven difficult despite the recent advances of both laboratory methods and statistical developments. With no 'best' statistical approach available, combining several analytical methods may be optimal for detecting epistatic interactions. Using a multi-stage analysis that incorporated supervised machine learning and methods of association testing, we investigated epistatic interactions with a well-established genetic factor (PTPN22 1858T) in a complex autoimmune disease (rheumatoid arthritis (RA)). Our analysis consisted of four principal stages: Stage I (data reduction)-identifying candidate chromosomal regions in 292 affected sibling pairs, by predicting PTPN22 concordance using multipoint identity-by-descent probabilities and a supervised machine learning algorithm (Random Forests); Stage II (extension analysis)-testing detailed genetic data within candidate chromosomal regions for epistasis with PTPN22 1858T in 677 cases and 750 controls using logistic regression; Stage III (replication analysis)-confirmation of epistatic interactions in 947 cases and 1756 controls; Stage IV (combined analysis)-a pooled analysis including all 1624 RA cases and 2506 control subjects for final estimates of effect size. A total of seven replicating epistatic interactions were identified. SNP variants within CDH13, MYO3A, CEP72 and near WFDC1 showed significant evidence for interaction with PTPN22, affecting susceptibility to RA.

Smokers and non smokers with rheumatoid arthritis have similar clinical status: data from the multinational QUEST-RA database.

OBJECTIVES: To analyse clinical severity/activity of rheumatoid arthritis (RA) according to smoking status. METHODS: The QUEST-RA multinational database reviews patients for Core Data Set measures including 28 swollen and tender joint count, physician global estimate, erythrocyte sedimentation rate (ESR), HAQ-function, pain, and patient global estimate, as well as DAS28, rheumatoid factor (RF), nodules, erosions and number of DMARDs were recorded. Smoking status was assessed by self-report as 'never smoked', 'currently smoking' and 'former smokers'. Patient groups with different smoking status were compared for demographic and RA measures. RESULTS: Among the 7,307 patients with smoking data available, status as 'never smoked,' 'current smoker' and 'former smoker' were reported by 65%, 15% and 20%. Ever smokers were more likely to be RF-positive (OR 1.32;1.17-1.48, p<0.001). Rheumatoid nodules were more frequent in ever smokers (OR 1.41;1.24-1.59, p<0.001). The percentage of patients with erosive arthritis and extra-articular disease was similar in all smoking categories. Mean DAS28 was 4.4 (SD 1.6) in non-smokers vs. 4.0 (SD 1.6) in those who had ever smoked. However, when adjusted by age, sex, disease duration, and country gross domestic product, only ESR remained significantly different among Core Data Set measures (mean 31.7mm in non-smokers vs. 26.8mm in ever smoked category). CONCLUSIONS: RA patients who had ever smoked were more likely to have RF and nodules, but values for other clinical status measures were similar in all smoking categories (never smoked, current smokers and former smokers).

Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database.

OBJECTIVE: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. METHODS: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000. RESULTS: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. CONCLUSIONS: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

Elaboration of the preliminary Rheumatoid Arthritis Impact of Disease (RAID) score: a EULAR initiative.

BACKGROUND: Current response criteria in rheumatoid arthritis (RA) usually assess only three patient-reported outcomes (PROs): pain, functional disability and patient global assessment. Other important PROs such as fatigue are not included. OBJECTIVE: To elaborate a patient-derived composite response index for use in clinical trials in RA, the RA Impact of Disease (RAID) score. METHODS: Ten patients identified 17 domains or areas of health relevant for inclusion in the score, then 96 patients (10 per country in 10 European countries) ranked these domains in order of decreasing importance. The seven most important domains were selected. Instruments were chosen for each domain after extensive literature research of psychometric properties and expert opinion. The relative weight of each of the domains was obtained from 505 patients who were asked to "distribute 100 points" among the seven domains. The average ranks of importance of these domains were then computed. RESULTS: The RAID score includes seven domains with the following relative weights: pain (21%), functional disability (16%), fatigue (15%), emotional well-being (12%), sleep (12%), coping (12%) and physical well-being (12%). Weights were similar across countries and across patient and disease characteristics. Proposed instruments include the Health Assessment Questionnaire and numerical ratings scales. CONCLUSION: The preliminary RAID score is a patient-derived weighted score to assess the impact of RA. An ongoing study will allow the final choice of questionnaires and assessment of validity. This score can be used in clinical trials as a new composite index that captures information relevant to patients.

Efficacy of prednisone 1-4 mg/day in patients with rheumatoid arthritis: a randomised, double-blind, placebo controlled withdrawal clinical trial.

OBJECTIVE: A randomised double-blind placebo controlled withdrawal clinical trial of prednisone versus placebo in patients with rheumatoid arthritis (RA), treated in usual clinical care with 1-4 mg/day prednisone, withdrawn to the same dose of 1 mg prednisone or identical placebo tablets. METHODS: All patients were from one academic setting and all trial visits were conducted in usual clinical care. Patients were taking stable doses of 1-4 mg prednisone with stable clinical status, documented quantitatively by patient questionnaire scores. The protocol included three phases: (1) equivalence: 1-4 study prednisone 1 mg tablets taken for 12 weeks to ascertain their efficacy compared with the patient's usual tablets before randomisation; (2) transfer: substitution of a 1 mg prednisone or identical placebo tablet every 4 weeks (over 0-12 weeks) to the same number as baseline prednisone; (3) comparison: observation over 24 subsequent weeks taking the same number of either placebo or prednisone tablets as at baseline. The primary outcome was withdrawal due to patient-reported lack of efficacy versus continuation in the trial for 24 weeks. RESULTS: Thirty-one patients were randomised, 15 to prednisone and 16 to placebo, with three administrative discontinuations. In "intent-to-treat" analyses, 3/15 prednisone and 11/16 placebo participants withdrew (p = 0.03). Among participants eligible for the primary outcome, 3/13 prednisone and 11/15 placebo participants withdrew for lack of efficacy (p = 0.02). No meaningful adverse events were reported, as anticipated. CONCLUSION: Efficacy of 1-4 mg prednisone was documented. Evidence of statistically significant differences with only 31 patients may suggest a robust treatment effect.

Should an order to "monitor long-term vital signs," including mortality outcomes, be as routine as an order for a laboratory test in patients with rheumatic diseases?

Vital signs alert a health professional to problems which may threaten patient well-being and survival. Clinicians are highly familiar with vital signs for acute disease such as blood pressure, pulse, temperature, but unfamiliar with vital signs for chronic disease, such as physical function, pain, global status, exercise frequency and smoking. Long-term vital signs should be collected at each visit and stored in a computer database, ideally in a flow sheet format, as the memory of clinicians and patients is not reliable over long periods. The structure of the database should be identical from one site to another, so that data may be pooled to analyze large series of patients, particularly those with rare diseases, such as systemic sclerosis, polymyositis, and vasculitis. Of course, appropriate additional information beyond simple "long-term vital signs" from a physical examination, radiograph and laboratory are needed for further accurate assessment of prognosis and outcomes, in both acute and chronic diseases, and optimal information will emerge from specialized research centers. A common long-term vital signs database would be a major advance from current descriptive, non-quantitative monitoring of patients with rheumatic diseases, and would allow any rheumatologist to contribute to improved knowledge and mortality outcomes of rheumatic diseases.

Mortality in rheumatoid arthritis: 2008 update.

Mortality rates in patients with rheumatoid arthritis (RA) are 1.5-1.6 fold higher than in the general population, with similar patterns over 60 years. The acute attributed causes of death appear overall similar to the general population, with cardiovascular disease the most common attributed cause of death, and with more infection, pulmonary and renal disease in RA than in the general population. All clinical measures indicating more severe clinical status appear prognostic of premature mortality, with rheumatoid factor and the shared epitope significant for progressive RA. Functional and global measures as well as comorbidities generally are the most significant predictors of premature death.

Poor physical fitness and performance as predictors of mortality in normal populations and patients with rheumatic and other diseases.

Poor physical function and low muscle strength are significant predictors of mortality in rheumatoid arthritis, other chronic diseases, ageing individuals, and the general population. Poor physical function predicts earlier mortality in diseased and normal populations at levels of significance similar to or greater than most known biomedical predictors such as laboratory tests. This chapter summarizes data concerning the prediction of premature mortality by poor physical fitness and musculoskeletal function, according to performance and self-report measures. The data support recommendations for regular exercise in all individuals whether or not they have a disease, to promote health and longevity.