Kaleb Michaud

Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases

Epidemiology is the study of the distribution and determinants of disease in human populations. Over the past decade there has been considerable progress in our understanding of the fundamental descriptive epidemiology (levels of disease frequency: incidence and prevalence, comorbidity, mortality, trends over time, geographic distributions, and clinical characteristics) of the rheumatic diseases. This progress is reviewed for the following major rheumatic diseases: rheumatoid arthritis (RA), juvenile rheumatoid arthritis, psoriatic arthritis, osteoarthritis, systemic lupus erythematosus, giant cell arteritis, polymyalgia rheumatica, gout, Sjögrens syndrome, and ankylosing spondylitis. These findings demonstrate the dynamic nature of the incidence and prevalence of these conditions – a reflection of the impact of genetic and environmental factors. The past decade has also brought new insights regarding the comorbidity associated with rheumatic diseases. Strong evidence now shows that persons with RA are at a high risk for developing several comorbid disorders, that these conditions may have atypical features and thus may be difficult to diagnose, and that persons with RA experience poorer outcomes after comorbidity compared with the general population. Taken together, these findings underscore the complexity of the rheumatic diseases and highlight the key role of epidemiological research in understanding these intriguing conditions.

American College of Rheumatology/European League Against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials

Objective Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a definition. Methods A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecified analyses from RA clinical trials. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to define remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate definitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analysed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes. Results Survey results for the definition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (eg, tender and swollen joint counts, C reactive protein (CRP) level, and global assessments on a 0–10 scale). Analyses suggested the need to include a patient-reported measure. Examination of 2-year follow-up data suggested that many candidate definitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score–based measures of remission did not predict good radiographic outcomes as well as the other candidate definitions did. Given these and other considerations, we propose that a patients RA can be defined as being in remission based on one of two definitions: (1) when scores on the tender joint count, swollen joint count, CRP (in mg/dl), and patient global assessment (0–10 scale) are all ≤1, or (2) when the score on the Simplified Disease Activity Index is ≤3.3. Conclusion We propose two new definitions of remission, both of which can be uniformly applied and widely used in RA clinical trials. The authors recommend that one of these be selected as an outcome measure in each trial and that the results on both be reported for each trial.

Rheumatoid Arthritis Disease Activity Measures: American College of Rheumatology Recommendations for Use in Clinical Practice

Although the systematic measurement of disease activity facilitates clinical decision making in rheumatoid arthritis (RA), no recommendations currently exist on which measures should be applied in clinical practice in the US. The American College of Rheumatology (ACR) convened a Working Group (WG) to comprehensively evaluate the validity, feasibility, and acceptability of available RA disease activity measures and derive recommendations for their use in clinical practice.

The risk of myocardial infarction and pharmacologic and nonpharmacologic myocardial infarction predictors in rheumatoid arthritis: A cohort and nested case–control analysis

OBJECTIVE To determine the risk of myocardial infarction (MI) in patients with rheumatoid arthritis (RA) compared with that in patients with noninflammatory rheumatic disorders and to determine risk factors for MI in RA, the relationship between cardiovascular risk factors and corticosteroid use, and the relationship between RA treatment and MI. METHODS We conducted a cohort study of MI in 17,738 patients with RA and 3,001 patients with noninflammatory rheumatic disorders who were assessed at 6-month intervals between 1999 and July 2006. We evaluated treatment effect in a nested case-control study of RA participants who were matched by age, sex, study duration, and date of study entry. RESULTS The covariate-adjusted risk of first MI in RA versus that in noninflammatory rheumatic disorders was 1.9 (95% confidence interval 1.2-2.9) (P = 0.005). In RA, MI was predicted by age, sex, education level, hypertension, smoking, exercise, prior MI, diabetes, a comorbidity index, use of low-dose aspirin and antilipemic agents, RA severity and treatment variables, and corticosteroid use. Except for obesity, predictors were of equal strength in RA and noninflammatory rheumatic disorders. The increased risk for MI in RA compared with that in noninflammatory rheumatic disorders lessened when corticosteroid users were excluded. Use of corticosteroids was associated with future development of diabetes and hypertension. CONCLUSION MI in RA is associated with demographic and cardiovascular risk factors and corticosteroid use. Study data support the hypothesis that RA activity causes MI and that corticosteroids are primarily a marker of RA activity. However, corticosteroids increase the risk of diabetes and hypertension and contribute to the overall risk of MI.

Predicting depression in rheumatoid arthritis: The signal importance of pain extent and fatigue, and comorbidity

OBJECTIVE To determine the incidence of self-reported depression (SRD) in rheumatoid arthritis and to identify and rank clinically useful predictors of depression. METHODS We assessed 22,131 patients for SRD between 1999 and 2008. We collected demographic, clinical and treatment data, household income, employment and work disability status, comorbidity, scales for function, pain, global, and fatigue, the Regional Pain Scale (RPS), the Symptom Intensity (SI) scale (a linear combination of the RPS and the fatigue scales) and linear combinations of the Health Assessment Questionnaire, pain and global severity. We used logistic regression analyses with multivariable fractional polynomial predictors, and Random Forest analysis to determine the importance of the predictors. RESULTS The cross-sectional prevalence of self-reported depression was 15.2% (95% confidence interval [95% CI] 14.7-15.7%) and the incidence rate was 5.5 (95% CI 5.3-5.7) per 100 patient years of observation. The cumulative risk of SRD after 9 years was 38.3% (95% CI 36.6-40.1%). Almost all variables were significant predictors in logistic models. In Random Forest analyses, the SI scale, followed by comorbidity, best predicted self-reported depression, and no other variable or combination of variables improved prediction compared with the SI scale. CONCLUSION Pain extent and fatigue (SI scale) are the dominant predictors of SRD. These variables, also of central importance in the symptomatology of fibromyalgia, are powerful markers of distress. A strong case can be made for the inclusion of these assessments in routine rheumatology practice. In addition, actual knowledge of comorbidity provides important insights into the patients global health and associated perceptions.

Chronic conditions and health problems in rheumatic diseases: comparisons with rheumatoid arthritis, noninflammatory rheumatic disorders, systemic lupus erythematosus, and fibromyalgia.

Objectives. To describe and compare the prevalence of lifetime and current self-reported comorbidity and associated quality of life in 4 rheumatic diseases, and to investigate comorbid conditions in light of the overlap between the index condition and comorbid conditions (CC), and in the context of symptom-type diagnoses. Methods. We studied comorbidity in 11,704 patients with fibromyalgia (FM), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and noninflammatory rheumatic disorders (NIRD). Patients completed semiannual self-reports relating to 22 present and past illnesses and completed the EuroQol (EQ-5D) utility index. Results. CC were most common in FM, followed by SLE. FM comorbidity was dominated by depression, mental illness, and symptom-type comorbidity (e.g., gastrointestinal and genitourinary disorders). In SLE, there were substantial increases in hypertension, depression, cataract, fractures, and cardiovascular and cerebrovascular, neurologic, lung, gall bladder and endocrine disorders compared with RA. Any current CC reduced the EQ-5D utility by 0.08 to 0.16 units. The lowest EQ-5D score was noted for current psychiatric illness (0.55) and current depression (0.60). Conclusion. Four patterns of comorbidity emerged: that associated with aging; that associated with aging but enhanced by the index condition, as in SLE and cardiovascular disease; comorbidity that is part of the symptoms complex of the index condition; and CC that represent lifetime traits or manifestations of the underlying illness. Depression was the most strongly associated correlate of EQ-5D quality of life, and current depression was present in about 15% of patients with RA or NIRD and 34% to 39% of those with SLE and FM.

Cardiovascular, rheumatologic, and pharmacologic predictors of stroke in patients with rheumatoid arthritis: A nested, case–control study†

OBJECTIVE To determine the risk of stroke in patients with rheumatoid arthritis (RA) and risk factors associated with stroke. METHODS We performed nested case-control analyses within a longitudinal databank, matching up to 20 controls for age, sex, and time of cohort entry to each patient with stroke. Conditional logistic regression was performed as an estimate of the relative risk of stroke in RA patients compared with those with noninflammatory rheumatic disorders, and to examine severity and anti-tumor necrosis factor (anti-TNF) treatment effects in RA. RESULTS We identified 269 patients with first-ever all-category strokes and 67 with ischemic stroke, including 41 in RA patients. The odds ratio (OR) for the risk of all-category stroke in RA was 1.64 (95% confidence interval [95% CI] 1.16-2.30, P = 0.005), and for ischemic stroke was 2.66 (95% CI 1.24-5.70, P = 0.012). Ischemic stroke was predicted by hypertension, myocardial infarction, low-dose aspirin, comorbidity score, Health Assessment Questionnaire score, and presence of total joint replacement, but not by diabetes, smoking, exercise, or body mass index. Adjusted for cardiovascular and RA risk factors, ischemic stroke was associated with rofecoxib (P = 0.060, OR 2.27 [95% CI 0.97-5.28]), and possibly with corticosteroid use. Anti-TNF therapy was not associated with ischemic stroke (P = 0.584, OR 0.80 [95% CI 0.34-1.82]). CONCLUSION RA is associated with increased risk of stroke, particularly ischemic stroke. Stroke is predicted by RA severity, certain cardiovascular risk factors, and comorbidity. Except for rofecoxib, RA treatment does not appear to be associated with stroke, although the effect of corticosteroids remains uncertain.

Rheumatoid factor as a potentiator of anti-citrullinated protein antibody-mediated inflammation in rheumatoid arthritis

The co‐occurrence of rheumatoid factor (RF) and anti–citrullinated protein antibody (ACPA) positivity in rheumatoid arthritis (RA) is well described. However, the mechanisms underlying the potential interaction between these 2 distinct autoantibodies have not been well defined. The aim of this study was to evaluate the epidemiologic and molecular interaction of ACPAs and RF and its association with both disease activity and measures of RA‐associated inflammation.

Effects of infertility, pregnancy loss, and patient concerns on family size of women with rheumatoid arthritis and systemic lupus erythematosus

Women with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have fewer children on average than other women. We sought to determine the roles of infertility, pregnancy loss, and personal choice on family size in women with these diseases.

Effect of body mass index on mortality and clinical status in rheumatoid arthritis

To study the relative risk (RR) of all‐cause and cause‐specific mortality in rheumatoid arthritis (RA) associated with body mass index (BMI), and to quantify the clinical and outcome consequences of abnormal BMI.