Rheumatoid Arthritis: Michaud K

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D, Anonymous00358, Anonymous00359. · Medical University of Vienna, Vienna, Austria. · Arthritis Rheum. · Pubmed #18821648 No free full text.

Abstract: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardized operating procedures, which use a three-step approach: 1) expert-based definition of relevant research questions (November 2006); 2) systematic literature search (November 2006 to May 2007); and 3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue. CONCLUSION: These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Wolfe F, Caplan L, Michaud K. · No affiliation provided · J Rheumatol. · Pubmed #15570626 links to  free full text

This publication has no abstract.

Michaud K, Bombardier C, Emery P. · Section of Rheumatology and Immunology, University of Nebraska Medical Center, Omaha, NE 68198-6270, USA. · Clin Exp Rheumatol. · Pubmed #17977487 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease that, in addition to causing joint damage, is associated with pain, fatigue, disability and functional loss, which can substantially decrease a patient's quality of life (QoL). Along with improvements in signs and symptoms, QoL benefits have become increasingly important in optimizing treatment outcomes in RA. Measurements of QoL have previously been under-used in all areas of medicine and only recently have clinical trials included them as a measure of treatment effectiveness. The existence of a positive relationship between improvements in signs and symptoms and concomitant improvements in QoL provides additional evidence that QoL measures are useful benchmarks for evaluating the effectiveness of treatment for RA. Furthermore, since these outcome measures evaluate the real-life, patient-centered benefits of RA therapies, they are likely to become increasingly central to the assessment of disease impact in clinical trials and practice, and to both drug approval and reimbursement decisions.This article reviews the impact of abatacept, a selective co-stimulation modulator, on the QoL of patients with active RA across a number of pivotal clinical trials. Firstly, an overview of the key QoL measurements used in abatacept clinical trials is provided, including those such as the Short Form-36, Health Assessment Questionnaire and Visual Analog Scale for pain, sleep and fatigue. We then present QoL data obtained in a wide range of patients with RA, including those with an inadequate response to either methotrexate or anti-tumor necrosis factor therapy, who have been treated with abatacept. Analysis of these data demonstrates that abatacept therapy has the potential to improve QoL across a range of patients with RA.

Michaud K, Wolfe F. · University of Nebraska Medical Center, Omaha, Nebraska 68198-6270, USA. · Best Pract Res Clin Rheumatol. · Pubmed #17870034 No free full text.

Abstract: Rheumatoid arthritis (RA) is often characterized by the burden of swollen joints, pain, and decreased physical function, but less understood are the many manifestations of additional health conditions that are associated with RA and its treatments. First brought to light with observations of increased mortality in RA, studies noted the increased rates of cardiovascular and infection events. The chronic, debilitating, autoimmune nature of RA affects the patient directly or indirectly in almost all organ systems, from cardiovascular problems and infections to depression and gastrointestinal ulcers. On average, the established RA patient has two or more comorbid conditions. It should be the responsibility of the rheumatologist to take these and the risk of additional conditions into account when treating the patient. This chapter reviews important comorbidities in patients with RA, their prevalence, and their relation to RA.

Benito-Garcia E, Michaud K, Wolfe F. · Department of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA. · J Rheumatol. · Pubmed #17611980 No free full text.

Abstract: OBJECTIVE: To evaluate the risk of gastrointestinal (GI) symptoms and ulcers associated to the use of low-dose aspirin (ASA) among patients with rheumatoid arthritis (RA) and osteoarthritis (OA) treated with cyclooxygenase-2 (COX-2) drugs, to clarify the controversy in the literature. METHODS: Using a longitudinal databank, a prospective study using Cox proportional hazards models was performed in patients receiving COX-2 therapy for RA or OA to examine the effect of ASA on GI events. In 4 separate analyses patients reported dyspeptic symptoms and GI ulcers at semiannual intervals for up to 3 years. Ulcers were validated by review of medical records. RESULTS: Among 4240 patients taking COX-2-specific inhibitors, with no ulcer at study start, the age- and sex-adjusted hazard ratios for the effect of ASA on the development of epigastric pain, heartburn, nausea, and ulcers, without these previous events, were 1.11 (95% CI 0.97-1.29), 1.00 (95% CI 0.88-1.15), 1.32 (95% CI 1.13-1.54), and 1.27 (95% CI 0.78-2.05). The use of a propensity score to account for the risk of ASA prescription showed an even lower effect of ASA among all GI variables. This risk occurs within the setting of no prior GI symptoms or GI events, and independently of the use of proton pump inhibitors, other GI drugs, other nonsteroidal antiinflammatory drugs, prednisone, or methotrexate. CONCLUSION: In actual practice, the use of low-dose ASA has a small effect on the risk of developing dyspeptic symptoms in a group of patients with rheumatic disease.

Wolfe F, Michaud K, Pincus T. · Arthritis Research Center Foundation, University of Kansas School of Medicine, Wichita, KS 67214, USA. · J Rheumatol. · Pubmed #15996062 No free full text.

Abstract: OBJECTIVE: Key outcomes in rheumatoid arthritis (RA) are evaluated with multi-item ratings scales such as the Health Assessment Questionnaire (HAQ) and visual analog scales (VAS) such as pain and patient and physician global. As VAS scales are easy to use and particularly effective in research and patient care, we studied the characteristics, association, and psychometric properties of a VAS function scale (VAS-F) to determine if it could be used in RA studies and clinical practice. METHODS: A total of 394 patients with RA completed the HAQ, the HAQ-II, and a VAS functional scale. In addition, they completed standard assessments of pain, global, fatigue, sleep problems, joint count, and the Medical Outcome Study Short-Form 36 (SF-36) physical component summary score (PCS) and vitality and total pain scores. RESULTS: The HAQ-II was correlated with VAS-F at 0.76, but distributional characteristics of the HAQ and VAS-F differed, as the VAS-F scale results contained more higher scores as well as more lower scores compared with the HAQ-II and HAQ. Kendall's tau concordance analyses indicated that VAS scales were more concordant with other VAS than with non-VAS scales. Concordance of VAS-F was greatest with VAS global and was similar overall with VAS pain, sleep disturbance, fatigue, and quality of life. By contrast, the PCS, a multi-item scale, was more concordant with HAQ-II and HAQ. There was little to no difference between the VAS-F and the 2 HAQ with regard to concordance with the multi-item joint count, SF-36 vitality, and SF-36 total pain. CONCLUSION: The distribution differences between HAQ and HAQ-II and the VAS-F suggest that patients do not see minor limitations as problematic, but rate major limitations as being particularly limiting and worthy of high ratings. A VAS functional scale represents a patient-weighted functional assessment in which additional interpretation is given to the meaning of the limitations by the patient. VAS-F scales may be suitable for use in the clinic and in research. However, studies to assess sensitivity to change are required to determine the appropriate role of this scale.

Wolfe F, Michaud K. · Arthritis Research Center Foundation, University of Kansas School of Medicine, Wichita, Kansas 67214, USA. · J Rheumatol. · Pubmed #15517621 No free full text.

Abstract: OBJECTIVE: Fatigue is a common and distressing symptom in patients with rheumatoid arthritis (RA) and other rheumatic diseases. Reports have suggested profound improvements in fatigue after onset of anti-tumor necrosis factor-alpha (anti-TNF) therapy. In addition, physician and patient groups now identify fatigue as a very important symptom. However, data to support these observations are lacking. We evaluate the importance of fatigue in relation to other measures of clinical status, describe predictors of fatigue, and investigate fatigue levels in patients treated with anti-TNF therapy. METHODS: A total of 852 patients participated in a symptom-importance preference study. Additional analyses of fatigue and other clinical status variables were performed in up to 21,016 patients with RA and 3815 patients with osteoarthritis (OA) participating in the National Data Bank for Rheumatic Diseases. RESULTS: In ranking studies of the relative importance of fatigue compared with function, pain, cognition, gastrointestinal symptoms, and sleep, 8.0% of patients ranked fatigue as the most important variable, compared with 32.1% for function and 21.5% for pain. Multivariable studies of clinical change over 6 months found that changes in fatigue were weakly associated with changes in health status, in contradistinction to results for pain, function, and depression. Fatigue levels and fatigue predictors were similar in RA and OA patients. RA patients treated with anti-TNF therapy did not have lower fatigue scores compared with those not treated with this type of therapy. CONCLUSION: Among RA patient self-report measures, fatigue is not ranked as important as functional disability, pain, or depression by most patients. This relative ranking is confirmed by examination of clinical improvement data. Fatigue levels and predictors of fatigue are essentially the same in RA and OA. Although anti-TNF therapy lowers fatigue levels, there is no evidence that this effect is greater for anti-TNF therapy than for other RA treatments.

Gabriel SE, Michaud K. · Department of Health Sciences Research, Mayo Foundation, Rochester, MN 55905, USA. · Arthritis Res Ther. · Pubmed #19519924 links to  free full text

Abstract: 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, Sjögren's 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.

Wolfe F, Michaud K. · University of Kansas School of Medicine and National Data Bank for Rheumatic Diseases, Wichita, Kansas. · Arthritis Rheum. · Pubmed #19404997 No free full text.

Abstract: 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 patient's global health and associated perceptions.

Wolfe F, Boers M, Felson D, Michaud K, Wells GA. · National Data Bank for Rheumatic Diseases and University ofKansas School of Medicine, Wichita, Kansas 67214, USA. · J Rheumatol. · Pubmed #19332634 No free full text.

Abstract: OBJECTIVE: To examine the prevalence of remission in rheumatoid arthritis (RA) as determined by physicians and patients independently, and to determine the degree of agreement among methods, the strength of predictor variables of remission, and the length of remission. METHODS: Eight hundred patients with RA completed a remission questionnaire on the day of their rheumatologist visit and their rheumatologists completed a separate questionnaire the same day. The question(s) were: "Given all your experience with disease activity in RA, are you [is your patient] currently in remission?". Patients also completed 0-10 visual analog scales for RA activity, pain, and functional limitation. RESULTS: The percentage of patients in remission by physician and patient assessment was 34.8% [95% confidence interval (CI) 31.4-38.2] and 30.9% (95% CI 27.7-34.20), respectively. The percentage of patients classified concordantly (full agreement) was 78.6%, and the associated kappa statistic was 0.54 (95% CI 0.45-0.58). The median duration of remission was 2.0 years. The median RA activity, pain, and functional scores were 1.0, 1.5, and 1.25 for patient-determined remission and 1.5, 1.5, and 1.5 for physician-determined remission. CONCLUSION: Physician and patient estimates of remission in RA are similar (34.8% to 30.9%), and agreement was 78.6% (kappa 0.53). Based on previous data and the observed presence of disease activity, this definition of remission appears to be a measure of minimal disease activity rather than true remission. The problem of remission rates will not be solved until a consensus definition that has relevance in research and the clinic is developed.

Wolfe F, Michaud K. · National Data Bank for Rheumatic Diseases, 1035 N. Emporia, Suite 288, Wichita, KS 67214, USA. · J Rheumatol. · Pubmed #19228653 No free full text.

Abstract: OBJECTIVE: To compare outcome-predictor relationships in fibromyalgia (FM) and rheumatoid arthritis (RA), to provide information regarding the competing hypotheses that FM is a continuum or a discrete disorder. METHODS: We studied 3 outcome variables (work disability, opioid use, depression) and 12 clinical predictor variables in 2,046 patients with FM and 20,374 with RA. We determined whether outcome-predictor relationships were stronger in FM or RA by measuring the areas under the receiver-operating curves. We used fractional polynomial logistic regression to create graphic models for the outcome-predictor relationships. RESULTS: All measures of status and outcome were more abnormal in FM than in RA. Depression was reported in 33.4% of patients with FM compared with 15.1% of those with RA. The predictor-outcome relationship was significantly stronger in RA in 28 of the 36 tests, and not different in the remainder. The relationship between outcome and predictor variables was generally similar in patients with FM and RA. However, unmodeled depression that was not explained by study variables was noted in FM. CONCLUSION: Our data are consistent with the hypothesis that FM is the end of a severity continuum, but that additional psychological factors are an integral part of the syndrome.

Wolfe F, Michaud K. · National Data Bank for Rheumatic Diseases, 1035 N. Emporia, Suite 288, Wichita, KS 67214, USA. · J Rheumatol. · Pubmed #19040313 No free full text.

Abstract: OBJECTIVE: Patients with rheumatoid arthritis (RA) and their physicians often disagree as to the success of RA treatment or RA outcomes. However, guidelines (such as EULAR criteria for DAS scores) are heavily weighted toward joint counts and laboratory tests, and no guidelines exist for patient reported outcomes. Our aims were (1) to provide a patient-based definition of successful RA outcome or of treatment success and failure; (2) to describe the characteristics of patients meeting this definition; (3) to describe how external states such as disability and comorbidity influence definitions of health outcome; and (4) to derive surrogate-measure cutpoints for the definition. METHODS: A total of 20,268 patients with RA (5132 without comorbidity) were studied by recursive partitioning and regression methods to determine best dividing points between RA treatment and outcome success and non-success using 0-10 visual analog scales (VAS) for patient global assessment, pain, fatigue, and RA activity, and a Health Assessment Questionnaire (HAQ) scale. RESULTS: 14.5% of all patients and 22.9% of those without comorbidity were very satisfied with their health (success). Patient global at a level<or=1.25 best separated success from failure. Mean and median scores for those who were very satisfied were HAQ (0-3 scale) 0.36, 0.12; pain (0-10) 1.1, 0.5; global (0-10) 0.9, 0.5; and fatigue (0-10) 1.5, 1.0. VAS scores increased by approximately 0.5 units for each comorbid condition. CONCLUSION: Patient global at a level<or=1.25 best separates patients who are very satisfied with their health from those not very satisfied, regardless of the presence of comorbidity. All scores increase with increasing comorbidity, which must be accounted for when assessing individual patients. Values identified here suggest patients require better outcomes than are found in patients who are in Disease Activity Score-28 remission or OMERACT low disease activity states.

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D. · Division of Rheumatology, Medical University of Vienna, Vienna, Austria. · Ann Rheum Dis. · Pubmed #18791055 No free full text.

Abstract: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue. CONCLUSIONS: These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Wolfe F, Michaud K. · National Data Bank for Rheumatic Diseases, Wichita, Kansas, and University of Kansas School of Medicine, Wichita. · Arthritis Rheum. · Pubmed #18759273 No free full text.

Abstract: 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.

Nadareishvili Z, Michaud K, Hallenbeck JM, Wolfe F. · Georgetown University Hospital, Washington, DC, USA. · Arthritis Rheum. · Pubmed #18668583 No free full text.

Abstract: 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.

Wolfe F, Michaud K. · National Data Bank for Rheumatic Diseases, and University of Kansas School of Medicine, Wichita, KS 67214, USA. · Nat Clin Pract Rheumatol. · Pubmed #18628729 No free full text.

This publication has no abstract.

Wolfe F, Michaud K. · National Data Bank for Rheumatic Diseases, 1035 N. Emporia, Suite 288, Wichita, KS 67214, USA. · J Rheumatol. · Pubmed #18484696 No free full text.

Abstract: OBJECTIVE: To determine, primarily in rheumatoid arthritis (RA), the prevalence, relative risk, and risk factors for oral and ocular dryness. METHODS: We studied self-reported persistent ocular and oral dryness (PD) present in 2 consecutive observations, and sporadic dryness (SD) present in 1 of 2 consecutive observations, during semiannual assessments in 9921 patients with RA and in 2851 with a noninflammatory rheumatic disorder (NIRD) (not fibromyalgia; FM). We also evaluated prevalence in 2867 patients with FM. RESULTS: In RA, PD was noted in 11.6% and SD in 17.5%. Compared with NIRD, the age and sex adjusted relative risk (RR) for PD was 1.34 (95% CI 1.17-1.51) and the severity and treatment adjusted RR was 1.46 (95% CI 1.26-1.6). The adjusted RR for FM compared with RA and NIRD was 2.02 (95% CI 1.85-2.20). Dryness prevalence increased 10% to 13% every 10 years, and was associated with therapy. The treatment attributable risk was 27.5%. Fatigue and body pain (Symptom Intensity Scale) was more strongly associated with dryness than was any other clinical scale, including Health Assessment Questionnaire, pain, and Medical Outcomes Study Short Form-36 Health Survey. SD was associated with a covariate adjusted decrease in quality of life of 0.020 (95% CI 0.012-0.029) utility units. CONCLUSION: Dryness is increased in RA and is contributed to by severity and therapy. The combination of body pain and fatigue is the strongest clinical correlate of dryness, and is independent of diagnosis of FM. Any factor that increases illness severity or distress results in an increase in dryness.

Shaver TS, Anderson JD, Weidensaul DN, Shahouri SS, Busch RE, Mikuls TR, Michaud K, Wolfe F. · Arthritis and Rheumatology Clinics of Kansas, USA. · J Rheumatol. · Pubmed #18412311 No free full text.

Abstract: OBJECTIVE: To investigate the results and feasibility of available scales to measure minimal disease activity (MDA) and remission in rheumatoid arthritis (RA) in the clinic. METHODS: We studied 849 consecutive patients with RA seen in a community rheumatology practice for routine RA care by 4 rheumatologists, beginning in March 2007 and ending in August 2007. Patients and physicians completed a simple form at each visit. We calculated the Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI), physician assessment of global activity, and the Patient Activity Scale (PAS-II). From these we calculated remission and MDA prevalence in this community practice. RESULTS: The DAS28 could not be determined in more than 50% of patients because of referring physician and insurance company restrictions. Remission prevalences differed by assessment method: DAS28 28.5%, CDAI 6.5%-8.1%, physician global 12.5%, PAS 13.7%. MDA was 26.9% using the American College of Rheumatology core set variables, 34.7% using the DAS28, and 26.8% using the PAS-II. The kappa statistic was only fair (0.2 to 0.4) for most comparisons between assessment methods. No significant differences were noted for remission and MDA according to biologic therapy. CONCLUSION: The CDAI and/or physician global and PAS-II are simple acceptable ways to measure RA activity in the clinic, but results differ strikingly according to method. Further standardization appears to be required for full implementation of the CDAI. Caution is urged before using these methods for regulatory purposes.

Wailoo AJ, Bansback N, Brennan A, Michaud K, Nixon RM, Wolfe F. · Health Economics and Decision Science, ScHARR, University of Sheffield, Sheffield, UK. · Arthritis Rheum. · Pubmed #18383356 links to  free full text

Abstract: OBJECTIVE: Since the introduction of the Medicare Prescription Drug Improvement and Modernization Act and its associated demonstration project, coverage of selected biologic drugs has been expanded for Medicare beneficiaries. For rheumatoid arthritis, coverage was extended to etanercept, adalimumab, and anakinra in addition to the previously covered infliximab. We undertook to develop a model to compare the costs and quality-adjusted life years (QALYs) generated by each of the 4 biologic agents. METHODS: Data were drawn from meta-analysis of randomized controlled trials and from a large longitudinal outcomes databank. Uncertainty was addressed using probabilistic and one-way sensitivity analyses. A lifetime horizon and Medicare viewpoint were adopted. RESULTS: In the base case analysis, anakinra was the least effective and least costly strategy. Etanercept, adalimumab, and infliximab were similar in terms of effectiveness, but infliximab was more costly. If decision makers are willing to pay a maximum of $50,000/QALY, the probability that infliximab is cost-effective is <1%. Findings were robust to a range of sensitivity analyses. Only if the dose of infliximab remains constant over time is this likely to be a cost-effective strategy. CONCLUSION: Infliximab is unlikely to be cost-effective in the Medicare population compared with either etanercept or adalimumab. Anakinra is substantially less costly but is also less effective than the 3 tumor necrosis factor alpha inhibitors.

Wolfe F, Allaire S, Michaud K. · National Data Bank for Rheumatic Diseases, 1035 N. Emporia, Wichita, KS 67214, USA. · J Rheumatol. · Pubmed #17787043 No free full text.

Abstract: OBJECTIVE: To determine the prevalence and incidence rates of work disability in rheumatoid arthritis (RA), and to determine the effect of anti-tumor necrosis factor (TNF) therapy on work disability. METHODS: Participants with RA who were employed when RA was diagnosed (N = 8082) were evaluated for up to 5.5 years. Work disability incidence rates were determined in a subset (N = 4155) of those who stated they were currently employed, and the effect of anti-TNF therapy was determined by conditional logistic regression, after adjustment for covariates. RESULTS: At a median of 12.8 years after RA onset, 56.2% were still employed and 43.8% were not working. Of those not working, 22.7% considered themselves disabled. In addition, 30.5% had stopped work over their lifetimes for health reasons and 20.6% were currently receiving Social Security disability benefits. The annualized incidence rate for self-reported disability was 2.5% and for Social Security disability 1.9%. The incidence rate for persons who stopped working and did not resume employment was 4.0%. Anti-TNF therapy was not associated with Social Security disability, but was associated with an increased risk of self-reported disability (odds ratio 1.6) after adjustment for covariates. CONCLUSION: Rates of self-reported disability were lower than noted in previous studies, perhaps reflecting overall improvement in RA therapy. We could not discern a positive effect of anti-TNF therapy on the risk of work disability.

Wolfe F, Michaud K. · National Data Bank for Rheumatic Diseases and University of Kansas School of Medicine, Wichita, KS 67214, USA. · Arthritis Rheum. · Pubmed #17729297 links to  free full text

Abstract: OBJECTIVE: Induction of malignancy is a major concern when rheumatoid arthritis (RA) is treated with biologic therapy. A meta-analysis of RA biologic clinical trials found a general increased risk of malignancy, but this risk was not found in a large observational study. We undertook this study to assess the risk of malignancy among biologic-treated patients in a large US observational database. METHODS: We studied incident cases of cancer among 13,001 patients during approximately 49,000 patient-years of observation in the years 1998-2005. Cancer rates were compared with population rates using the US National Cancer Institute SEER (Surveillance, Epidemiology, and End-Results) database. Assessment of the risk of biologic therapy utilized conditional logistic regression to calculate odds ratios (ORs) as estimates of the relative risk, further adjusted for 6 confounders: age, sex, education level, smoking history, RA severity, and prednisone use. RESULTS: Biologic exposure was 49%. There were 623 incident cases of nonmelanotic skin cancer and 537 other cancers. The standardized incidence ratios and 95% confidence intervals (95% CIs) compared with SEER data were as follows: all cancers 1.0 (1.0-1.1), breast 0.8 (0.6-0.9), colon 0.5 (0.4-0.6), lung 1.2 (1.0-1.4), lymphoma 1.7 (1.3-2.2). Biologics were associated with an increased risk of nonmelanotic skin cancer (OR 1.5, 95% CI 1.2-1.8) and melanoma (OR 2.3, 95% CI 0.9-5.4). No other malignancy was associated with biologic use; the OR (overall risk) of any cancer was 1.0 (95% CI 0.8-1.2). CONCLUSION: Biologic therapy is associated with increased risk for skin cancers, but not for solid tumors or lymphoproliferative malignancies. These associations were consistent across different biologic therapies.

Wolfe F, Rasker JJ, Boers M, Wells GA, Michaud K. · National Data Bank for Rheumatic Diseases, Wichita, Kansas 67214, USA. · Arthritis Rheum. · Pubmed #17665487 links to  free full text

Abstract: OBJECTIVE: To determine the prevalence of minimal disease activity (MDA) and remission in patients with rheumatoid arthritis (RA), to assess the effect of anti-tumor necrosis factor (anti-TNF) therapy on MDA, and to determine the extent to which MDA status improves long-term outcomes. METHODS: Using the Patient Activity Scale (PAS) as a surrogate, we assessed the prevalence of MDA and remission in 18,062 patients with RA using the newly developed Outcome Measures in Rheumatology Clinical Trials (OMERACT) criteria for MDA. RESULTS: MDA was noted in 20.2% of 18,062 patients and persistent MDA, operationally defined as having MDA during >or=2 consecutive 6-month observation periods, occurred in 13.5% of 7,433 patients followed longitudinally. Disease activity at remission levels was noted in 7%. Among patients with MDA, 82% received disease-modifying antirheumatic drugs or biologic agents. Following anti-TNF initiation, the cumulative probability of achieving MDA at 2 and 6 years was 4.1% and 7.6%, respectively, and persistent MDA probabilities were 2.7% and 4.5%, respectively. Regardless of RA duration, patients with MDA had substantially better outcomes, including a 10-fold reduction in work disability and an approximately 2-fold reduction in total joint replacement and mortality. CONCLUSION: Remission remains uncommon in RA, and the prevalence of new remission in community practice is substantially lower than noted in published trials of biologic therapy. On average, persons with MDA appear to have persistently mild RA. This might be the effect of milder RA and/or more effective treatment in early RA. The PAS had satisfactory levels of agreement with the full MDA criteria and appears suitable for use in clinical and epidemiologic research.

Wolfe F, Caplan L, Michaud K. · National Data Bank for Rheumatic Diseases, Arthritis Research Center Foundation, Wichita, KS 67214, USA. · Scand J Rheumatol. · Pubmed #17657669 No free full text.

Abstract: OBJECTIVES: Interstitial lung disease (ILD) is an important complication of rheumatoid arthritis (RA) or its treatment, and is associated with substantially increased mortality. Reports have suggested that infliximab with or without azathioprine might lead to rapidly progressive or fatal ILD. We used an RA data bank to assess the associations of treatments for RA and severe ILD. METHODS: ILD was identified in hospitalisations and death records in 100 of 17,598 RA patients and studied in relation to RA therapy with Cox regression analyses. RESULTS: The incidence of hospitalisation for ILD (HILD) was 260 per 100,000 patient years. Among those hospitalised for ILD, 27.0% died. In multivariable models of current and past RA treatment, the only current treatment associated with HILD was prednisone: hazard ratio (HR) 2.5 [95% confidence interval (CI) 1.5-4.1]. Among past therapies, prednisone (HR 3.0, 95% CI 1.0-8.9), infliximab (HR 2.1, 95% CI 1.1-3.8), etanercept (HR 1.7, 95% CI 1.0-3.0), and cyclophosphamide (HR 3.7, 95% CI 0.9-15.5) were associated with HILD. Pre-existing lung problems were identified in 67% of HILD. Only one case of HILD in the 100 hospitalisations suggested a possible temporal relationship between infliximab and HILD. CONCLUSIONS: Associations between RA treatment and HILD are confounded by the prescription of treatments for ILD such as prednisone, infliximab, etanercept, and cyclophosphamide. There is no clear pattern of causal association of treatment and ILD, and there is no clear evidence to support a causal relationship between infliximab, azathioprine, and HILD.

Wolfe F, Michaud K. · National Data Bank for Rheumatic Diseases, Arthritis Research Center Foundation, Wichita, Kansas 67214, USA. · J Rheumatol. · Pubmed #17611989 No free full text.

Abstract: OBJECTIVE: To compare a visual analog pain scale (VAS) with the Medical Outcomes Study Short Form-36 Health Survey (SF-36) bodily pain; to define the minimal clinically important change (MCIC) for pain in observational studies; to define clinically useful cutpoints for pain; to quantify the predictors of pain; and to estimate the effect of anti-tumor necrosis factor (TNF) therapy on pain. METHODS: Over 6 years we studied 12,090 patients with rheumatoid arthritis (RA). Pain was assessed by VAS and SF-36 pain scales. RESULTS: Compared with the SF-36 scale, the 0-10 VAS pain scale was better correlated with all clinical variables. The mean VAS score was 3.4 (standard deviation 2.8), and the best cutpoint for an "acceptable" level of pain was <or=2.0. The MCIC for pain was approximately 0.5 units by one measure and 1.1 by another. Pain increased slightly with the duration of RA, 0.03 (95% confidence interval 0.02-0.03) and decreased with age, 0.01 (95% CI 0.01-1.02) units per year. Pain was greater in ethnic minorities [0.78 (95% CI 0.63-0.93)] and women [0.31 (95% CI 0.23-0.39)] and was lower in college graduates [-0.88 (95% CI -1.00 to -0.76)]. Self-reported joint and nonarticular pain at 16 bilateral sites explained 44% of VAS pain scores. Anti-TNF therapy reduced pain by 0.59 to 0.53 units and EuroQol utility by 0.02 (95% CI 0.02-0.02) units. CONCLUSION: Anti-TNF therapy improved pain by 0.53 to 0.70 units. The MCIC for improvement and worsening of pain is about 0.5 to 1.1 units. Pain levels are almost constant over RA duration, and are increased in women, ethnic minorities, smokers, and those with less education.

Wolfe F, Michaud K. · National Data Bank for Rheumatic Diseases, Wichita, Kansas 67214, USA. · Arthritis Rheum. · Pubmed #17599730 links to  free full text

Abstract: OBJECTIVE: Despite advances in rheumatoid arthritis (RA) treatment, patients' decisions regarding therapy often deviate from expert recommendation. This study was undertaken to investigate patients' acceptance and satisfaction with therapy, willingness to change therapy, and reasons for not changing. METHODS: Participants (n = 6,135) completed an 11-item questionnaire concerning treatment preferences. Eight questions assessed reasons for not wanting to change therapy. The contribution of individual predictors was determined by logistic regression analysis. RESULTS: Questionnaire responses showed that 63.8% of the patients would not want to change therapy as long as their condition didn't get worse; 77.3% were satisfied with their medications, while 9.4% were dissatisfied. These assessments were weakly related to RA activity and functional status. Side effects had occurred in 22.4% of the patients during the previous 6 months, and in 65.5% at some period during their lifetime. Predictors of unwillingness to change therapy were satisfaction with RA control, which had an odds ratio (OR) of 6.8 (95% confidence interval [95% CI] 5.8-8.0), risk of side effects (OR 4.4 [95% CI 3.8-5.2]), physician opinion (OR 1.9 [95% CI 1.6-2.2]), fear of loss of control (OR 1.8 [95% CI 1.6-2.1]), lack of better medications (OR 1.4 [95% CI 1.2-1.6]), and costs (OR 1.3 [95% CI 1.1-1.6]). There was little difference in results between patients who were receiving biologic agents and those who were not. CONCLUSION: There is substantial discrepancy between declared satisfaction with therapy and measured RA activity and functional status. Most RA patients are satisfied with their therapy, even many with abnormal scores. Fear of loss of control of RA and fear of side effects are major patient concerns. Maintenance of current status, rather than future improvement, appears to be a high priority for patients.