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ABSTRACT: OBJECTIVE: Rapidly predicting future outcomes based on short-term clinical response would be helpful to optimize rheumatoid arthritis (RA) management in early disease. Our aim was to derive and validate a clinical prediction rule to predict low disease activity (LDA) at 1 year among patients participating in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial escalating RA therapy by adding either etanercept or sulfasalazine + hydroxychloroquine [triple therapy (TT)] after 6 months of methotrexate (MTX) therapy. METHODS: Eligible subjects included in the derivation cohort (used for model building, n = 186) were participants with moderate or higher disease activity [Disease Activity Score 28-erythrocyte sedimentation rate (DAS-ESR) > 3.2] despite 24 weeks of MTX monotherapy who added either etanercept or sulfasalazine + hydroxychloroquine. Clinical characteristics measured within the next 12 weeks were used to predict LDA 1 year later using multivariable logistic regression. Validation was performed in the cohort of TEAR patients randomized to initially receive either MTX + etanercept or TT. RESULTS: The derivation cohort yielded 3 prediction models of varying complexity that included age, DAS28 at various timepoints, body mass index, and ESR (area under the receiver-operator characteristic curve up to 0.83). Accuracy of the prediction models ranged between 80% and 95% in both derivation and validation cohorts, depending on the complexity of the model and the cutpoints chosen for response and nonresponse. About 80% of patients could be predicted to be responders or nonresponders at Week 12. CONCLUSION: Clinical data collected early after starting or escalating disease-modifying antirheumatic drug/biologic treatment could accurately predict LDA at 1 year in patients with early RA. For patients predicted to be nonresponders, treatment could be changed at 12 weeks to optimize outcomes.
The Journal of Rheumatology 04/2013; · 3.69 Impact Factor
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ABSTRACT: Biomarkers such as interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R), and high sensitive C-reactive protein (hsCRP) have been reported to be elevated in acute myocardial infarction (AMI). The aim of this study is to determine the relationship between these markers during AMI, as well as their relationship to clinical parameters in an effort to discern their predictive potential in cardiac events. Serum was collected from 73 patients with; AMI, stable coronary artery disease (CAD), and controls during cardiac catheterization. Biomarker levels were determined and correlated with clinical data. IL-6 (11.75pg/ml, P<0.05) and sIL-6R (41,340pg/ml, P=0.05) were elevated in AMI compared with CAD and controls. At presentation, hsCRP was elevated in AMI patients (4.69mg/L) compared to controls (2.69mg/L, P<0.05); however, there was a significant decrease in hsCRP between AMI (4.69mg/L) and CAD patients (7.4mg/L, P<0.05). After 24h post-AMI hsCRP levels were increased compared to stable CAD (60.46mg/L, P<0.05) and were preceded by increased IL-6 at presentation. Soluble Gp130 (sGp130) showed no significant change between AMI, CAD, and control patients. However, sGp130 positively correlated with peak troponin in AMI (R=0.587, P<0.01), and negatively correlated with previous AMI (R=-0.382, P<0.05). Circulating monocyte mRNA expression isolated from selected AMI patients showed an increase in IL-6 mRNA (5.28-fold, P<0.01) and a decrease in both IL-6R (0.374-fold, P<0.01) and sGp130 mRNA (0.38-fold, P<0.01) as compared to CAD and controls. Results demonstrate that IL-6 and sIL-6R are associated with AMI and cardiac injury. These data support the hypothesis that trans-IL-6 receptor binding may alter intracellular signaling, and blocking of IL-6 receptor binding may be pathogenic in AMI. These data may be predictive of mechanism(s) by which plaques become unstable and rupture.
Cytokine 04/2013; · 3.02 Impact Factor
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Ryan W Gan,
Kevin D Deane,
Gary O Zerbe,
M Kristen Demoruelle,
Michael H Weisman,
Jane H Buckner,
Peter K Gregersen, Ted R Mikuls,
James R O'Dell,
Richard M Keating,
V Michael Holers,
Jill M Norris
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ABSTRACT: INTRODUCTION: Studies suggest that respiratory exposures including smoking, proximity to traffic and air pollution might be associated with development of rheumatoid arthritis (RA). RA-related autoantibodies are predictive of the development of RA. OBJECTIVE: We evaluated the relationship between RA-related autoantibodies and exposure to particulate matter (PM), a measure of air pollution of interest to health, in individuals without RA. METHODS: The Studies of the Etiology of Rheumatoid Arthritis (SERA) is a multicentre study following first-degree relatives (FDRs) of a proband with RA. FDRs are without the 1987 ACR (American College of Rheumatology) classifiable RA at enrolment and are followed for the development of RA-related autoimmunity. RA-related autoantibody outcomes as well as tender and swollen joint outcomes were assessed. Exposure to PM was assigned using ambient air pollution monitoring data and interpolated with inverse distance weighting spatial analyses using Geographic Information Systems. PM exposures were linked to FDR's residential zip codes. RESULTS: RA-related autoantibodies as well as tender or swollen joints are not associated with ambient PM concentrations. DISCUSSION: While other respiratory exposures may be associated with increased risk of RA, our data suggest that ambient PM is not associated with autoantibodies and joint signs among individuals without RA, but at increased risk of developing RA.
Annals of the rheumatic diseases 04/2013; · 8.11 Impact Factor
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Lisa A Davis,
Grant W Cannon,
Lauren F Pointer,
Leah M Haverhals,
Roger K Wolff, Ted R Mikuls,
Andreas M Reimold,
Gail S Kerr,
J Steuart Richards,
Dannette S Johnson,
Robert Valuck,
Allan Prochazka,
Liron Caplan
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ABSTRACT: OBJECTIVE: C677T and A1298C polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with increased cardiovascular (CV) events in non-rheumatoid arthritis (RA) populations. We investigated potential associations of MTHFR polymorphisms and use of methotrexate (MTX) with time-to-CV event in data from the Veterans Affairs Rheumatoid Arthritis (VARA) registry. METHODS: VARA participants were genotyped for MTHFR polymorphisms. Variables included demographic information, baseline comorbidities, RA duration, autoantibody status, and disease activity. Patients' comorbidities and outcome variables were defined using International Classification of Diseases-9 and Current Procedural Terminology codes. The combined CV event outcome included myocardial infarction (MI), percutaneous coronary intervention, coronary artery bypass graft surgery, and stroke. Cox proportional hazards regression was used to model the time-to-CV event. RESULTS: Data were available for 1047 subjects. Post-enrollment CV events occurred in 97 patients (9.26%). Although there was a trend toward reduced risk of CV events, MTHFR polymorphisms were not significantly associated with time-to-CV event. Time-to-CV event was associated with prior stroke (HR 2.01, 95% CI 1.03-3.90), prior MI (HR 1.70, 95% CI 1.06-2.71), hyperlipidemia (HR 1.57, 95% CI 1.01-2.43), and increased modified Charlson-Deyo index (HR 1.23, 95% CI 1.13-1.34). MTX use (HR 0.66, 95% CI 0.44-0.99) and increasing education (HR 0.87, 95% CI 0.80-0.95) were associated with a lower risk for CV events. CONCLUSION: Although MTHFR polymorphisms were previously associated with CV events in non-RA populations, we found only a trend toward decreased association with CV events in RA. Traditional risk factors conferred substantial CV risk, while MTX use and increasing years of education were protective.
The Journal of Rheumatology 04/2013; · 3.69 Impact Factor
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ABSTRACT: OBJECTIVE: To determine if serum urate concentration is associated with development of hypertension in young adults. METHODS: Retrospective cohort analysis from 4752 participants with available serum urate and without hypertension at baseline from the Coronary Artery Risk Development in Young Adults (CARDIA) study; a mixed race (African-American and White) cohort established in 1985 with 20 years of follow-up data for this analysis. Associations between baseline serum urate concentration and incident hypertension (defined as a blood pressure greater or equal to 140/90 or being on antihypertensive drugs) were investigated in sex-stratified bivariate and multivariable Cox-proportional analyses. RESULTS: Mean age (SD) at baseline was 24.8 (3.6) years for men and 24.9 (3.7) years for women. Compared with the referent category, we found a greater hazard of developing hypertension starting at 345 µmol/l (5.8 mg/dl) of serum urate for men and 214 µmol/l (3.6 mg/dl) for women. There was a 25% increase in the hazard of developing hypertension in men (HR1.25 (95% CI 1.15 to 1.36)) per each mg/dl increase in serum urate but no significant increase in women (HR 1.06 (95%CI 0.97 to 1.16)). CONCLUSIONS: We found a significant independent association between higher serum urate concentrations and the subsequent hazard of incident hypertension, even at concentrations below the conventional hyperuricaemia threshold of 404 µmol/l (6.8 mg/dl).
Annals of the rheumatic diseases 09/2012; · 8.11 Impact Factor
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ABSTRACT: Total shoulder arthroplasty is increasingly used in the treatment of arthritis. However, the effect of total shoulder arthroplasty on health-related quality of life has not been fully established. The goal of this systematic review and meta-analysis was to characterize the change in generic and shoulder-specific health-related quality-of-life measures resulting from total shoulder arthroplasty.
We identified published studies reporting preoperative and postoperative health-related quality-of-life outcomes for patients receiving total shoulder arthroplasty. Health-related quality-of-life measures were identified, and meta-analysis was used to calculate standardized mean differences (SMDs, reflective of the effect size) and 95% confidence intervals for each scale.
Twenty studies (1576 total shoulder replacements) met the inclusion criteria. Outcome measures were analyzed after an average postoperative follow-up duration of 3.7 ± 2.2 years. The Short Form-36 demonstrated significant improvement in physical component summary scores (SMD = 0.7, p < 0.001) but not in mental component summary scores (SMD = 0.2, p = 0.37). Significant improvements were observed in the visual analog scale score for pain (SMD = -2.5, p < 0.001) and scores on three shoulder-specific measures: the Constant score (SMD = 2.7, p < 0.001), American Shoulder and Elbow Surgeons score (SMD = 2.9, p < 0.001), and Simple Shoulder Test (SMD = 2.3, p < 0.001).
Total shoulder arthroplasty leads to significant improvements in scores for function and pain. Shoulder-specific measures of function consistently showed the greatest degree of improvement, with large effect sizes. Total shoulder arthroplasty also leads to significant improvements in overall physical well-being, with a moderate-to-large effect size.
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
The Journal of Bone and Joint Surgery 09/2012; 94(17):e1271-9. · 3.27 Impact Factor
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ABSTRACT: OBJECTIVE: To characterize gout-related emergency department (ED) utilization using a nationally representative sample and to examine factors associated with the frequency and charges of gout-related ED visits. METHODS: Using the National Emergency Department Sample (NEDS) data from 2006 to 2008, the weighted national frequency of gout visits was calculated along with median ED charge and total national ED-related charges. Associations of several patient- and facility-level factors were examined with the occurrence of gout visits using multivariable logistic regression and with ED-related charges using multivariable linear regression. RESULTS: Gout was the primary indication for 168,410 ED visits in 2006, 171,743 visits in 2007, and 174,823 visits in 2008, accounting for ∼0.2% of all visits annually and generating ED charges of more than $128 million in 2006, $ 144 million in 2007, and $166 million in 2008. Age, male gender, household income less than $38,000, private insurance and Medicaid status are associated with an increased propensity for ED utilization in gout. Higher ED-related charges for gout were associated with female gender, age, a higher number of coded diagnoses, and a metropolitan residence. CONCLUSION: Gout accounts for a substantial proportion of ED visits leading to significant healthcare charges. Effective strategies to reduce gout burden in EDs could potentially benefit by targeting groups characterized by factors demonstrated to be related to a higher ED utilization in gout as identified by our study.
Arthritis care & research. 09/2012;
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Jan M Hughes-Austin,
Kevin D Deane,
Lezlie A Derber,
Jason R Kolfenbach,
Gary O Zerbe,
Jeremy Sokolove,
Lauren J Lahey,
Michael H Weisman,
Jane H Buckner, Ted R Mikuls,
James R O'Dell,
Richard M Keating,
Peter K Gregersen,
William H Robinson,
V Michael Holers,
Jill M Norris
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ABSTRACT: OBJECTIVE: We investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with systemic inflammation in a prospective cohort of first-degree relatives (FDRs) of RA probands, a population without RA but at increased risk for its future development. METHODS: We studied 44 autoantibody positive FDRs, of whom 29 were rheumatoid factor (RF) positive, 25 were positive for the high risk autoantibody profile (HRP), that is, positive for anti-cyclic citrullinated peptide and/or for at least two RF IgM, IgG or IgA isotypes, and nine FDRs who were positive for both; and 62 FDRs who were never autoantibody positive. Twenty-five cytokines/chemokines were measured using a bead-based assay in serum. As a comprehensive measure of inflammation, we calculated a Cytokine Score by summing all cytokine/chemokine levels, weighted by their regression coefficients for RA-autoantibody association. We compared C-reactive protein, individual cytokines/chemokines and Cytokine Score to the outcomes: positivity for RF and for the HRP using logistic regression. RESULTS: Adjusting for age, sex, ethnicity and ever smoking, the Cytokine Score and levels of IL-6 and IL-9 were associated with both RF and HRP. IL-2, granulocyte macrophage-colony stimulating factor (GM-CSF), and interferon (IFN)-γ were associated with HRP only. Associations between the Cytokine Score and RF and HRP positivity were replicated in an independent military personnel cohort. CONCLUSIONS: In first-degree relatives of patients with RA, RA-related autoimmunity is associated with inflammation, as evidenced by associations with multiple cytokines and chemokines.
Annals of the rheumatic diseases 08/2012; · 8.11 Impact Factor
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J Steuart Richards,
Grant W Cannon,
Candace L Hayden,
Richard L Amdur,
Deana Lazaro, Ted R Mikuls,
Andreas M Reimold,
Liron Caplan,
Dannette S Johnson,
Pascale Schwab,
Bogdan N Cherascu,
Gail S Kerr
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ABSTRACT: OBJECTIVE: Pharmacy Benefits Management Program (PBM) data for patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry were linked with clinical data to determine bisphosphonate adherence and persistence among U.S. Veterans with RA and determine factors associated with adherence. METHODS: The primary outcome measures were the duration of bisphosphonate therapy and the medication possession ratio (MPR). Patients with a MPR < 0.80 were classified non-adherent. Potential covariates considered in the analysis included patient demographics, RA disease activity and severity parameters, and factors associated with osteoporosis risk. Associations of patient factors with duration of therapy and adherence and were examined using multivariable regression modeling. RESULTS: Bisphosphonates were prescribed to 573 (41.5%) of 1382 VARA subjects. The mean duration of therapy for bisphosphonates was 39.2 (±31.4) months. Longer duration of therapy correlated with older age, a higher level of education and DXA testing. The mean MPR of VARA subjects for bisphosphonate therapy was 0.69 (± 0.28); 302 (52.7%) were non-adherent. In multivariate analyses, non-adherence with bisphosphonate therapy was associated with longer duration of RA (OR 1.02; 95% CI 1.00, 1.04) and duration of bisphosphonate therapy > 32 months (OR 1.63; 95% CI 1.04, 2.57). Caucasians were less likely to have a low MPR compared with non-Caucasians (OR 0.52; 95% CI 0.30, 0.88). CONCLUSIONS: Non-adherence with bisphosphonates was common in this cohort of RA patients and associated with non-Caucasian ethnicity a longer duration of RA and a longer duration of bisphosphonate therapy. © 2012 by the American College of Rheumatology.
Arthritis care & research. 06/2012;
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Ted R Mikuls,
Prasad R Padala,
Harlan R Sayles,
Fang Yu,
Kaleb Michaud,
Liron Caplan,
Gail S Kerr,
Andreas Reimold,
Grant W Cannon,
J Steuart Richards,
Deana Lazaro,
Geoffrey M Thiele,
Joseph A Boscarino
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ABSTRACT: OBJECTIVE: To examine the relationship between posttraumatic stress disorder (PTSD) and disease activity in U.S. veterans with rheumatoid arthritis (RA). METHODS: U.S. veterans with RA were enrolled in a longitudinal observational study and were categorized as having 1) PTSD, 2) other anxiety/depression disorders, or 3) neither of these psychiatric diagnoses using administrative codes. Generalized linear mixed effects models were used to examine the associations of diagnostic groups with outcomes measured over a mean follow-up period of 3.0 years. RESULTS: At enrollment, 1,522 patients had a mean age of 63 years, were primarily men (91%), and a majority (78%) reported Caucasian race. A diagnosis of PTSD was observed in 178 (11.7%) and other anxiety/depression diagnoses (excluding PTSD) were found in 360 (23.7%) patients. Presence of a PTSD diagnosis was independently associated with higher values of self-reported pain, physical impairment, tender joint count, and worse patient global well-being scores compared to patients with no psychiatric diagnosis. There were no significant group differences in swollen joint count, erythrocyte sedimentation rate (ESR), or Disease Activity Score (DAS)-28. There were no differences for any outcomes comparing those with PTSD and those with other anxiety/depression diagnoses. CONCLUSION: In this RA cohort, the diagnosis of PTSD was associated with worse patient-reported outcomes and tender joint counts but not with other physician- or laboratory-based measures of disease activity. These results suggest that PTSD, along with other anxiety / depression disorders, may confound RA disease activity assessments that rely on patient-reported outcomes and resulting treatment decisions. © 2012 by the American College of Rheumatology.
Arthritis care & research. 06/2012;
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Arthritis care & research. 06/2012; 64(10):1623-4.
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Ted R Mikuls,
Geoffrey M Thiele,
Kevin D Deane,
Jeffrey B Payne,
James R O'Dell,
Fang Yu,
Harlan Sayles,
Michael H Weisman,
Peter K Gregersen,
Jane H Buckner,
Richard M Keating,
Lezlie A Derber,
William H Robinson,
V Michael Holers,
Jill M Norris
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ABSTRACT: PURPOSE: To examine the relationship of Porphyromonas gingivalis (Pg) with the presence of autoantibodies in individuals at risk for rheumatoid arthritis (RA). METHODS: Participants included: 1) a cohort enriched with HLA-DR4 and 2) those at risk for RA by virtue of having a first-degree relative with RA. None satisfied 1987 ACR RA classification criteria. Autoantibodies measured included anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF; nephelometry, IgA, IgM, IgG). Individuals were considered autoantibody positive (n = 113) with ≥ 1 positive autoantibody with individuals further categorized as 'high-risk' (n = 38; positive ACPA or ≥ 2 RF assays). Autoantibody negative individuals served as comparators (n = 171). Antibody to Pg, P. intermedia (Pi), and F. nucleatum (Fn) were measured. Associations of bacterial antibodies with group status were examined using logistic regression. RESULTS: Anti-Pg concentrations were higher in high-risk (p = 0.011) and autoantibody positive group (p = 0.010) than in the autoantibody negative group. There were no group differences in anti-Pi or anti-Fn concentrations. After multivariable adjustment, anti-Pg concentrations (but not anti-Pi or anti-Fn) were significantly associated with autoantibody positive and high-risk status (p < 0.05). CONCLUSION: Immunity to Pg, but not Pi or Fn, is significantly associated with the presence of RA-related autoantibodies in individuals at risk for RA. These results support the hypothesis that infection with Pg may play a central role in the early loss of tolerance to self-antigens in RA pathogenesis.
Arthritis & Rheumatism 06/2012; · 7.87 Impact Factor
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ABSTRACT: OBJECTIVE: Cigarette smoking has emerged as a risk factor for development of rheumatoid arthritis (RA). Recent studies have suggested that cigarette smoking may lead to lower treatment response rates with methotrexate (MTX) and some biologic agents in RA. Knowledge of whether tobacco exposure reduces treatment efficacy is important as smoking could represent a modifiable factor in optimizing RA treatment. METHODS: Study participants included patients with early RA (<3 years duration) enrolled in the Treatment of Early Aggressive RA (TEAR) trial, a randomized, blinded, placebo-controlled clinical trial (RCT) comparing early intensive therapy (MTX + etanercept or MTX + hydroxychloroquine + sulfasalazine [triple therapy]) versus initial treatment with MTX with step-up to MTX + etanercept or to triple therapy if still active at 24 weeks. Serum cotinine was measured using a commercially available ELISA at baseline and 48 weeks with detectable concentrations at both visits serving as indicator of smoking status. Mean Disease Activity Score (DAS-28) was compared by smoking status, adjusting for baseline disease activity. RESULTS: Of 412 subjects included in the analysis, 293 (71%) were categorized as 'non-smokers' and 119 (29%) as 'current smokers'. There were no differences in the mean DAS-28 between 48 and 102 weeks based on smoking status for the overall group (p=0.881) or by specific treatment assignment. CONCLUSION: Among patients enrolled in a large RCT of early RA with poor prognostic factors, smoking status did not impact treatment responses for those receiving early combination or initial MTX with step-up therapy at 24 weeks if still active.
Arthritis care & research. 06/2012;
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Liron Caplan,
Lisa A Davis,
Christina M Bright,
Gail S Kerr,
Deana M Lazaro,
Nasim A Khan,
J Steuart Richards,
Dannette S Johnson,
Grant W Cannon,
Andreas M Reimold, Ted R Mikuls
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ABSTRACT: OBJECTIVE: Obesity is a prevalent condition and a serious health concern. The relationship between obesity and RA disease activity and severity has not been adequately examined, and there are concerns that periarticular adipose tissue may reduce the utility of the joint examination. METHODS: We used a cross-sectional study to compare the performance of swollen joint count (SJC) in subjects with rheumatoid arthritis (RA) across body mass index (BMI) strata. Specifically, regression techniques tested for associations of SJC and seven RA disease activity/severity measures (including high sensitivity c-reactive protein, radiographic changes, and multi-dimensional health assessment questionnaire scores) within BMI quartiles. We also evaluated the association of BMI with radiographic evidence of RA in multivariate analyses and the association of BMI with SJC. Clinical and laboratory data from 980 Veterans Affairs Rheumatoid Arthritis (VARA) registry participants were analyzed using linear and logistic regression. RESULTS: Associations were evident between SJC and six of the seven examined RA disease activity/severity measures. SJC predicts RA disease activity/severity at least as well in more obese subjects as in subjects with lower BMIs, and there was a trend towards better performance in higher BMI individuals. Subjects with higher BMIs were marginally less likely to be characterized by radiographic changes (O.R. 0.98, p=0.051). We found no association between BMI and SJC. CONCLUSIONS: BMI does not obscure the relationship of SJC and objective disease activity measures. There is a borderline association of higher BMI and likelihood of radiographic changes characteristic of RA after controlling for clinical characteristics.
Arthritis care & research. 05/2012;
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ABSTRACT: Citrullinated self-proteins are thought to be involved in the onset/progression of rheumatoid arthritis (RA). Numerous studies have been performed to look for the self-antigen that becomes citrullinated and induces RA. Importantly, these studies have been performed using citrullinated self-antigens injected into an animal model in the presence of a strong adjuvant in order to derive the response. However, to date no studies have been performed to determine if these phenotypes can be induced in the absence of an adjuvant.
To investigate this possibility, mice were immunized with citrullinated or non-citrullinated mouse Type II collagen (Cit-Col or Col) in the presence or absence of Freund's Complete Adjuvant (FCA).
An autoimmune-like RA response was observed in mice immunized with Cit-Col in the absence of FCA; by the increase in caliper score, visual observation, and micro-CT analysis of bone erosions. Antibody and T-cell responses were increased in the Cit-Col injected mice to Cit-Col as well as antibody to Anti-Citrullinated Peptide Antigens (ACPA) as determined by a commercially available test kit.
Therefore, the use of citrullinated mouse collagen induces an autoimmune-like RA in the absence of an adjuvant. These data also suggest that citrullinate self-proteins may be potential molecular adjuvants that assist in driving an inflammatory response, that increases the production of PAD in joint tissue, resulting in the citrullination of other self-proteins to exacerbate the disease.
International immunopharmacology 05/2012; 13(4):424-31. · 2.21 Impact Factor
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ABSTRACT: To investigate what factors influence patient global health assessment (PtGlobal), and how those factors and the reliability of PtGlobal affect the rate, reliability, and validity of recently published American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) remission criteria when used in clinical practice.
We examined consecutive patients with RA in clinical practice and identified 77 who met ACR/EULAR joint criteria for remission (≤ 1 swollen joint and ≤ 1 tender joint). We evaluated factors associated with a PtGlobal > 1, because a PtGlobal ≤ 1 defined ACR/EULAR remission in this group of patients who had already met ACR/EULAR joint criteria.
Of the 77 patients examined, only 17 (22.1%) had PtGlobal ≤ 1 and thus fully satisfied ACR/EULAR criteria. A large proportion of patients not in remission by ACR/EULAR criteria had high PtGlobal related to noninflammatory issues, including low back pain, fatigue, and functional limitations, and a number of patients clustered in the range of PtGlobal > 1 and ≤ 2. However, the minimal detectable difference for PtGlobal was 2.3. In addition, compared with a PtGlobal severity score, a PtGlobal activity score was 3.3% less likely to be abnormal (> 1).
Noninflammatory factors contribute to the level of PtGlobal and result in the exclusion of many patients who would otherwise be in "true" remission according to the ACR/EULAR definition. Reliability problems associated with PtGlobal can also result in misclassification, and may explain the observation of low longterm remission rates in RA. As currently constituted, the use of the ACR/EULAR remission criteria in clinical practice appears to be problematic.
The Journal of Rheumatology 05/2012; 39(6):1139-45. · 3.69 Impact Factor
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Ted R Mikuls,
Tricia Levan,
Karen A Gould,
Fang Yu,
Geoffrey M Thiele,
Kimberly K Bynote,
Doyt Conn,
Beth L Jonas,
Leigh F Callahan,
Edwin Smith,
Richard Brasington,
Larry W Moreland,
Richard Reynolds,
Angelo Gaffo,
S Louis Bridges
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ABSTRACT: To examine whether polymorphisms in genes coding for drug-metabolizing enzymes (DMEs) have an impact on rheumatoid arthritis (RA) risk due to cigarette smoking in African Americans.
Smoking status was evaluated in African American patients with RA compared with non-RA controls, with smoking exposure categorized as heavy smoker (≥10 pack-years) versus never smoker/<10 pack-years. Individuals were genotyped for a homozygous deletion polymorphism in the M1 gene loci of glutathione S-transferase (GSTM1-null) in addition to tagging single-nucleotide polymorphisms (SNPs) in N-acetyltransferase 1 (NAT1), NAT2, and epoxide hydrolase 1 (EPXH1). Associations of these genotypes with RA risk were examined using logistic regression, and gene-smoking interactions were assessed.
There were no significant associations of any DME genotype with RA. After adjustment for multiple comparisons, there were significant additive interactions between heavy smoking and the NAT2 SNPs rs9987109 (P(additive) = 0.000003) and rs1208 (P(additive) = 0.00001); the attributable proportion due to interaction ranged from 0.61 to 0.67. None of the multiplicative gene-smoking interactions examined remained significant with regard to overall disease risk, after adjustment for multiple testing. There was no evidence of significant gene-smoking interactions in analyses of GSTM1-null, NAT1, or EPXH1. DME gene-smoking interactions were similar when cases were limited to those patients who were positive for anti-citrullinated protein antibodies.
Among African Americans, RA risk imposed by heavy smoking appears to be mediated in part by genetic variation in NAT2. While further studies are needed to elucidate the mechanisms underpinning these interactions, these SNPs appear to identify African American smokers at a much higher risk for RA, in whom the relative risk is at least 2-fold higher when compared to nonsmokers lacking these risk alleles.
Arthritis & Rheumatism 03/2012; 64(3):655-64. · 7.87 Impact Factor
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ABSTRACT: Findings that African-American race/ethnicity is associated with higher concentrations of serum urate have not been adjusted for possible confounding factors or have not explored this question as a primary outcome. We tested this hypothesis in a bi-racial cohort of younger African-American and white men and women.
Data from 5,049 participants at the Coronary Artery Risk Development in Young Adults (CARDIA) cohort baseline (1985 to 1986) and follow-up for up to 20 years of individuals without hyperuricemia (defined as a serum urate of 6.8 mg/dL or more) at baseline were utilized. We determined associations between race, serum urate and the development of hyperuricemia in sex-specific cross-sectional and longitudinal analyses. Confounding factors examined included: age at enrollment, body mass index, development of hypertension, glomerular filtration rate, medication use, diet and alcohol intake and menopausal symptoms in women.
Referent to whites, African-American men and women had significantly lower concentrations of serum urate at baseline. African-American men had an essentially equal risk of developing incident hyperuricemia during follow-up compared with white men (multivariable adjusted HR = 1.12 (0.88 to 1.40)). African-American women developed a significantly increased risk of hyperuricemia when compared to white women (HR = 2.31 (1.34 to 3.99)).
Young African-American men and women had lower concentrations of serum urate than whites. During longitudinal follow-up, African-American women had a significantly increased risk of developing hyperuricemia when compared with white women, a difference that was not observed in men. Differences in production of serum urate or a more rapid decline in fractional excretion of serum urate are potential, albeit still unproven, explanations for these findings in African-American women.
Arthritis research & therapy 01/2012; 14(1):R4. · 4.27 Impact Factor
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ABSTRACT: Minocycline and doxycycline are safe and moderately effective disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of early, DMARD-naïve rheumatoid arthritis (RA), although little is known about their use outside clinical trials. We characterize the use of minocycline and doxycycline in community-dwelling RA patients by examining associated prescribing patterns, patient-level determinants of use, and side-effect profiles.
We studied 15,716 patients with RA observed between 1998 and 2009 while participating in a long-term US observational study.
Minocycline or doxycycline was prescribed by 18% of rheumatologists (interquartile range one to two patients per physician) to 9% of RA patients. Significant differences between minocycline-treated and doxycycline-treated patients and nontreated patients included age (58.4 years vs. 59.8 years), RA duration (14.8 years vs. 13.7 years), Caucasian race (93.7% vs. 89.7%), lifetime DMARDs and biologics (3.3 vs. 2.5), prednisone use (40.1% vs. 35.3%), and Medical Outcomes Study 36-Item Short Form Survey physical component summary score (35.0 vs. 36.4). In multivariable Cox regression, patients initiating minocycline or doxycycline had increased disease activity, more comorbidities, and a greater number of prior nonbiologic DMARDs. Side effects were reported by 17.8% of minocycline users and 11.8% of doxycycline users. Skin complaints accounted for 54% of minocycline patient-reported side effects. The most commonly effected organ systems for doxycycline were gastrointestinal (35.4%) and skin (33.7%). Approximately 75% of side effects were of mild or moderate severity.
Rheumatologists have not embraced minocycline or doxycycline as primary treatment options for RA and reserve their use primarily in patients with long-standing, refractory disease. These drugs are generally well tolerated, with skin complaints, nausea, and dizziness being the most common patient-reported side effects.
Arthritis research & therapy 10/2011; 13(5):R168. · 4.27 Impact Factor
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Jeffrey R Curtis,
John W Baddley,
Shuo Yang,
Nivedita Patkar,
Lang Chen,
Elizabeth Delzell, Ted R Mikuls,
Kenneth G Saag,
Jasvinder Singh,
Monika Safford,
Grant W Cannon
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ABSTRACT: Administrative claims data have not commonly been used to study the clinical effectiveness of medications for rheumatoid arthritis (RA) because of the lack of a validated algorithm for this outcome. We created and tested a claims-based algorithm to serve as a proxy for the clinical effectiveness of RA medications.
We linked Veterans Health Administration (VHA) medical and pharmacy claims for RA patients participating in the longitudinal Department of Veterans Affairs (VA) RA registry (VARA). Among individuals for whom treatment with a new biologic agent or nonbiologic disease-modifying agent in rheumatic disease (DMARD) was being initiated and with registry follow-up at 1 year, VARA and administrative data were used to create a gold standard for the claims-based effectiveness algorithm. The gold standard outcome was low disease activity (LDA) (Disease Activity Score using 28 joint counts (DAS28) ≤ 3.2) or improvement in DAS28 by > 1.2 units at 12 ± 2 months, with high adherence to therapy. The claims-based effectiveness algorithm incorporated biologic dose escalation or switching, addition of new disease-modifying agents, increase in oral glucocorticoid use and dose as well as parenteral glucocorticoid injections.
Among 1,397 patients, we identified 305 eligible biologic or DMARD treatment episodes in 269 unique individuals. The patients were primarily men (94%) with a mean (± SD) age of 62 ± 10 years. At 1 year, 27% of treatment episodes achieved the effectiveness gold standard. The performance characteristics of the effectiveness algorithm were as follows: positive predictive value, 76% (95% confidence interval (95% CI) = 71% to 81%); negative predictive value, 90% (95% CI = 88% to 92%); sensitivity, 72% (95% CI = 67% to 77%); and specificity, 91% (95% CI = 89% to 93%).
Administrative claims data may be useful in evaluating the effectiveness of medications for RA. Further validation of this effectiveness algorithm will be useful in assessing its generalizability and performance in other populations.
Arthritis research & therapy 09/2011; 13(5):R155. · 4.27 Impact Factor
