James R O'Dell

University of Nebraska at Omaha, Omaha, Nebraska, United States

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Publications (98)745.28 Total impact

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    ABSTRACT: Objective: As a product of oxidative stress associated with tolerance loss in other disease states, we investigated the presence of malondialdehyde-acetaldehyde (MAA) adducts and circulating anti-MAA antibody in rheumatoid arthritis (RA). Methods: Synovial tissues from RA and osteoarthritis patients were examined for the presence of MAA-modified and citrullinated proteins. Anti-MAA antibody isotypes were measured in RA cases (n = 1720) and healthy controls (n = 80) by ELISA. Antigen-specific anti-citrullinated protein antibody (ACPA) was measured in RA cases using a multiplex antigen array. Anti-MAA isotype concentrations were compared in a subset of cases (n = 80) and matched controls (n = 80). Associations of anti-MAA antibody isotypes with disease characteristics, including ACPA, were examined in all RA cases.Results: MAA adducts were increased in RA synovial tissues relative to osteoarthritis and co-localized with citrullinated protein. Anti-MAA antibody isotypes were increased in RA cases vs. controls (p < 0.001). Among RA cases, anti-MAA antibody isotypes were associated with ACPA and RF positivity (p < 0.001) in addition to select measures of disease activity. Higher anti-MAA antibody concentrations were associated with a higher number of positive antigen-specific ACPA analytes in high titer (p < 0.001) and a higher ACPA score (p < 0.001) independent of other covariates.Conclusion: MAA adduct formation is increased in RA and appears to result in robust antibody responses that are strongly associated with ACPA. These results support speculation that MAA formation may be a co-factor that drives tolerance loss resulting in the autoimmune responses characteristic of RA. This article is protected by copyright. All rights reserved.
    03/2015; 67(3):645-655. DOI:10.1002/art.38969
  • Manpreet K Sethi, James R O'Dell
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    ABSTRACT: Dramatic improvement seen in the prognosis of rheumatoid arthritis has been driven by higher expectations, led by newer drugs and more intensive use of the older drugs. Although methotrexate has retained its place as the first-line agent, there has been great interest in comparing biologicals to conventional Disease Modifying Anti Rheumatic Drugs (DMARDs) over the past few years with the updated guidelines from both the American College of Rheumatology and European League Against Rheumatism. We have tried to critically summarize the findings of some landmark trials that compare these two approaches. Treatment of Early Rheumatoid Arthritis, The Swedish Pharmacotherapy study and Rheumatoid Arthritis Comparison of Active Therapies are landmark trials that were designed to compare strategies using biologicals vs. conventional DMARDs. We will review the safety and efficacy data from these three trials here and also briefly the important cost differential. Methotrexate should be the first-line therapy for most rheumatoid arthritis patients and will produce the desired results in greater than one-third of the patients. When methotrexate is not adequate, triple DMARD therapy should be added which will result in control of approximately another one-third of the patients. Ultimately, and usually before 1 year of disease, the remainder of patients will require biological therapies usually added to conventional DMARDs. There is no evidence that this step-up approach results in any long-term disadvantage and good evidence that it results in substantial cost savings.
    Current Opinion in Rheumatology 01/2015; 27(2). DOI:10.1097/BOR.0000000000000153 · 5.07 Impact Factor
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    ABSTRACT: Objective: To evaluate the effect of sustained ACR/EULAR Boolean remission on residual joint inflammation assessed by magnetic resonance imaging (MRI) and to secondarily evaluate other clinical definitions of remission, within an early seropositive rheumatoid arthritis (RA) cohort.Methods: A subcohort of 118 RA patients were enrolled from patients who completed the two-year double-blind randomized Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. Patients received a single contrast enhanced 1.5 Tesla MRI of their most involved wrist. Two readers scored MRI for synovitis, osteitis, tenosynovitis, and erosions. Clinical assessments were performed every three months during the trial and at time of MRI.Results: The subcohort was 92% seropositive with mean age 51 years, duration 4.1 months, and DAS28-ESR 5.8 at TEAR entry. Total MRI Inflammatory Scores (tenosynovitis+synovitis+osteitis) were lower among patients in clinical remission. Lower MRI scores were correlated with longer duration of CDAI remission (rho=0.22, p=0.03). At the time of MRI, 89 patients had no wrist pain/tenderness/swelling; however, all 118 patients had MRI evidence of residual joint inflammation after two years. No statistically significant differences in damage or MRI inflammatory scores were observed across treatment groups.Conclusion: This is the first detailed appraisal describing the relationship between clinical remission cut-points and MRI inflammatory scores within a RA RCT. The most stringent remission criteria (2011 ACR/EULAR and CDAI) best differentiate the total MRI inflammatory scores. These results document that 2-years of triple therapy or TNF+methotrexate treatment in early RA does not eliminate MRI evidence of joint inflammation. This article is protected by copyright. All rights reserved.
    12/2014; DOI:10.1002/acr.22541
  • Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):139-139. DOI:10.1136/annrheumdis-2014-eular.1954 · 9.27 Impact Factor
  • Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):393-394. DOI:10.1136/annrheumdis-2014-eular.2057 · 9.27 Impact Factor
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    ABSTRACT: To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA. Patients with RA (n = 287) and patients with osteoarthritis as disease controls (n = 330) underwent a standardized periodontal examination. The HLA-DRB1 status of all participants was imputed using single-nucleotide polymorphisms from the extended major histocompatibility complex. Circulating anti-P gingivalis antibodies were measured using an enzyme-linked immunosorbent assay, and subgingival plaque was assessed for the presence of P gingivalis using polymerase chain reaction (PCR). Associations of PD with RA were examined using multivariable regression. Presence of PD was more common in patients with RA and patients with anti-citrullinated protein antibody (ACPA)-positive RA (n = 240; determined using the anti-cyclic citrullinated peptide 2 [anti-CCP-2] test) than in controls (35% and 37%, respectively, versus 26%; P = 0.022 and P = 0.006, respectively). There were no differences between RA patients and controls in the levels of anti-P gingivalis or the frequency of P gingivalis positivity by PCR. The anti-P gingivalis findings showed a weak, but statistically significant, association with the findings for both anti-CCP-2 (r = 0.14, P = 0.022) and rheumatoid factor (RF) (r = 0.19, P = 0.001). Presence of PD was associated with increased swollen joint counts (P = 0.004), greater disease activity according to the 28-joint Disease Activity Score using C-reactive protein level (P = 0.045), and higher total Sharp scores of radiographic damage (P = 0.015), as well as with the presence and levels of anti-CCP-2 (P = 0.011) and RF (P < 0.001). The expression levels of select ACPAs (including antibodies to citrullinated filaggrin) were higher in patients with subgingival P gingivalis and in those with higher levels of anti-P gingivalis antibodies, irrespective of smoking status. Associations of PD with established seropositive RA were independent of all covariates examined, including evidence of P gingivalis infection. Both PD and P gingivalis appear to shape the autoreactivity of RA. In addition, these results demonstrate an independent relationship between PD and established seropositive RA.
    05/2014; 66(5):1090-1100. DOI:10.1002/art.38348
  • Annals of the Rheumatic Diseases 01/2014; 72(Suppl 3):A240-A240. DOI:10.1136/annrheumdis-2013-eular.752 · 9.27 Impact Factor
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    ABSTRACT: Joint damage in rheumatoid arthritis (RA) is characterized by cartilage and bone loss resulting in pain, deformity, and loss of joint function. Anti-citrullinated protein antibody (ACPA) has been implicated in RA pathogenesis and predicts radiographical joint damage and clinical severity. Therefore, the purpose of this study was to assess bone loss by micro-CT, histological joint damage, and ACPA levels using a mouse model of RA. Arthritis was induced by immunizing DBA/1 mice with autologous citrullinated type II mouse collagen (CIT-CII) weekly for 4 weeks. Mice immunized with autologous CII served as controls. At week 5, mice were killed, ACPA levels determined, and micro-CT performed to quantitatively analyze bone damage. Micro-CT analysis revealed significant loss of bone density, volume, and surface (p < 0.05) in bone peripheral to the inflamed joints of CIT-CII animals compared to CII controls. Histological staining demonstrated cartilage, proteoglycan, joint collagen, and bone collagen loss in the CIT-CII group compared to CII. Serum ACPA levels were increased (p = 0.03) in the CIT-CII group compared to CII, and these levels were inversely correlated with bone quantity and quality. In this study, we demonstrate that immunization with autologous CIT-CII initiates significant systemic bone and articular cartilage loss in the absence of adjuvant. Significant inverse correlations of circulating ACPA and bone quality/quantity were present. ACPA levels predict the adverse bone morphological changes in this model of early RA.
    Immunologic Research 12/2013; 58(1). DOI:10.1007/s12026-013-8479-7 · 3.53 Impact Factor
  • Annals of the rheumatic diseases 11/2013; DOI:10.1136/annrheumdis-2013-204263 · 9.27 Impact Factor
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    ABSTRACT: Objective To compare the diagnostic accuracy and agreement of commonly available assays for anti–citrullinated protein antibodies in patients with established rheumatoid arthritis (RA) and subjects at increased risk of RA. Methods Tests for anti–cyclic citrullinated peptide (anti-CCP) antibodies were performed using CCP2 IgG and CCP3.1 IgA/IgG enzyme-linked immunosorbent assays in the following groups: probands with established RA (n = 340) from the Studies of the Etiology of Rheumatoid Arthritis (SERA) cohort and their first-degree relatives (FDRs) without inflammatory arthritis (n = 681), Department of Defense Serum Repository (DoDSR) RA cases with pre–RA diagnosis samples (n = 83; 47 cases also had post–RA diagnosis samples), and blood donor and DoDSR control subjects (n = 283). ResultsIn patients with established RA, the CCP2 assay was more specific (99.2% versus 93.1%; P < 0.01) but less sensitive (58.7% versus 67.4%; P = 0.01) than the CCP3.1 assay; the specificity of the CCP3.1 assay increased to 97.2% when cutoff levels ≥3-fold the standard level were considered. In all subjects, CCP3.1 assay positivity (using standard cutoff levels) was more prevalent. Among DoDSR cases, the CCP2 assay was more specific than the CCP3.1 for predicting a future diagnosis of RA, and higher CCP levels trended toward increasing specificity for the development of RA within 2 years. At standard cutoff levels, assay agreement was good in patients with established RA (κ = 0.76) but poor in FDRs without inflammatory arthritis (κ = 0.25). Conclusion Anti-CCP assays differ to an extent that may be meaningful for diagnosing RA in patients with inflammatory arthritis and evaluating the natural history of RA development in subjects at risk of RA. The mechanisms underlying these differences in test performance need further investigation.
    Arthritis & Rheumatology 09/2013; 65(9). DOI:10.1002/art.38017 · 7.87 Impact Factor
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    ABSTRACT: Objective Methotrexate (MTX) taken as monotherapy is recommended as the initial disease-modifying antirheumatic drug for rheumatoid arthritis (RA). The purpose of this study was to examine outcomes of a blinded trial of initial MTX monotherapy with the option to step-up to combination therapy as compared to immediate combination therapy in patients with early, poor-prognosis RA. Methods In the Treatment of Early Rheumatoid Arthritis (TEAR) trial, 755 participants with early, poor-prognosis RA were randomized to receive MTX monotherapy or combination therapy (MTX plus etanercept or MTX plus sulfasalazine plus hydroxychloroquine). Participants randomized to receive MTX monotherapy stepped-up to combination therapy at 24 weeks if the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) was ≥3.2. ResultsAttrition at 24 weeks was similar in the MTX monotherapy and combination groups. Of the 370 evaluable participants in the initial MTX group, 28% achieved low levels of disease activity and did not step-up to combination therapy (MTX monotherapy group). The mean ± SD DAS28-ESR in participants continuing to take MTX monotherapy at week 102 was 2.7 ± 1.2, which is similar to that in participants who were randomized to immediate combination therapy (2.9 ± 1.2). Participants who received MTX monotherapy had less radiographic progression at week 102 as compared to those who received immediate combination therapy (mean ± SD change in modified Sharp score 0.2 ± 1.1 versus 1.1 ± 6.4). Participants assigned to initial MTX who required step-up to combination therapy at 24 weeks (72%) demonstrated similar DAS28-ESR values (3.5 ± 1.3 versus 3.2 ± 1.3 at week 48) and radiographic progression (change in modified Sharp score 1.2 ± 4.1 versus 1.1 ± 6.4 at week 102) as those assigned to immediate combination therapy. The results for either of the immediate combination approaches, whether triple therapy or MTX plus etanercept, were similar. Conclusion These results in patients with early, poor prognosis RA validate the strategy of starting with MTX monotherapy. This study is the first to demonstrate in a blinded trial that initial MTX monotherapy with the option to step-up to combination therapy results in similar outcomes to immediate combination therapy. Approximately 30% of patients will not need combination therapy, and the 70% who will need it are clinically and radiographically indistinguishable from those who were randomized to receive immediate combination therapy.
    Arthritis & Rheumatology 08/2013; 65(8). DOI:10.1002/art.38012 · 7.87 Impact Factor
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    ABSTRACT: Objective: Examine anti-citrullinated protein/peptide antibodies (ACPA) reactivity and determine associations between ACPA and other rheumatoid arthritis (RA)-related autoantibodies and clinically-assessed swollen or tender joints in first-degree relatives (FDRs) without 1987 and 2010 American College of Rheumatology classified RA. Methods: A bead-based assay measured 16 separate ACPA in sera from 111 FDRs (Ab+) who were positive on at least one visit for any of 5 RA-related autoantibodies (RF, anti-CCP2, and RF isotypes), and 99 FDRs (Ab-) who were never autoantibody positive. Cut-offs for positivity for each ACPA were determined using receiver operating characteristic curves of data from 200 RA cases and 98 blood-bank controls, wherein positivity for ≥ 9 ACPA had 92% specificity and 62% sensitivity for RA. In FDRs, we assessed ACPA reactivity and examined associations between ACPA (number positive and positivity for ≥ 9 ACPA) and RA-related characteristics. Results: Four of 7 anti-CCP2 positive and 8% of anti-CCP2 negative FDRs were positive for ≥ 9 ACPA. After adjusting for age, gender, ethnicity and pack-years of smoking, increasing number of ACPA was directly associated with having ≥ 1 tender joint on exam (OR=1.18, 95% CI 1.04-1.34), with the greatest risk seen in FDRs positive for ≥ 9 ACPA (OR=5.00, 95% CI 1.37-18.18). Conclusions: RA-free FDRs demonstrate reactivity to multiple ACPA, even in those negative for rheumatoid factor and anti-CCP2, and increasing ACPA may be associated with signs of joint inflammation. Prospective evaluation of the relationship between these findings and progression of classifiable RA is warranted. © 2013 American College of Rheumatology.
    Arthritis & Rheumatology 08/2013; 65(8). DOI:10.1002/art.38022 · 7.87 Impact Factor
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    ABSTRACT: Background Few blinded trials have compared conventional therapy consisting of a combination of disease-modifying antirheumatic drugs with biologic agents in patients with rheumatoid arthritis who have active disease despite treatment with methotrexate - a common scenario in the management of rheumatoid arthritis. Methods We conducted a 48-week, double-blind, noninferiority trial in which we randomly assigned 353 participants with rheumatoid arthritis who had active disease despite methotrexate therapy to a triple regimen of disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, and hydroxychloroquine) or etanercept plus methotrexate. Patients who did not have an improvement at 24 weeks according to a prespecified threshold were switched in a blinded fashion to the other therapy. The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28, with scores ranging from 2 to 10 and higher scores indicating more disease activity) at week 48. Results Both groups had significant improvement over the course of the first 24 weeks (P=0.001 for the comparison with baseline). A total of 27% of participants in each group required a switch in treatment at 24 weeks. Participants in both groups who switched therapies had improvement after switching (P<0.001), and the response after switching did not differ significantly between the two groups (P=0.08). The change between baseline and 48 weeks in the DAS28 was similar in the two groups (-2.1 with triple therapy and -2.3 with etanercept and methotrexate, P=0.26); triple therapy was noninferior to etanercept and methotrexate, since the 95% upper confidence limit of 0.41 for the difference in change in DAS28 was below the margin for noninferiority of 0.6 (P=0.002). There were no significant between-group differences in secondary outcomes, including radiographic progression, pain, and health-related quality of life, or in major adverse events associated with the medications. Conclusions With respect to clinical benefit, triple therapy, with sulfasalazine and hydroxychloroquine added to methotrexate, was noninferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy. (Funded by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and others; CSP 551 RACAT ClinicalTrials.gov number, NCT00405275 .).
    New England Journal of Medicine 06/2013; 369(4). DOI:10.1056/NEJMoa1303006 · 54.42 Impact Factor
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    ABSTRACT: OBJECTIVE: To study changes in lipid profiles at 24 weeks among early rheumatoid arthritis (RA) patients participating in the Treatment of Early Rheumatoid Arthritis (TEAR) Trial randomized to initiate methotrexate plus etanercept (MTX+ETA), triple therapy (TT) [MTX plus sulfasalazine plus hydroxychloroquine] or aggressively-titrated MTX monotherapy. METHODS: The TEAR biorepository study had 459 participating patients. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured in serum plasma at 0 and 24 weeks. RESULTS: At 24 weeks, there were statistically significant mean increases in cholesterol levels in the MTX + ETA, TT, and MTX monotherapy arms, the observed increases were 31.4, 28.7 and 30 mg/dL in LDL-C; 19.3, 22.3 and 20.6 mg/dL in HDL-C and 56.8, 53 and 57.3 mg/dL values in TC (p < 0.001 all compared to baseline). There was a statistically significant decrease in TC/HDL-C ratio at 24 weeks in all 3 treatment groups from baseline. There was no difference in any lipid changes between the 3 treatment arms. After multivariable adjustment, change in C-reactive protein was associated with change in LDL-C (p=0.03), HDL-C (p=0.09), and TC (p=0.01), but disease activity score in 28-joints was not. Baseline glucocorticoid use was associated with changes in HDL-C (p=0.03) and TC (p=0.02). CONCLUSION: Levels of TC, LDL-C, and HDL-C increased equivalently shortly after initiation of MTX + ETA, TT and MTX monotherapy among early RA patients with active disease participating in a clinical trial. The clinical relevance of short term changes in traditional lipids on cardiovascular outcomes remains to be determined. © 2013 American College of Rheumatology.
    Arthritis & Rheumatology 06/2013; DOI:10.1002/art.37916 · 7.87 Impact Factor
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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; 40(5). DOI:10.3899/jrheum.120715 · 3.17 Impact Factor
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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; DOI:10.1136/annrheumdis-2012-202949 · 9.27 Impact Factor
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    ABSTRACT: Methotrexate (MTX) has emerged as first-line therapy for early moderate-to-severe rheumatoid arthritis (RA), but individual variation in treatment response remains unexplained. We tested the associations between 863 known pharmacogenetic variants and MTX response in 471 Treatment of Early Aggressive Rheumatoid Arthritis Trial participants with early RA. Efficacy and toxicity were modeled using multiple regression, adjusted for demographic and clinical covariates. Penalized regression models were used to test joint associations of markers and/or covariates with the outcomes. The strongest genetic associations with efficacy were in CHST11 (five markers with P<0.003), encoding carbohydrate (chondroitin 4) sulfotransferase 11. Top markers associated with MTX toxicity were in the cytochrome p450 genes CYP20A1 and CYP39A1, solute carrier genes SLC22A2 and SLC7A7, and the mitochondrial aldehyde dehydrogenase gene ALDH2. The selected markers explained a consistently higher proportion of variation in toxicity than efficacy. These findings could inform future development of personalized therapeutic approaches.The Pharmacogenomics Journal advance online publication, 2 April 2013; doi:10.1038/tpj.2013.11.
    The Pharmacogenomics Journal 04/2013; 14(1). DOI:10.1038/tpj.2013.11 · 5.51 Impact Factor
  • James R. O'Dell
    Arthritis & Rheumatology 04/2013; 65(4). DOI:10.1002/art.37855 · 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.
    12/2012; 64(12). DOI:10.1002/acr.21758
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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 & Rheumatology 11/2012; 64(11). DOI:10.1002/art.34595 · 7.87 Impact Factor

Publication Stats

4k Citations
745.28 Total Impact Points

Institutions

  • 2004–2014
    • University of Nebraska at Omaha
      • Department of Internal Medicine
      Omaha, Nebraska, United States
  • 1991–2014
    • University of Nebraska Medical Center
      • • Division of Rheumatology and Immunology
      • • Department of Internal Medicine
      Omaha, Nebraska, United States
  • 2010–2012
    • The Nebraska Medical Center
      Omaha, Nebraska, United States
    • Albany Medical College
      Albany, New York, United States
  • 2008
    • University of California, Los Angeles
      Los Ángeles, California, United States
  • 2003
    • University of Utah
      • Division of Rheumatology
      Salt Lake City, UT, United States
  • 2001
    • Arthritis Research Center Foundation
      Wichita, Kansas, United States