James R O'Dell

The Nebraska Medical Center, Omaha, Nebraska, United States

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Publications (136)

  • Amy C. Cannella · James R. O'Dell
    Chapter · Jan 2017
  • Gary S. Firestein · Ralph C. Budd · Sherine E. Gabriel · [...] · James R. O'Dell
    Chapter · Jan 2017
  • James R. O'Dell
    Chapter · Jan 2017
  • Melanie K Rohr · Ted R Mikuls · Stanley B Cohen · [...] · James R O'Dell
    [Show abstract] [Hide abstract] ABSTRACT: Objective: Methotrexate (MTX) is the anchor drug in the treatment of rheumatoid arthritis (RA) due to its effectiveness, tolerability, and cost. This study examines MTX prescribing practices in the US from 2009 to 2014. Methods: Symphony Health Solutions which covers 274 million patients in the US was used to identify patients diagnosed with RA who were naïve to MTX in 2009 and 2012. Data was collected including medication use and doses, demographics, and medical co-morbidities. Results: In patients who had five year follow up data available oral (PO) MTX was started in 35,640 in 2009 and 44% remained on this during the follow-up. Of the 20,041 patients who changed therapy during the study period 87% had the addition of or switch to a biologic, while 13% were changed from PO to subcutaneous (SC) MTX. The mean PO dose prior to the start of a biologic was 15.3 mg/week +/- 5 mg. Comparison of 2009 to 2012 showed a modest increase in the mean dose of PO MTX from 15.3 mg to 15.9 mg/week and a small but statistically significant (p < 0.0001) increase in the use of SC MTX after failure of PO MTX from 13% to 16% of patients. Conclusion: MTX is underutilized in the treatment of RA with suboptimal dosing, inadequate duration of therapy, and failure to use subcutaneous administration. Comparison of MTX use between the 2009 and the 2012 cohorts demonstrate only a marginal increase in the dose of PO MTX and the use of SC MTX. This article is protected by copyright. All rights reserved.
    Article · Nov 2016
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    File available · Data · Jul 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: Abnormal function of high density lipoprotein (HDL) has been implicated as a potential mechanism for the increased cardiovascular disease (CVD) in patients with rheumatoid arthritis. The current work evaluated changes in HDL function and HDL-associated proteins over two years of follow-up in early RA patients receiving either methotrexate (MTX) monotherapy or combination therapies in the Treatment of Early Rheumatoid Arthritis (TEAR) trial. Methods: The anti-oxidant capacity of HDL, paraoxonase 1 (PON-1) activity, HDL-associated haptoglobin (HDL-Hp), HDL-associated apolipoprotein AI (HDL-apoA-I), and myeloperoxidase (MPO) levels were measured in 550 TEAR participants at 4 time points (0 [pre-treatment], 24, 48, and 102 weeks). Repeated measures analysis was performed using mixed effect linear models with autoregressive covariate structure to model the within-subject covariance over time. Results: Mixed effect models controlling for traditional CV risk factors, treatment regimen, prednisone use, and statin use demonstrated significant associations of RA disease activity measured by the disease activity score with 28 joint count (DAS28), erythrocyte sedimentation rate (ESR), or C-reactive protein (CRP) with the HDL function profile over time. Specifically, decreases in RA disease activity over time were associated with increases in PON1 activity and HDL-apoA-I levels, and decreases in the HDL inflammatory index (HII), MPO, and HDL-Hp. Conclusion: Decreases in disease activity in early RA patients treated with MTX, MTX + etanercept, or triple therapy in the TEAR trial were associated with improvements in the HDL function profile. Additional work is warranted to evaluate abnormal HDL function as a potential mechanism and therapeutic target for CV risk in patients with RA. This article is protected by copyright. All rights reserved.
    Article · Jul 2016 · Arthritis and Rheumatology
  • J.R. O'Dell · S. Cohen · C. Thorne · T.R. Mikuls
    [Show abstract] [Hide abstract] ABSTRACT: Background European and US guidelines recommend MTX as part of initial treatment for patients with RA.1,2 Biologic agents are recommended for patients with poor prognostic indicators and those who fail to achieve treatment goals after 3–6 months of conventional therapy.1,2 Currently, it is not clear how closely these recommendations are being followed in the US. Objectives To assess patterns of treatment for patients who initiated DMARD treatment in the US in either 2009 or 2012 and were followed for at least 2 years. Methods The analysis used Symphony Health Solutions' anonymized patient-level claims data which captures ∼274 million US patients. Analysis included RA patients identified by ICD-9 codes 714.0 and 714.30 who initiated treatment with either oral MTX or a biologic therapy in 2009 or in 2012 and were followed for 2 years. Information obtained included: demographic characteristics, initial treatments, switches from oral to subcutaneous (SC) MTX and/or biologics (with or without concomitant MTX), timing of treatment changes, and oral MTX or SC MTX dosing at the times of switches/additions or end of follow-up. Results The study included 48,910 patients who initiated treatment in 2009 and 107,636 who started treatment in 2012 (Table). For the RA patients who started treatment in 2009, 27.1% initiated therapy with a biologic and 72.9% started on oral MTX. The respective values for patients initiating therapy in 2012 were 35.6% and 64.4%. Over the first 2 years of follow-up, 35.2% of patients who started MTX in 2009 and 21.6% of those started on MTX in 2012 switched to a biologic or had one added to MTX. A small percentage of patients in each cohort switched from oral to SC MTX. The median duration of oral MTX treatment prior to switching to or adding a biologic was 60 days for patients who initiated treatment in 2009 and 177 days for those who initiated MTX in 2012. View this table: • In this window • In a new window Table 1 Conclusions In the US, a large percentage of RA patients receive a biologic without a prior trial of MTX and this approach to treatment increased from 2009 to 2012. While there is a trend toward underuse of MTX as initial treatment from 2009 to 2012, a higher percentage of patients who started MTX in 2012 remained on this treatment for at least 2 years vs those started in 2009. This suggests many clinicians may not be following best practice with regard to the use of SC MTX. • Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73:492–509. • Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68:1–26. Acknowledgement Study sponsored by Medac Pharma, Inc. Disclosure of Interest J. O'Dell: None declared, S. Cohen Grant/research support from: Abbvie, Amgen, Astellas, Medac, Pfizer, UCB, C. Thorne Grant/research support from: Abbive, Amgen, Celgene, CaREBiodam, Lilly, Novartis, Pfizer, Sanofi, UCB, Consultant for: Abbvie, Centocor, Genzyme, Hospira, Medexus, Pfizer, Paid instructor for: Abbvie, Centocor, Genzyme, Hospira, Medexus/Medac, Pfizer, T. Mikuls Grant/research support from: Roche/Genentech, Consultant for: Pfizer
    Article · Jun 2016 · Annals of the Rheumatic Diseases
  • [Show abstract] [Hide abstract] ABSTRACT: Objectives Previously, we found that omega-3 fatty acids (n-3 FAs) were inversely associated with anti-cyclic citrullinated peptide (anti-CCP) positivity in participants at risk for future rheumatoid arthritis (RA). We investigated whether n-3 FAs were also associated with rheumatoid factor (RF) positivity and whether these associations were modified by shared epitope (SE) positivity. Methods The Studies of the Etiology of RA (SERA) cohort includes RA-free participants who are at increased risk for RA. We conducted a nested case–control study (n=136) to determine the association between RF and anti-CCP2 positivity and n-3 FA percentage in erythrocyte membranes (n-3 FA% in red blood cells (RBCs)). Additionally, in the baseline visit of the SERA cohort (n=2166), we evaluated the association between reported n-3 FA supplement use and prevalence of RF and anti-CCP2. We assessed SE positivity as an effect modifier. Results In the case–control study, increasing n-3 FA% in RBCs was inversely associated with RF positivity in SE-positive participants (OR 0.27, 95% CI 0.10 to 0.79), but not SE-negative participants. Similar associations were seen with anti-CCP positivity in SE-positive participants (OR 0.42, 95% CI 0.20 to 0.89), but not SE-negative participants. In the SERA cohort at baseline, n-3 FA supplement use was associated with a lower prevalence of RF positivity in SE-positive participants (OR 0.32, 95% CI 0.12 to 0.82), but not SE-negative participants; similar but non-significant trends were observed with anti-CCP2. Conclusions The potential protective effect of n-3 FAs on RA-related autoimmunity may be most pronounced in those who exhibit HLA class II genetic susceptibility to RA.
    Article · May 2016 · Annals of the Rheumatic Diseases
  • Hawre Jalal · James R O'Dell · S Louis Bridges · [...] · Kaleb Michaud
    [Show abstract] [Hide abstract] ABSTRACT: Objectives: To evaluate the cost-effectiveness of all 4 interventions in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) clinical trial: Immediate triple (IT), immediate etanercept (IE), step-up triple (ST), and step-up etanercept (SE). Step-up interventions started methotrexate and added either etanercept or sulfasalazine plus hydroxychloroquine to patients with persistent disease activity. Methods: We built a Markov cohort model that uses individual-level data from the TEAR trial, published literature, and supplemental clinical data. Costs were in US$, benefits in quality adjusted life years (QALYs), perspective was societal, and the time horizon was 5 years. Results: The immediate strategies were more efficacious than step-up strategies. SE and IE were more costly than ST and IT primarily due to treatment cost differences. In addition, IT was the least expensive and most effective strategy when the time horizon was 1 and 2 years. When the time horizon was 5 years, IE was marginally more effective than IT (3.483 vs. 3.476 QALYs), but IE was substantially more expensive than IT ($148,800 vs. $52,600), producing an incremental cost-effectiveness ratio (ICER) of $12.5M/QALY. These results were robust to both one-way deterministic and joint probabilistic sensitivity analyses. Conclusions: IT was highly cost-effective in the majority of scenarios. Although IE was more effective in five years, a substantial reduction in the cost of biologics was required in order for IE to become cost-effective in early aggressive RA under willingness-to-pay thresholds that most healthcare settings may find acceptable. This article is protected by copyright. All rights reserved.
    Article · Mar 2016
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    [Show abstract] [Hide abstract] ABSTRACT: Objective: To examine whether genetic, environmental, and serologic rheumatoid arthritis (RA) risk factors are associated with inflammatory joint signs (IJS) in a cohort of RA first-degree relatives (FDRs). Methods: We evaluated RA risk factors and IJS in a prospective cohort of FDRs without RA in the Studies of the Etiology of RA. Genetic factors included five HLA-DRB1 shared epitope alleles and 45 RA-associated single nucleotide polymorphisms; loci were combined using genetic risk scores (GRS) weighted by RA risk. Environmental factors (smoking, body mass index, education, and parity) and RA-related autoantibodies were assessed at baseline. Physical examination at baseline and two-year follow-up by observers blinded to autoantibody status assessed IJS as tender or swollen joints at sites typical for RA. Logistic regression was performed to evaluate associations of genetic, environmental, and serologic factors with IJS. Results: We analyzed 966 non-Hispanic white FDRs at baseline and 262 at two-year follow-up after excluding those with IJS at baseline. Mean age was 47.2 years (SD 15.5), 71% were female, and 55% were shared epitope-positive. Smoking >10 pack-years was associated with IJS at baseline (OR 1.59, 95%CI 1.09-2.32) and at 2 years (OR 2.66, 95%CI 1.01-7.03), compared to never smokers. Smoking and age significantly interacted for risk of IJS (p=0.02). FDRs aged <50 years with >10 pack-years had the highest risk of IJS (OR 4.39, 95%CI 2.22-8.66) compared to never smokers aged <50 years). Conclusion: In a high-risk cohort of FDRs, smoking and age were associated with both prevalent and incident IJS at sites typical for RA. Further prospective investigations of the factors affecting the transitions between pre-clinical RA phases are warranted. This article is protected by copyright. All rights reserved.
    Full-text available · Article · Feb 2016 · Arthritis and Rheumatology
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: To evaluate long term changes in cholesterol levels in early rheumatoid arthritis (RA) patients randomized to initiate methotrexate (MTX) monotherapy, methotrexate + etanercept (MTX+ETA), or triple therapy (TT) [MTX + sulfasalazine (SSZ) + hydroxychloroquine (HCQ)] in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. Methods: Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were analyzed in 416 patients participating in the TEAR trial over 102 weeks of follow-up. Associations of cholesterol changes with disease activity and drug treatment were evaluated using repeated measures analysis with mixed effect linear models to model the within-subject covariance over time. Results: Mixed effect models controlling for traditional CV risk factors, TEAR treatment, and baseline prednisone and statin use demonstrated significant inverse associations of RA disease activity with changes in cholesterol over time. Decreases in DAS28, CRP, or ESR were associated with increases in HDL-C, LDL-C, and TC in all treatment groups (p values <0.001-0.035). TT was strongly associated with higher HDL-C and lower LDL-C and TC/HDL-C ratios (p values <0.001) compared to MTX monotherapy and MTX + ETA over two year follow-up. Conclusion: Decreases in RA disease activity over long term follow-up was associated with increases in cholesterol in early RA patients treated with either biologic or non-biologic therapies. The use of TT over two year follow-up was associated with higher HDL-C and lower LDL-C and TC/HDL-C ratios compared to MTX monotherapy or MTX + ETA combination therapy. This article is protected by copyright. All rights reserved.
    Article · Nov 2015 · Arthritis and Rheumatology
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    [Show abstract] [Hide abstract] ABSTRACT: Objective: To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). Methods: We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. Results: The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. Conclusion: This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.
    Full-text available · Article · Nov 2015
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement. Methods: We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry. The test set included those with good response or no response to tumour necrosis factor (TNF) inhibitors at 14 weeks by European League Against Rheumatism criteria. The validation set included subjects with good, moderate or no response at 12 weeks. Total serum type I IFN activity, IFN-α and IFN-β activity were measured using a functional reporter cell assay. Results: In the test set, an increased ratio of IFN-β to IFN-α (IFN-β/α activity ratio) in pretreatment serum associated with lack of response to TNF inhibition (p=0.013). Anti-cyclic citrullinated peptide antibody titre and class of TNF inhibitor did not influence this relationship. A receiver-operator curve supported a ratio of 1.3 as the optimal cut-off. In the validation set, subjects with an IFN-β/α activity ratio >1.3 were significantly more likely to have non-response than good response (OR=6.67, p=0.018). The test had 77% specificity and 45% sensitivity for prediction of non-response compared with moderate or good response. Meta-analysis of test and validation sets confirmed strong predictive capacity of IFN-β/α activity ratio (p=0.005). Conclusions: Increased pretreatment serum IFN-β/α ratio strongly associated with non-response to TNF inhibition. This study supports further investigation of serum type I IFN in predicting outcome of TNF inhibition in RA.
    Article · Nov 2015 · Annals of the rheumatic diseases
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: Anti-citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA). However, the molecular basis for ACPA production is still unclear. The purpose of this study was to determine if circulating plasmablasts from RA patients produce ACPAs and if Porphyromonas gingivalis (P. gingivalis) facilitates the generation of ACPAs. Methods: Using a single cell antibody cloning approach, we generated 217 and 110 monoclonal recombinant antibodies from circulating plasmablasts of 7 RA patients and 4 healthy controls, respectively. Antibody reactivity to citrullinated antigens was tested by the 2(nd) generation of anti-cyclic citrullinated peptide (CCP) kit and ELISAs against citrullinated human antigens. Antibody reactivity to P. gingivalis was tested by ELISAs against outer membrane antigens (OMAs) and citrullinated enolase from P. gingivalis. Results: 19.5% of plasmablast-derived antibodies from CCP-positive RA patients, but none from the CCP-negative RA patient or healthy controls, specifically recognized citrullinated antigens. The immunoglobulin genes encoding these ACPAs were highly mutated with increased replacement/silent mutation ratios, suggesting the involvement of active antigen selection in ACPA generation. Interestingly, 63% of the ACPAs cross-reacted with OMAs and/or citrullinated enolase from P. gingivalis. The reactivity of ACPAs against citrullinated proteins from P. gingivalis was confirmed by immuno blot and mass spectrometry. Furthermore, germ-line reversions of some ACPAs completely eliminated their reactivity to citrullinated human antigens but retained their reactivity to P. gingivalis. Conclusion: These results suggest that circulating plasmablasts in RA patients produce ACPAs and this process may be facilitated by the anti-P. gingivalis immune responses. This article is protected by copyright. All rights reserved.
    Article · Oct 2015 · Arthritis and Rheumatology
  • Abhijeet Danve · James O'Dell
    [Show abstract] [Hide abstract] ABSTRACT: Ankylosing Spondylitis poses significant challenges in terms of early diagnosis, assessment of disease activity, predicting response to the treatment and monitoring radiographic progression. With better understanding of underlying immunopathogenesis, effective targeted therapies are available which improve symptoms, quality of life and possibly slow the radiographic progression. There has been a growing interest in the discovery of biomarkers for defining various aspects of disease assessment and management in Ankylosing Spondylitis. The C-reactive protein and HLA-B27 are most commonly used biomarkers. This review describes many other newer biomarkers which have potential clinical applications in this chronic inflammatory disease.
    Article · Oct 2015 · International Journal of Rheumatic Diseases
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: The aim of this study was to investigate omega-3 fatty acid (FA) supplement use and omega-3 FAs in erythrocyte membranes [omega-3 FA % in erythrocyte membranes (RBC)] and their association with anti-CCP autoantibodies in a population without RA, but who are at genetic risk for RA. Methods: The multicentre Studies of the Etiology of RA (SERA) cohort includes RA-free subjects who are first-degree relatives of RA probands or are enriched with the HLA-DR4 allele. In a nested case-control study, 30 SERA cases were identified who were anti-CCP2 antibody positive. We further identified 47 autoantibody negative controls, frequency matched to cases on age at study visit, sex, race and study site. Anti-CCP2 status, self-reported omega-3 FA supplement use and omega-3 FA % in RBCs were obtained from a single visit. Results: Anti-CCP2 positive cases were less likely than controls to report omega-3 FA supplement use (odds ratio: 0.14; 95% CI 0.03, 0.68). In addition, the likelihood of anti-CCP2 positivity was inversely associated with total omega-3 FA % in RBCs (odds ratio: 0.47; 95% CI 0.24, 0.92, for a s.d. increase). Conclusion: The inverse association between anti-CCP2 positivity and self-reported omega-3 FA supplement use and omega-3 FA % in RBCs suggests that omega-3 FAs may protect against the development of RA-related autoimmunity in pre-clinical RA.
    Article · Sep 2015 · Rheumatology (Oxford, England)
  • [Show abstract] [Hide abstract] ABSTRACT: To assess and compare the impact of total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Rheumatologist-diagnosed arthritis patients undergoing primary TKA during 1999-2012 were identified. Indices of pain (overall, index and contralateral knee) and HRQoL were obtained in three consecutive 6-month intervals: pre-operative (baseline), peri-operative and post-operative (recovery). Descriptive statistics and one-way ANOVA were used to compare TKA outcomes by diagnosis, whereas effect sizes and standardized response means (SRM) were calculated between baseline and recovery. Of the participating 18,897 patients, 834 RA (5.3%) and 315 OA (10.2%) patients had undergone index TKA at similar mean ages (65 and 68 years). Post TKA, significant improvements were observed for most domains of pain, function and HRQoL within both disease groups, with greater impact in OA. By SRM, maximum improvement was shown in index knee pain (SRM: RA -1.33 OA -1.34; Effect sizes: RA -1.75 vs. OA -1.94). HAQ II and SF-36 PCS were the most responsive HRQoL indices in detecting post-TKA improvement in RA. A diagnosis of RA, lower income, and pre-operative anxiety were independently associated with lower improvements in index knee pain following TKA. TKA is highly effective in reducing clinically relevant knee pain to a greater extent than other subjective HRQoL indices in patients with RA, although this improvement is less marked as compared to OA patients. TKA serves as a "time machine" via which patients can return to a less disabled lifestyle, before the arthritic process catches up. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    Article · Jul 2015 · Arthritis and Rheumatology
  • Abhijeet Danve · James O'Dell
    [Show abstract] [Hide abstract] ABSTRACT: Primary systemic vasculitis is a group of heterogeneous disorders, characterized by inflammation of blood vessels causing end organ damage from ischemia, aneurysm formation or dissection. Delay in the early diagnosis owing to non-specific symptoms, lack of definitive serological tests, limited availability of biopsy and standard imaging tests pose significant challenge in the management of these diseases. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning is being increasingly used in the management of systemic vasculitis, especially the large vessel vasculitides: giant cell arteritis (GCA) and Takayasu arteritis (TAK). FDG-PET involves detection of positron rays emitted by FDG, a fluorinated glucose analogue which is avidly taken up by metabolically active inflammatory cells in the walls of involved blood vessels. 18F-FDG-PET scan, especially when combined with computed tomography or magnetic resonance imaging (MRI) can give information about active inflammation as well as structural damage associated with vasculitis. In patients with GCA, FDG-PET has acceptable sensitivity and specificity for the early diagnosis in non-cranial GCA, cranial GCA with negative biopsy, assessment of immediate response to treatment, predicting prognosis, but has limited value in serial follow-up and prediction of relapses. In TAK, FDG-PET can be useful for early diagnosis and probably for serial assessment of disease activity. FDG-PET has a limited role in medium and small vessel vasculitis. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.
    Article · Jul 2015 · International Journal of Rheumatic Diseases
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    [Show abstract] [Hide abstract] ABSTRACT: Objective: Malondialdehyde-acetaldehyde (MAA) adducts are a product of oxidative stress associated with tolerance loss in several disease states. This study was undertaken to investigate the presence of MAA adducts and circulating anti-MAA antibodies in patients with rheumatoid arthritis (RA). Methods: Synovial tissue from patients with RA and patients with osteoarthritis (OA) were examined for the presence of MAA-modified and citrullinated proteins. Anti-MAA antibody isotypes were measured in RA patients (n = 1,720) and healthy controls (n = 80) by enzyme-linked immunosorbent assay. Antigen-specific anti-citrullinated protein antibodies (ACPAs) were measured in RA patients using a multiplex antigen array. Anti-MAA isotype concentrations were compared in a subset of RA patients (n = 80) and matched healthy controls (n = 80). Associations of anti-MAA antibody isotypes with disease characteristics, including ACPA positivity, were examined in all RA patients. Results: Expression of MAA adducts was increased in RA synovial tissue compared to OA synovial tissue, and colocalization with citrullinated proteins was found. Increased levels of anti-MAA antibody isotypes were observed in RA patients compared to controls (P < 0.001). Among RA patients, anti-MAA antibody isotypes were associated with seropositivity for ACPAs and rheumatoid factor (P < 0.001) in addition to select measures of disease activity. Higher anti-MAA antibody concentrations were associated with a greater number of positive antigen-specific ACPA analytes (expressed at 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 ACPAs. These results support speculation that MAA formation may be a cofactor that drives tolerance loss, resulting in the autoimmune responses characteristic of RA.
    Full-text available · Article · Mar 2015 · Arthritis and Rheumatology
  • Manpreet K Sethi · James R O'Dell
    [Show abstract] [Hide abstract] 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.
    Article · Jan 2015 · Current Opinion in Rheumatology