Ted R. Mikuls

American College of Rheumatology 2008 Recommendations for the Use of Nonbiologic and Biologic Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis

Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.

Remission of rheumatoid arthritis in clinical practice: Application of the American College of Rheumatology/European League Against Rheumatism 2011 remission criteria

OBJECTIVEnTo describe use of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) remission criteria in clinical practice.nnnMETHODSnRemission was examined using data on 1,341 patients with RA (91% men) from the US Department of Veterans Affairs RA (VARA) registry (total of 9,700 visits) and 1,153 patients with RA (25.8% men) in a community rheumatology practice (Arthritis and Rheumatology Clinics of Kansas [ARCK]) (total of 6,362 visits). Cross-sectional and cumulative probabilities were studied, and agreement between the various remission criteria was assessed. Aspects of reliability of the criteria were determined using Boolean-based definitions, as well as the Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) scoring methods proposed by the ACR/EULAR joint committee.nnnRESULTSnWhen the 3-variable ACR/EULAR definition of remission recommended for use in community practice (swollen and tender joint counts ≤1, and visual analog scale score for patients global assessment of disease activity ≤1) was applied, cross-sectional remission was 7.5% (95% confidence interval [95% CI] 6.4, 8.7%) for ARCK and 8.9% (95% CI 7.9, 9.9%) for VARA, and cumulative remission (remission at any observation) was 18.0% (for ARCK) and 24.4% (for VARA), over a mean followup of ∼2.2 years. Addition of the erythrocyte sedimentation rate or C-reactive protein level to the criteria set reduced remission to 5.0-6.2%, and use of the CDAI/SDAI increased the proportions to 6.9-10.1%. Moreover, 1.8-4.6% of the patients met remission criteria at ≥2 visits. Agreement between criteria definitions was good, as assessed by kappa statistics and Jaccard coefficients. Among patients in remission, the probability of a remission lasting 2 years was 6.0-14.1%. Among all patients, the probability of a remission lasting 2 years was <3%. Remission status and examination results for each patient varied substantially among physicians, as determined by multilevel analyses.nnnCONCLUSIONnCross-sectional remission occurred in 5.0-10.1% of the patients in these cohorts, with cumulative remission being 2-3 times greater; however, long-term remission was rare. Problems with reliability and agreement limit the usefulness of these criteria in the individual patient. However, the criteria can be an effective method for measuring clinical status and treatment effect in groups of patients in the community.

Persistence and Dose Escalation of Tumor Necrosis Factor Inhibitors in US Veterans with Rheumatoid Arthritis

Objective. Limited evidence exists comparing the persistence, effectiveness, and costs of biologic therapies for rheumatoid arthritis in clinical practice. Comparative effectiveness studies are needed to understand real-world experience with these agents. We evaluated treatment patterns, costs, and effectiveness of tumor necrosis factor inhibitor (TNFi) agents in patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry. Methods. Observational data from the VARA registry and linked administrative databases were analyzed. Longitudinal data from VARA patients initiating adalimumab (ADA), etanercept (ETN), or infliximab (IFX) from 2003 (the date all agents were available within the Veteran Affairs) to 2010 were analyzed. Outcomes included Disease Activity Score using 28 joints (DAS28), treatment persistence, dose escalation, and direct costs of drugs and drug administration. Results. For 563 eligible patients, baseline DAS28, DAS28 improvements, and persistence on initial treatment were similar across agents. Fewer patients receiving ETN (n = 5/290; 2%) underwent dose escalation than did patients taking ADA (n = 32/204; 16%) or IFX (n = 44/69; 64%). Annual costs for first course of TNFi therapy were lower for injectable ADA (

Cardiovascular Events Are Not Associated with MTHFR Polymorphisms, But Are Associated with Methotrexate Use and Traditional Risk Factors in US Veterans with Rheumatoid Arthritis

13,100 US) and ETN (

Dual-Energy X-Ray Absorptiometry and Evaluation of the Osteoporosis Self-Assessment Tool in Men With Rheumatoid Arthritis

13,500 US) than for intravenously administered IFX (

Impact of Obesity and Adiposity on Inflammatory Markers in Patients With Rheumatoid Arthritis

16,900 US). Conclusion. Despite similar persistence and clinical disease activity for these TNFi agents, rates of dose escalation were highest with ADA and IFX. Higher overall costs were noted for IFX without increases in effectiveness.

Quality of care in gout: from measurement to improvement

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 effects of physician specialty and patient comorbidities on the use and discontinuation of coxibs

Males with rheumatoid arthritis (RA) are at risk for osteoporosis but infrequently undergo dual-energy X-ray absorptiometry (DXA). We examined the frequency of DXA in males enrolled in the Veterans Affairs Rheumatoid Arthritis Registry. The Osteoporosis Self-Assessment Tool (OST) index, a formula using age and weight, was calculated for all subjects. DXA was performed on 282 (35.5%) of the males who were younger (p < 0.01), had lower mean OST index score (p < 0.05), and were more likely to have been prescribed prednisone (p < 0.01) than subjects without DXA. Low bone mass (T-score < -1) was present in 73% of subjects with DXA; 37% of subjects with low-risk OST index scores had normal bone mineral density (BMD) compared with 5.6% of those with high-risk OST index scores (p < 0.01). There was a significant but modest correlation between BMD and the OST index (r = 0.17, p < 0.01). No OST score had a sensitivity and specificity of more than 80%. Association between OST index and BMD was strongest in non-Hispanic whites, subjects older than 60 yr, and smokers. DXA was underutilized in males with RA. The OST index correlated with low bone mass but could not reliably predict osteoporosis in this population.

Folic acid pathway single nucleotide polymorphisms associated with methotrexate significant adverse events in United States veterans with rheumatoid arthritis.

The C‐reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) are important disease activity biomarkers in rheumatoid arthritis (RA). This study aimed to determine to what extent obesity biases these biomarkers.