Amy C. Cannella

Therapies for Active Rheumatoid Arthritis after Methotrexate Failure

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.)

Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitis

UNLABELLED Antibody titers to P. gingivalis are increased in patients with rheumatoid arthritis and are associated with disease-specific autoimmunity. BACKGROUND Periodontitis (PD) has been implicated as a risk factor for rheumatoid arthritis (RA). We sought to characterize antibody titers to P. gingivalis (a pathogen in PD) in subjects with RA, PD, and in healthy controls and to examine their relationship with disease autoantibodies. METHODS P. gingivalis antibody was measured in subjects with RA (n=78), PD (n=39), and in controls (n=40). Group frequencies of bacterial titer elevations were compared using the Chi-square test and antibody titers were compared using non-parametric tests. Correlations of P. gingivalis titer with C-reactive protein (CRP), antibody to cyclic citrullinated peptide (anti-CCP), and rheumatoid factor (RF) were examined in those with RA while CRP and autoantibody concentrations were compared based on seropositivity to P. gingivalis. RESULTS Antibody titers to P. gingivalis were highest in PD, lowest in controls, and intermediate in RA (p=0.0003). Elevations in P. gingivalis (titer> or =800) were more common in RA and PD (67% and 77%, respectively) than in controls (40%) (p=0.002). In RA, there were significant correlations with P. gingivalis titer with CRP, anti-CCP-IgM, and -IgG-2. CRP (p=0.006), anti-CCP-IgM (p=0.01) and -IgG2 (p=0.04) concentrations were higher in RA cases with P. gingivalis titers > or =800 compared to cases with titers <800. CONCLUSION Antibodies to P. gingivalis are more common in RA subjects than controls, although lower than that in PD. Associations of P. gingivalis titers with RA-related autoantibody and CRP concentrations suggests that infection with this organism plays a role in disease risk and progression in RA.

Regional distribution of adult rheumatologists

OBJECTIVE To analyze the distribution of rheumatology practices in the US and factors associated with that distribution, in order to better understand the supply of the rheumatology workforce. METHODS Using the American College of Rheumatology membership database, all practicing adult rheumatologist office addresses were mapped with ArcView software. The number of rheumatologists per Core Based Statistical Area (CBSA) was calculated. To investigate whether sociodemographic factors correlated with clustering of rheumatologists, covariates from the 2010 US Census for each CBSA, including age, sex, race/ethnicity, and median household income, were modeled. RESULTS Many CBSAs, predominantly smaller micropolitan areas, did not have a practicing rheumatologist. For some of these smaller micropolitan areas (with populations of at least 40,000), the closest practicing rheumatologist was more than 200 miles away. However, we also identified several more-populous areas (populations of 200,000 or more) without a practicing rheumatologist. Greater numbers of rheumatologists were more likely to practice in areas with higher population densities and higher median incomes. More rheumatologists were also found in CBSAs in which there were rheumatology training programs. CONCLUSION These findings demonstrate that many smaller regions of the country have no or few practicing adult rheumatologists. Patients with chronic rheumatic conditions in these areas likely have limited access to rheumatology care. Policy changes could address potential regional rheumatology workforce shortages, but limitations of the current data would need to be addressed prior to implementation of such changes.

Evolution of Musculoskeletal Ultrasound in the United States: Implementation and Practice in Rheumatology

Introduction Ultrasonography (US) uses nonionizing sound waves to produce 2or 3-dimensional gray-scale images. Although adopted earlier in other fields of medicine, the first US descriptions of normal and abnormal musculoskeletal (MS) tissues were published in 1958 and 1972, respectively (1,2). The use of color/power Doppler for synovitis was first described in 1994 (3). Annual publications on MSUS have increased exponentially from 7 in 1991 to 175 in 2011 (4). In addition to orthopedic surgery, physiatry, and podiatry, the use of MSUS has gained increasing acceptance in the field of rheumatology (5,6). Combining clinical findings, a strong understanding of the immunobiology of rheumatic diseases, and the potential for realtime dynamic imaging makes the use of MSUS a powerful addition to the diagnostic skills of the rheumatology provider. Applications of MSUS include the diagnosis of inflammatory and noninflammatory rheumatic disease, the assessment of an individual’s response to treatment, and guidance for procedures (7–9) (Table 1). MSUS is gaining acceptance as an imaging modality among rheumatologists, but little has been published regarding the experience in the United States. Many entities, including the Ultrasound School of North American Rheumatologists (USSONAR) and the American College of Rheumatology (ACR), have taken a proactive role in the use of MSUS by offering educational courses, training educators, and developing a set of reasonable use criteria and certification. Despite many challenges in academic settings, inroads have been made at the fellowship training level by clinician educators to incorporate MSUS into individual program curricula. This review describes the evolution of this modality with its beginnings in Europe and its further adoption in the United States, reviews the necessary components for its practice, examines the economic and education-related challenges to its implementation, and offers solutions and resources to overcome these barriers.

Musculoskeletal Ultrasound Objective Structured Clinical Examination: An Assessment of the Test

To determine the reliability and validity of an objective structured clinical examination (OSCE) for musculoskeletal ultrasound (MSUS).

Early rheumatoid arthritis : Pitfalls in diagnosis and review of recent clinical trials

The treatment of rheumatoid arthritis (RA) has changed dramatically in the past decade as advancements in the understanding of the pathobiology of the disease have led to novel therapeutic agents. The recognition that early diagnosis and treatment leads to improvements in morbidity and mortality has altered the therapeutic strategy such that early therapy is now considered the standard of care.This review focuses on the challenges in making the diagnosis of early RA, including a broad differential diagnosis for inflammatory polyarthritis, poor performance of the standard classification criteria, difficulty in clinical assessment of synovitis, absence of absolute laboratory tests, inability of conventional radiography to detect bony changes early, and barriers to rheumatology care. Additionally, the pathogenesis of RA is highlighted, with particular emphasis on cytokine biology as it relates to therapeutic regimens. Relevant clinical trials in early RA are reviewed and discussed, including trials of combination disease-modifying antirheumatic drugs and biological therapy. The role of induction therapy as a novel therapeutic approach is highlighted. The search for predictors of response is reviewed and the external validity of the trials is analysed. Finally, the trials in early RA therapy suggest that swift intervention with combinations of medications is required for patients with severe RA. However, further research is needed to determine which regimen is appropriate for the individual patient with RA.

Generalizability of Patients With Rheumatoid Arthritis in Biologic Agent Clinical Trials.

Randomized controlled trials (RCTs) have consistently demonstrated the efficacy of biologic agents in treating patients with rheumatoid arthritis (RA) who satisfy strict eligibility criteria, yet studies report that a majority of RA patients in the US have had biologic treatment exposure. We identified the proportion of RA patients in clinical practice satisfying entry criteria for biologic agent RCTs.

Changes in Body Mass Related to the Initiation of Disease-Modifying Therapies in Rheumatoid Arthritis

Unintentional weight loss is important and can be predictive of long‐term outcomes in patients with rheumatoid arthritis (RA). This study was undertaken to assess how primary therapies for RA may influence changes in body mass index (BMI) in RA patients from a large administrative database.

Cardiovascular Risk and the Use of Biologic Agents in Rheumatoid Arthritis

Although patients with rheumatoid arthritis (RA) are recognized to be disproportionately impacted by cardiovascular disease (CVD), effective approaches of primary and secondary CVD prevention have not been well defined in this population. Given their robust disease-modifying potential and effects on both pro-inflammatory and pro-atherogenic pathways, there has been substantial speculation that biologic treatments may serve as a means of providing highly effective RA disease control while simultaneously reducing CVD risk in this high risk group. In this review, we examine available evidence relevant to the associations of approved biologic treatments with CVD outcomes in the context of RA.

Musculoskeletal Ultrasound Instruction in Adult Rheumatology Fellowship Programs

Musculoskeletal ultrasound (MSUS) in rheumatology in the US has advanced by way of promotion of certifications and standards of use and inclusion of core fellowship curriculum. In order to inform endeavors for curricular integration, the objectives of the present study were to assess current program needs for curricular incorporation and the teaching methods that are being employed.