Whitney Palmer

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Methotrexate Associated with “Profound” Improvements in RA

Published on the June 27, 2016, Rheumatology Network website

By Whitney L.J. Howell

Methotrexate therapy in patients with rheumatoid arthritis can cause significant changes in clinical disease activity, researchers say.

The study appears in the June 16 issue of RMD Open.

To date, researchers said, there have been no studies into the mechanism of action of methotrexate which look at serial prospective measures of serum cytokines and simultaneous measures of pharmacokinetics and clinical variables.

In this prospective, open-label, long-term mechanism of action study, investigators looked to describe changes in immune parameters that are observed during long-term methotrexate therapy in patients with active rheumatoid arthritis. They also wanted to explore correlations with simultaneously measured methotrexate pharmacokinetic parameters.

Led by Joel M. Kremer, M.D., from the Division of Rheumatology at Albany Medical College, researchers demonstrated that methotrexate treatment is associated with serum interleukin-6 (IL-6) and interleukin-8 (IL-8) decreases. This three-year study, conducted in the 1990s, also shows these drops correlate well with long-term, sequential measures of methotrexate pharmacokinetics and with clinical outcomes.

Throughout the study, 17 patients received single, weekly 7.5 mg doses of methotrexate. The doses were adjusted for efficacy and toxicity throughout the study, and researchers gathered baseline measures for disease activity and took follow-up measurements every six months for three years. Each clinical evaluation assessed serum cytokine measurements in blood together with lymphocyte surface immunophenotypes and stimulated peripheral blood mononuclear cell cytokine production.

According to study results, cytokine concentrations revealed several significant correlations over time with disease activity measures. The two strongest were: interleukin-6 (r=0.45, p<0.0001 for swollen joints and r=0.32, p=0.002 for tender joints) and interleukin-8 (r=0.25, p=0.01 for swollen joints).

Results also found significant decreases for serum interleukin-1B, interleukin-6, and interleukin-8 from baseline measurements with interleukin-6 being the most substantial change (p<0.001). Data also revealed noteworthy increases from baseline for interleukin-2 release from peripheral blood mononuclear cells ex vivo (p<0.01). However, the change in swollen joint count correlated inversely with the changes for methotrexate (r=-0.63, p=0.007).

“These data strongly support the notion that MTX (methotrexate) mediates profound and functionally relevant effects on the immunological hierarchy in the RA lesion,” the researchers wrote.

Ultimately, investigators said, knowing methotrexate can significantly affect serum interleukin-6 will increase understanding around methotrexate’s mechanism of action. It also offers insight into further changes in transaminase levels and possible additive effects on interleukin-6 when used with biological response modifiers and Janus kinase inhibitors.

“The compelling relationship between the immune changes reported and simultaneous pharmacokinetic measures strongly suggest that the findings are related to methotrexate intervention and are not simply a surrogate for general disease improvement,” investigators said.

In addition, they said, the significant decrease in serum interleukin-6 observed with methotrexate may further explain increases in transaminase enzymes when the drug is combined with either interleukin-6 or Janus kinase inhibitors.

To read the article at its original location: http://www.rheumatologynetwork.com/rheumatoid-arthritis/methotrexate-associated-%E2%80%9Cprofound%E2%80%9D-improvements-ra?GUID=EF943FEE-BD0C-44C7-A1BC-C82F32210979&XGUID=&rememberme=1&ts=28062016


June 28, 2016 Posted by | Healthcare | , , , , , , | Leave a comment

High BMI Not a Factor in Axial Spondyloarthritis

Published on the June 22, 2016, Rheumatology Network website

By Whitney L.J. Howell

Researchers say it is not necessary to take body mass index into account when assessing disease activity in axial spondyloarthritis patients.

The study appears in the June 16 issue of RMD Open.

Physicians primarily rely on two measures to assess axial spondyloarthritis (axSpA) and ankylosing spondylitis disease status:  the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). While BASDAI relies on patient-reported outcomes to measure ankylosing spondylitis in patients, ASDAS combines patient-reported outcomes with C reactive protein (CRP) to assess axial spondyloarthritis status.

Because adipose tissue is frequently associated with increased production of pro-inflammatory cytokines, such as C reactive protein, investigators hypothesized whether an elevated body mass index could be an accurate disease-activity indicator. Obesity, measured by body mass index (BMI), is associated with increased levels of C reactive protein (CRP). High levels occur in response to inflammation, including that associated with ankylosing spondylitis.

Led by Roxana Rubio Vargas of the Leiden University Medical Center in The Netherlands, researchers found body mass index only influences CRP blood serum levels in women. But, the impact is not clinically relevant.

Knowing whether body mass index and excess adipose tissue contributed to CRP levels and self-reported outcomes could influence how providers guide patients on how best to control their axial spondyloarthritis.

Using patients and data from the existing SPondyloArthritis Caught Early (SPACE) cohort, launched in January 2009, researchers evaluated 428 patients over age 16 who had chronic back pain for more than three months, but less than two years. Investigators divided patients into normal weight (body mass index ≤24.9) and overweight (≥25). Collected C reactive protein levels of ≥5 mg/L were considered elevated.

Of the 428 patients, 168 (39.3%) fulfilled the Assessment in SpondyloArthritis International Society axial spondyloarthritis classification. This group had statistically lower rates of overweight and obesity— 18.4% and 11.9%, respectively — than those without the condition — 31.5% and 14.2%, respectively. Among patients with axial spondyloarthritis and those without, overweight patients had statistically significant higher C reactive protein rates (p=0.02 and 0.01, respectively). Researchers also discovered body mass index increases C reactive protein blood serum levels by 0.35 mg/L for each body mass index point – but only for women.

Overall, the researchers found, the impact of body mass index on C reactive protein in women isn’t enough to warrant using it as a measure of disease activity. It also doesn’t significantly impact any patient-reported outcomes.

“In general, it is not necessary to take BMI into account when assessing disease activity by ASDAS in axSpA patients with high BMI, but there may be a slight increase in ASDAS in female patients with very high BMI,” researchers wrote.

Further research into the influence of body mass index on CRP is needed, though. Researchers recommend conducting MRI and spectroscopy studies on a larger sample size of overweight women with axial spondyloarthritis to achieve more accurate results.

To read the story at its original location: http://www.rheumatologynetwork.com/spondyloarthritis/high-bmi-not-factor-axial-spondyloarthritis

June 23, 2016 Posted by | Healthcare | , , , | Leave a comment

Challenges in the Radiologist-Technologist Relationship

Published on the June 9, 2016, DiagnosticImaging.com website

By Whitney L.J. Howell

In radiology, there’s no more important – no closer relationship – than the one between the radiologist and the radiologic technologist (RT). You work together day-in and day-out, but there’s no guarantee that your partnership is as healthy as it should be.

According to industry experts, effective radiologist-RT work habits should share some of the same characteristics, enabling those pairs to provide quality patient care. But, radiology has changed drastically over the past 25 years, and stumbling blocks challenge how smoothly your daily interactions will be in today’s environment.

“I remember the days of film in the 1990s when technologists would come into the reading room and hang the film,” said Paul Nagy, PhD, associate professor of radiology and radiological sciences at Johns Hopkins School of Medicine. “It was great because of the cross-section of interaction that happened when the radiologists looked at the film and gathered information from the tech for diagnostic purposes. But, there are several strains on the relationship today.”

There are strategies in place that are working to fortify the partnership, though, because this interaction is necessary to produce an actionable radiology report.

“The radiologist is very dependent upon the technologist to get the most information from patients,” said Michael Delvecchio, technical director of radiology at Brigham and Women’s Hospital. “It helps them get better reads and provide a better diagnosis.”

To read the remainder of the article at its original location: http://www.diagnosticimaging.com/practice-management/challenges-radiologist-technologist-relationship

June 9, 2016 Posted by | Healthcare | , , , , , | Leave a comment

Omega-3 Fatty Acids May Have a Protective Effect in RA

Published on the June 6, 2016, Rheumatology Network website

By Whitney L.J. Howell

The Omega-3 fatty acids found in certain fish can provide a possible protective benefit to individuals with rheumatoid arthritis and other related autoimmunity conditions. In fact, the benefit is strongest among those who have a genetic susceptibility to rheumatoid arthritis.

An Annals of Rheumatic Diseases studypublished in May, “Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects are at risk for rheumatoid arthritis,” found that people with the human leucocyte antigen class II genetic susceptibility are most likely to experience the positive result.

It’s the association between the n-3 fatty acids and anti-CCP2, the antibody that can pinpoint early rheumatoid arthritis development, as well as rheumatoid factor positivity, that supports the fatty acid’s ability to be protective, the study revealed. And, this work supports and furthers existing research, investigators said.

“Previous studies suggest n-3 [fatty acids] could possibly protect against the development of rheumatoid arthritis where our results suggest that the mechanism behind this might be through the prevention of autoantibody development,” they wrote. “More importantly, our results suggest the effect of longer-chain n-3 [fatty acids] on rheumatoid arthritis-related autoimmunity could depend on shared epitope status.”

Researchers recruited 2,166 participants from the Studies of the Etiology of Rheumatoid Arthritis (SERA) multi-center study, including those who didn’t have rheumatoid arthritis but were at-risk. They included two groups: first-degree relatives of persons with rheumatoid arthritis and parents of children with the allele for type 1 diabetes.

Each participant completed a 68-count joint exam and a questionnaire about environmental risk factors to evaluate the association between n-3 fatty acid supplement use and the prevalence of rheumatoid factor and anti-CCP2, the antibody that can pinpoint early rheumatoid arthritis development.

SERA participants were screened for shared epitope, the strongest predictor of seropositive rheumatoid arthritis. They were considered shared epitope positive if they a subtype of human leucocyte antigen-antigen D related 4 or –antigen D related 1 was present in their blood.

Investigators also conducted a 136-participant nested case-control study to understand the association between rheumatoid factor and anti-CCP2 positivity and n-3 fatty acid percentage in red blood cells.

According to results, in the shared epitope-positive group, rheumatoid factor cases are more likely to have lower levels of total red blood cell n-3 fatty acid percentage compared to the control group (OR 0.26, 95% CI 0.09 to 0.77, p=0.02). There was no association observed among the shared epitope-negative group.

In addition, data revealed an inverse association between anti-CCP2 positivity and the increasing total of red blood cell n-3 fatty acid percentage. (0.59, 95% CI 0.36 to 0.96) and the longer-chain n-3 fatty acids, eicosapentaenoic and docosahexaenoic acid (OR 0.56, 95% CI 0.34 to 0.92). The increasing total red blood cell n-3 fatty acid percentage was also inversely associated with anti-CCP2 positivity in shared epitope-positive participants (OR 0.44, 95% CI 0.21 to 0.93, p=0.03).

Based on questionnaire data, n-3 fatty acid supplement use was connected to a lower prevalence of anti-CCP2 in the shared epitope-positive group.

However, additional research is needed to study the interaction between n-3 fatty acids and shared epitope, as well as the progression of clinically-apparent rheumatoid arthritis. Doing so, investigators said, could offer insight into the group most likely to benefit from prevention strategies and how they are timed.

To read the article at its original location: http://www.rheumatologynetwork.com/rheumatoid-arthritis/omega-3-fatty-acids-may-have-protective-effect-ra

June 7, 2016 Posted by | Healthcare | , , , , | Leave a comment

Common Genetic Pathways Implicated RA and SLE

Published on the May 31, 2016, Rheumatology Network website

By Whitney L.J. Howell

Rheumatoid arthritis and lupus are distinct conditions that present in unique ways, but they do share various genetic risk factors. A recent study revealed a new risk locus for both diseases.

Previously, the genetic overlap between the two hadn’t been thoroughly examined. But, a study published in the May Annals of Rheumatic Diseases identified additional risk loci that are shared between rheumatoid arthritis and lupus.

Using genome-wide association studies, the study, “A combined large-scaled meta-analysis identifies COG6 as a novel shared risk locus for rheumatoid arthritis and systemic lupus erythematosus,” revealed the genetic variant rs9603612 is located near the COG6 (component of oligomeric Golgi complex 6) gene.

COG6 is located on chromosome 13q14.11, and it’s crucial to proper protein sorting and glycosylation. However, its role in immune-mediated disorders remains unknown.

This study is the first comprehensive, large-scale analysis that looks into the genetic overlap between both disorders. Small sample sizes has been a limiting factor to-date.

“Our results highlight the existence of a relevant genetic correlation between both diseases, as well as the influence of common molecular mechanisms in their pathophysiology,” the authors wrote. “Since common genetic pathways are implicated in rheumatoid arthritis and lupus, a reclassification of patients from a genetic point of view will lead to more specific and effective therapeutic procedures.”

Overall, researchers included 17,552 patients with rheumatoid arthritis, 4,194 patients with lupus, and 46,907 control patients. Data came from Sweden, the United Kingdom, Germany, Italy, Spain, The Netherlands, and the United States.

Through silico expression quantitative trait locus analysis, researchers learned the associated polymorphism acts like a regulator variant that influences COG6 expression. In particular, rs9603612 impacts the transcription factor binding and is linked to gene target expression, most likely regulating COG6 expression in monocytes.

According to investigators, the protein-protein interaction and gene ontology enrichment analyses pointed to an overlap with specific biological processes. Results pointed specifically to the type I interferon signaling pathway. Additionally, the genetic correlation and polygenic risk score analyses showed cross-phenotype associations between rheumatoid arthritis and lupus.

Bivariate analysis revealed a significant genetic correlation between rheumatoid arthritis and lupus. Polygenic risk score analysis showed significant differences between the case groups and controls and that lupus cases had a significant enrichment of rheumatoid arthritis-risk alleles.

The findings, they said, point to rs9603612 being a good candidate for being the casual variant involved in the genetic predisposition of autoimmune disorders.

To read the story at its original location: http://www.rheumatologynetwork.com/lupus/common-genetic-pathways-implicated-ra-and-sle

June 2, 2016 Posted by | Healthcare, Science | , , , , | Leave a comment


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