Whitney Palmer

Healthcare. Politics. Family.

Study: This Corticosteroid Reduces OA Pain

Published on the April 4, 2016, Rheumatology Network website

By Whitney L.J. Howell

The extended-release corticosteroid FX006 (Zilretta) has been shown to have a maximal analgesic effect in patients with knee osteoarthritis (OA) over the standard TCA 40 mg suspension after an intra-articular injection.  However, the dose response rate for FX006 between 20mg and 40mg has, to-date, been unknown.

In an April 2 presentation entitled, “Sustained and Profound Analgesic Benefits in People With Osteoporosis of the Knee Using FX006, an Intra-Articular Extended-Release Formulation of Triamcinolone Acetonide: Results From a Double-Blind, Randomized, Parallel-Group, Dose-Ranging Study,” Philip Conaghan, from the University of Leeds in the United Kingdom discussed FX006 effectiveness over other options.

A total of 306 patients, with documented knee OA with Kellgren-Lawrence grade 2 or 3 and pain intensities from 5-to-9 on a scale of 1-to-10, were treated with either a single IA injection of 20mg or 40mg FX006 or a saline placebo. Baseline age, race, body mass index, and knee characteristics were similar across groups. Researchers monitored participants over 24 weeks for efficacy and safety. The primary endpoint was a change from baseline measures at week 12.

According to the results, Mixed Model Repeat Measures FX006 20mg demonstrated significant improvement in daily pain levels from weeks 1 through 9. FX006 also offered improvement from weeks 1 to 13. In the LOCF/BOCF analysis, FX006 20mg from weeks 1 through 8, and FX006 showed improvement from weeks 1 to 13. In a secondary analysis, FX006 performed better than the placebo for each week.

For all patients with OA, FX006 demonstrated higher efficacy than a placebo. FX006 20mg and 40mg reach maximum performance at week 5, and a phase 3 trial is underway to compare FX006 40mg with standard TCA suspension 40mg and placebo.

To read the article at its original location: http://www.rheumatologynetwork.com/osteoarthritis/study-corticosteroid-reduces-oa-pain

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April 13, 2016 Posted by | Healthcare | , , , | Leave a comment

OA Progression as Seen in a Biomarker Panel

Published on the Apr. 4, 2016, Rheumatology Network website

By Whitney L.J. Howell

There are better ways to predict knee osteoarthritis (OA) progression, according to a Duke University physician scientist reporting at OARSI 2016 World Congress.

Currently, most physicians rely on poor predictors, such as age, sex, body mass index, knee pain, general bone mineral content and joint space width, but osteoarthritis comes in phases, reported Virginia Kraus, M.D., Ph.D., of the Duke Molecular Physiology Institute.

Osteoarthritis is a disease associated with periods of inactivity with no more than 30 percent of individuals affected by the progression of knee OA at any one time. These periods of quiescence effect clinical trials — the majority of which in OA suffer from “low power” due to an inability to identify progressors, Dr. Kraus reported.

During an April 1 presentation at OARSI 2016 in Amsterdam earlier this month, Dr. Kraus reported that serum biomarkers may offer a more accurate measure of osteoarthritis progression.

“We developed a method of predicting OA progression based on a panel of mass spectrometry and ELISA based biomarkers. Markers predicting osteophyte progression were distinctly different from those predicting JSN progression. These results suggest that a select set of biomarkers identified from targeted and non-targeted analyses could significantly improve prediction of knee OA progression and could be useful for enriching knee OA clinical trials for progressors,” she reported.

The Kraus study pulled participant data from the Prediction of Osteoarthritis Progression cohort and Genetics of Generalized OA studies. Kraus’s team ran a mass spectrometry analysis to create a Multiple Reaction Monitoring (MRM) panel on 146 peptides (99 proteins) in serum that included synovial fluid (n=23), urine (n=45), and serum (n=40) from knee osteoarthritis radiographic progressors and non-progressors.

Dr. Kraus and colleagues found that MRM or ELISA-based biomarkers, in combination with clinical parameters, significantly improved the prediction of OA progression (all definitions) over clinical variables alone achieving AUCs ranging from 0.84-0.97.

Of the subject population, 82 percent were female with a mean age of 64 and mean BMI of 28. The percentage of each sample meeting the knee OA progress definition was:  75 percent ANY, 52 percent JSN, 66 percent osteophyte, and 29 percent KL progression. Age, gender, and BMI were only significant in predicting osteophyte progression.

Knee osteoarthritis progression was defined as any knee osteoarthritis  progression or osteophyte, joint space narrowing (JSN) or Kellgren Lawrence (KL) grade progression within four years. Any progression was predicted by 10 MRM markers; osteophyte progression by 7 MRM markers; JSN progression by 6 ELISA markers; and KL progression by 1 ELISA marker.

To read the article at its original location: http://www.rheumatologynetwork.com/osteoarthritis/oa-progression-seen-biomarker-panel

April 13, 2016 Posted by | Healthcare | , , | Leave a comment

Obesity as a Metabolic Pathway in Knee OA

Published on the April 4, 2016, Rheumatology Network website

By Whitney L.J. Howell

Obesity may have an independent effect on the risk of knee osteoarthritis through both metabolic pathways and mechanical loading, physicians report at the OARSI 2016 World Congress held in Amsterdam this month.

This was the conclusion of one of two OARSI studies that looked into whether it’s possible to discover how obesity leads to knee osteoarthritis and whether losing weight can relieve pressure on knee joints.

On April 1, Boston University School of Medicine’s Devyani Misra M.D., presented “Obesity, Sarcopenic Obesity or Sarcopenia: Which is a Greater Risk for Knee OA?,” and Wake Forest University’s Stephen Messier, Ph.D., delivered “Does Long-Term Intensive Diet and Exercise Reduce the Biomechanical Burden in Overweight and Obese Adults with Knee Osteoarthritis? The Intensive Diet and Exercise for Arthritis (IDEA) Trail.” The first discussed the association of body composition to knee osteoarthritis risk, and the second discussed how combining diet and exercise can alleviate pressure.

In Misra’s study, 2,787 patients were divided into four categories: 14 percent obese non-sarcopenic, 4 percent sarcopenic-obese, 17 percent sarcopenic non-obese, and 65 percent non-sarcopenic non-obese. Three hundred fifty five and 154 subjects developed incident ROA and incident SOA, respectively. Obesity and sarcopenic-obesity patients had a more than twofold increase in the risk of incident ROA. Sarcopenia had no increased risk.

Results indicate adipose tissue may have an independent effort on knee OA risk through metabolic pathways beyond solely mechanical effects.

“Even after accounting for mechanical loading (adjusting for body weight), adiposity defined by body composition was associated with increased risk of knee OA. No such association was noted for sarcopenia,” the researchers wrote.

In the second study, after 18 months, participants experienced weight loss — 2.0 percent (exercise), 9.5 percent (diet), and 11.4 percent (exercise and diet), respectively. Exercise included low-to-moderate intensity walking and resistance training three days a week.

Results from the first study indicate adipose tissue may have an independent effect on knee OA risk through metabolic pathways beyond solely mechanical effects. The second study showed a reduction in joint pressure could play a significant role in improving clinical outcomes and slowing disease.

To read the article at its original location: http://www.rheumatologynetwork.com/OARSI2016/obesity-metabolic-pathway-knee-oa

April 13, 2016 Posted by | Healthcare | , | Leave a comment

Study Reveals a Link between Heart Disease and Knee OA

Published on the April 5, 2016, Rheumatology Network website

By Whitney L.J. Howell

Severe knee osteoarthritis is modestly associated with an increased risk of all-cause and cardiovascular disease specific mortality, shows a study presented at the OARSI 2016 World Congress held in Amsterdam this month.

Individuals with cardiovascular disease (CVD) have increased odds of having knee osteoarthritis, as well as a higher likelihood of premature death. Study results suggested, however, other factors besides co-morbidities that could link osteoarthritis and mortality risk.

In an April 1 presentation titled, “Individuals with Severe Knee OA Are At Increased Risk of All-Cause and Cardiovascular Disease-Specific Mortality: The Johnston County Osteoarthritis Project,” Rebecca Cleveland, Ph.D., from the University of North Carolina at Chapel Hill, discussed how these associations were independent of comorbidities and socio-demographic measures linked to higher mortality.

Data on 4,403 participants, age 45 and older, in the Johnston County Osteoarthritis Project were analyzed to examine the association between baseline radiographic knee osteoarthritis measures and all-cause, cardiovascular disease-specific death. The original study enrollment included 3,185 individuals; an additional 1,218 joined as a cohort enrichment.

Researchers used the National Death Index date and cause-of-death records to assess vital status. They used the Kellgren-Lawrence (KL) grade of 2 in either knee to define knee ROA. Severe and symptomatic (sxOA) ROA received a KL grade 3. All models were adjusted for age, cohort (original or enrichment), gender, education, smoking, and self-reported high blood pressure, cancer, and diabetes, as well as heart disease and stroke.

Among participants, average age was 61, 63.5 percent were women, 35.2 percent were black, 36.1 percent didn’t complete high school, and 21.2 percent were smokers. Nearly 13.3 percent had diabetes, 10.1 percent had heart disease, slightly more than 1 percent had stroke and cancer each, and 39 percent had hypertension.

After follow-up at 14. 5 years, investigators determined that participants with knee radiographic osteoarthritis had significantly lower survival than those without it – 61.9 percent and 73.6 percent, respectively. After 24 years, severe, symptomatic knee osteoarthritis was modestly associated with an increased risk of all-cause and CVD-specific mortality.

“Our results suggest there may be mechanisms beyond comorbidities in the link between knee rOA and mortality risk that merit further investigation. Future studies should focus on potential interactions with comorbidities,” the authors wrote.

To read the article at its original location: http://www.rheumatologynetwork.com/OARSI2016/study-reveals-link-between-heart-disease-and-knee-oa

April 13, 2016 Posted by | Healthcare | , , | Leave a comment

Only Minimal Pain Relief from VitD for Knee Pain

Published on the April 5, 2016, Rheumatology Network website

By Whitney L.J. Howell

Current evidence about the benefits of Vitamin D supplementation in knee osteoarthritis (OA) is contradictory. This finding disagrees with observational evidence that points to a positive impact, shows a study presented at the OARSI 2016 World Congress held in Amsterdam this month.

Comparing the effects of Vitamin D supplementation to a placebo on knee pain, knee cartilage volume, and other structural changes in symptomatic knee osteoarthritis patients with low Vitamin D could shed light on its efficacy.

In an April 2 presentation titled, “Vitamin D Supplementation for the Management of Knee Osteoarthritis: A Randomized Controlled Trial,” Changhai Ding, M.D., from the University of Tasmania in Australia, discussed whether supplementing Vitamin D over two years can lessen knee osteoarthritis symptoms.

“Vitamin D supplementation over two years did not meet either primary endpoint. Secondary analyses suggest modest benefits on knee pain, physical function, bone marrow lesions and effusion-synovitism,” the authors wrote in the abstract.

In a multicenter trial, 413 symptomatic knee osteoarthritis patients – average age 63 and 51 percent women – who also had low 25-hydroxyvitamin D (25OHD) (12.5-to-60 nmol/L) participated in a placebo-controlled study. They either received 50,000 IU Vitamin D3 (n=209) or a placebo (n= 204) for two years. Primary outcomes included a change in tibial cartilage volume on MRI and in pain levels. Secondary outcomes were knee pain, WOMAC function, cartilage defects, bone marrow lesions (BML), and joint effusion-synovitis on MRI.

Vitamin D levels did increase in the 25OHD, and the group did have less cartilage volume loss and more pain reduction, -3.44 percent and -4.23 percent and -49.9 and -35.1, respectively, even though the differences weren’t significant. After a second analysis, the 25OHD group experienced greater knee pain improvement. However, there was no significant difference in tibiofemoral cartilage defect changes or BMLs.

Fewer 25OHD participants had an increase in BMLs, and they had less increase in effusion-synovitis volume than the placebo group (0.26 ml and 2.20 ml). The 25OHD group also had a significantly higher chance of achieving a minimal clinical important improvement in total and suprapatellar effusion-synovitis.

To read the article at its original location: http://www.rheumatologynetwork.com/OARSI2016/only-minimal-pain-relief-vitd-knee-pain

 

April 13, 2016 Posted by | Healthcare | , , | Leave a comment

OA Pathology Linked to New Biomarkers

Published on the April 5, 2016, Rheumatology Network website

By Whitney L.J. Howell

Spanish researchers have uncovered evidence that may be indicative of solid biomarkers for osteoarthritis (OA). Researchers reported their findings at the OARSI 2016 World Congress held in Amsterdam this month.

To date, no such biomarkers exist, but this group of researchers found six potential biomarkers, with one rising to the top as an early prognostic biomarker in osteoarthritis. Without a reliable biomarker in osteoarthritis, making a diagnosis can be difficult.

“We have defined an interesting panel of six biomarker candidates. Some of them (ITIH1 and C3) can also distinguish between OA patients and patients from other rheumatic diseases. Moreover, we have found S100A6 could be a novel potential early and prognostic biomarker in OA,” researchers wrote in the abstract.

To identify whether reliable protein biomarkers could be found, the research team conducted a large-scale study to pinpoint potential knee osteoarthritis indicators.

In an April 1 presentation titled “Identification of a Serum Protein Biomarker Panel for the Diagnosis of Knee Osteoarthritis,” Luca Lourido from the rheumatology division of Hospital Universitario de A. Coruna in Spain, discussed using broad-scale profiling of protein levels in serum to discover novel osteoarthritis biomarkers.

The team applied antibody suspension bean arrays to profile serum knee osteoarthritis samples with different Kellgren-Lawrence (KL) scores (n=288) and compared them to rheumatoid arthritis (n=288), psoriatic arthritis (PsA) (n=288), and healthy controls (n=96). Protein profiles were obtained using 174 antibodies from the Human Protein Atlas, targeting 78 proteins.

Forty-six proteins were further profiled in a focused-bead array to validate results in an independent cohort of serum samples of osteoarthritis patient (n=196), RA (n=192), PsA (n=192), and healthy controls (n=92). Samples were selected based on previous internal protein profile studies. Protein profiles were adjusted for sex, age, and body mass index.

Compared to healthy controls four proteins had elevated levels in serum: S100 calcium binding protein A6, leptin, Complement 3, and Inter-Alpha-Trypsin Inhibitor Heavy Chain. Healthy controls had two elevated proteins – apolipoprotein A1 and vitamin D-binding protein. S100A6 was also found at high levels in KL scores compared to healthy controls in both sample cohorts.

Through this profiling, researchers identified a panel of six biomarker candidates that allow for distinguishing samples from healthy individuals and those with osteoarthritis or other rheumatic diseases. Alterations of these proteins could provide new serum biomarkers that could expand the knowledge of OA biomarkers and lend a better understanding of osteoarthritis pathology.

To read the article at its original location: http://www.rheumatologynetwork.com/OARSI2016/oa-pathology-linked-new-biomarkers

April 13, 2016 Posted by | Healthcare | , , , , , , , | Leave a comment

   

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