Navigation Links
Potential anti-TNF response biomarker identified

DNA methylation has been identified as a potential biomarker of response to etanercept and adalimumab in patients with rheumatoid arthritis (RA) according to preliminary results from one of the largest methylome-wide investigations of treatment response to anti-TNF therapies.1 These data, presented today at the European League Against Rheumatism Annual Congress (EULAR 2014), bring clinicians a step closer to being able to personalise a patient's treatment pathway.

Anti-TNF therapies have proved a huge advance for the treatment of rheumatoid arthritis and have transformed the treatment of inflammatory arthritis for millions of people around the world. However, only 20-40% of patients achieve a good response according to EULAR criteria.2

"It can take several years to identify the most effective treatment for an RA patient. This is not only costly in terms of the financial burden, but also in terms of patient outcomes and the irreversible joint damage that is being done," said Amy Webster, University of Manchester, United Kingdom. "Because of this, the identification of biomarkers that can predict a patient's response to a treatment is an important area of research which will allow the most effective treatment for each patient to be identified early in the course of the disease."

She continued, "Based on recent studies showing a role for epigenetics in RA and other autoimmune disorders, we hypothesised that epigenetic changes, such as DNA methylation, may provide potential biomarkers of response to anti-TNFs."

RA is a chronic systemic disease that affects the joints, connective tissues, muscle, tendons, and fibrous tissue. A disabling condition that often causes pain and deformity, symptoms of RA tend to appear between the ages of 20 and 40. The prevalence of RA globally varies between 0.3% and 1% and is more common in women and in developed countries. Within 10 years of onset, at least 50% of patients in developed countries are unable to maintain a full-time job.3 1In this study, patients were selected from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) longitudinal cohort based on having an extreme response phenotype after three months of treatment with etanercept or adalimumab. Of the patients in the study, 36 patients were good responders to etanercept and 45 to adalimumab as defined by having an endpoint of DAS28<2.6. Poor responders to etanercept (35) and adalimumab (27) were defined by having an improvement of <0.6 or between 0.6-1.2 with an endpoint DAS28 of >5.1.

DNA from each patient was sampled before therapy was initiated. Following bisulfite conversion of the DNA, an epigenome-wide association study was conducted using the HumanMethylation450 BeadChip (Illumina) to determine unmethylated versus methylated cytosines within the DNA. The results from each drug were analysed separately and together using the minfi package in R and probes with a detection-p value > 0.01 were removed. Differentially methylated positions between responders and non-responders were identified using the F-test following quantile normalisation.

In the etanercept study, four CpG* sites showed differential DNA methylation that passed a false discovery rate of 0.05, while in the adalimumab study less significant results were observed. The most differentially methylated position in etanercept patients mapped to the LRPAP1 gene (p=1.46x10-8). This gene encodes a chaperone of low density lipoprotein receptor-related protein 1 (LRP1) which is known to influence TGF-β activity. Technical validation of methylation at this site by pyrosequencing showed very good correlation (Spearmans r=0.8). In the adalimumab patients, the most differentially methylated position maps to the PDZD8 gene. Joint analysis of the two drugs together identified a differentially methylated region overlapping the CRYZ and TYW3 genes, which have previously been associated with inflammation and Type 2 diabetes.4

Contact: EULAR Press Office
European League Against Rheumatism

Related medicine news :

1. Trial uncovers potential dangers of chemotherapy regimen for bladder cancer patients
2. Molecule linked to aggressive pancreatic cancer offers potential clinical advances
3. Cancers potential on-off switch
4. Study points to potential revision of treatment guidelines for bleeding ulcers
5. How bacteria exploit proteins to trigger potentially lethal infections
6. Microfluidic technology reveals potential biomarker for early pancreatic cancer
7. Researchers identify potential new strategy to treat ovarian cancer
8. Revolutionary metamaterial has potential to reshape neurosurgery
9. Scientists identify cancer specific cell for potential treatment of gastric cancer
10. CT measures potentially dangerous arterial plaque in diabetic patients
11. Live cell imaging reveals distinct alterations of subcellular glutathione potentials
Post Your Comments:
(Date:10/13/2017)... ... October 13, 2017 , ... As health professionals work to improve their approach ... patient is doing more than filling out a survey; in many cases health professionals ... emphasis in health care and research on the importance of active engagement with patients ...
(Date:10/13/2017)... , ... October 13, 2017 , ... The American Board ... become its next President and Chief Executive Officer, succeeding Dr. James C. Puffer upon ... beginning July 1, 2018 until Dr. Puffer’s retirement at the end of 2018. Upon ...
(Date:10/13/2017)... ... October 13, 2017 , ... PurhealthRX , a leading Health ... technology. Applying the Purzorb™process to full spectrum CBD oil will revolutionize the rapidly growing ... form that can be easily incorporated into liquid products, while reducing costs to end ...
(Date:10/13/2017)... ... ... Lori R. Somekh, founder of the Law Office of Somekh & ... and special needs planning attorneys. “Membership in ElderCounsel helps our office remain up to ... with elder law attorneys nationwide,” said Somekh. , ElderCounsel was founded ...
(Date:10/13/2017)... OBISPO, Calif. (PRWEB) , ... October 13, 2017 , ... ... or dementia. However, many long-term care insurance companies have a waiver for care if ... the 90-day elimination period, when the family pays for care, is often waived, so ...
Breaking Medicine News(10 mins):
(Date:9/28/2017)... Cohen Veterans Bioscience and Early Signal Foundation announce a ... sensors for real-time monitoring of patients with trauma-related and ... focused on disruptive health solutions for rare disorders and ... record and integrate behavioral, cognitive, physiological and contextual data. ... ...
(Date:9/25/2017)... PROVIDENCE, R.I. , Sept. 25, 2017 /PRNewswire/ ... immunogenicity assessment, vaccine design, and immune-engineering today announced ... focused on the development of personalized therapeutic cancer ... and has provided exclusive access to enabling technologies ... MSc Eng., MBA will lead EpiVax Oncology as ...
(Date:9/19/2017)... venture-backed medical device company developing a non-invasive, robotically assisted, platform therapy that uses pulsed sound ... ... Jim Bertolina, PhD ... Tom Tefft ... device executive Josh Stopek , PhD, who has led R&D and business development teams ...
Breaking Medicine Technology: