Navigation Links
Potential anti-TNF response biomarker identified
Date:6/12/2014

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
eularpressoffice@cohnwolfe.com
44-078-801-73209
European League Against Rheumatism
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... June 25, 2016 , ... Austin residents seeking Mohs surgery services, can now ... and to Dr. Russell Peckham for medical and surgical dermatology. , Dr. Dorsey brings ... The selective fellowship in Mohs Micrographic Surgery completed by Dr. Dorsey was under the ...
(Date:6/25/2016)... Oklahoma (PRWEB) , ... June 25, 2016 , ... ... both athletes and non-athletes recover from injury. Recently, he has implemented orthobiologic procedures ... Oklahoma City area —Johnson is one of the first doctors to perform the ...
(Date:6/24/2016)... ... June 24, 2016 , ... June 19, 2016 is World Sickle ... chronic pain and the benefits of holistic treatments, Serenity Recovery Center of ... Sickle Cell Disease. , Sickle Cell Disease (SCD) is a disorder of the red ...
(Date:6/24/2016)... ... June 24, 2016 , ... Comfort Keepers® of San Diego, ... and the Road To Recovery® program to drive cancer patients to and from their ... to ensure the highest quality of life and ongoing independence. Getting to and ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... client, The Grove Investment Group (TGIG), has initiated cultivation and processing operations at ... Las Vegas and Pahrump, Nevada. , Puradigm is the manufacturer of a complete ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016 Dehaier Medical Systems ... "Company"), which develops, markets and sells medical devices and ... , signed a strategic cooperation agreement with Hongyuan Supply ... Supply Chain") on June 20, 2016, to develop Dehaier,s ... strategic cooperation agreement, Dehaier will leverage Hongyuan Supply Chain,s ...
(Date:6/24/2016)... Mass. , June 24, 2016   Pulmatrix, ... pharmaceutical company developing innovative inhaled drugs, announced today that ... Russell Investments reconstituted its comprehensive set of ... "This is an important milestone for Pulmatrix," ... will increase shareholder awareness of our progress in developing ...
(Date:6/23/2016)... Research and Markets has announced the addition of the ... report to their offering. ... failure, it replaces the function of kidneys by removing the ... the treatment helps to keep the patient body,s electrolytes such ... Increasing number of ESRD patients & substantial healthcare expenditure on ...
Breaking Medicine Technology: