Better targeting of therapies could improve arthritis treatments
30 Apr 2014
Scientists have identified four subtypes of rheumatoid arthritis, and have demonstrated that they respond differently to available treatments for the condition. The research, published in the journal Arthritis & Research Therapy, could improve treatments and targeting of treatments for the condition and potentially for other autoimmune disorders.
There is currently no cure for rheumatoid arthritis; most treatments focus on alleviating the symptoms. Not all rheumatoid arthritis is the same so different people with the condition should receive different treatments. Researchers from Genentech performed genomic analysis of tissue from 69 RA patients as well as analysis of 198 blood samples from patients who participated in a randomized control trial. The tissue sample analysis identified four subtypes of rheumatoid arthritis; two based on inflammation – lymphoid and myeloid, a third based on activation of fibroblasts, and a fourth based on a combination of the other three. The researchers then identified biomarkers in the blood samples that reflected the genes expressed in the tissue.
Rheumatoid arthritis is an autoimmune disease that affects 1.3 million people in the US alone. Symptoms include the swelling of joints, stiffness, fatigue and generally feeling unwell. The condition affects people in different ways, which makes it tricky to predict how it will develop. Predicting how people respond to treatments is not possible and most treatment pathways are based on trial and error.
Treatment options are largely based on drugs such as painkillers, anti-inflammatories and steroids. More recently, treatments have started to focus on the use of a new class of drugs called biologics, such as tumor necrosis factor inhibitors (anti-TNFs) and interleukin inhibitors (anti-ILs) such as anti-IL-6 therapies. These drugs can be effective but do not work for everyone.
When the researchers analyzed serum samples from patients involved in a clinical trial assessing both anti-TNF and anti-IL-6 therapies, they found that the patients responded differently depending on which subtype of rheumatoid arthritis they had. Those with the subtype based on the inflammation of myeloid tissue had a high presence of the biomarker sICAM1 in blood serum and showed a better response to anti-TNF therapy. In contrast, those who had inflammation of lymphoid tissue had raised levels of the biomarker CXCL13 and responded well to anti-IL-6 therapy.
For this to be of use in the clinical setting, further work needs to be done on strengthening the algorithm that classifies patients and more biomarkers need to be identified.
Senior author of the study, Michael Townsend, says: “A better appreciation of the underlying heterogeneity of rheumatoid arthritis will be important for physicians as they make treatment decisions for their patients, as well as for future drug discovery for RA where focus could be made on patients subpopulations where existing drugs are not effective.”
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Notes to Editor
1. Neural Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics
Glynn Dennis Jr, Cécile TJ Holweg, Sarah K Kummerfeld, David F Choy, A Francesca Setiadi, Jason A Hackney, Peter M Haverty, Houston Gilbert, Wei Yu Lin, Lauri Diehl, Sally Fischer, An Song, David Musselman, Micki Klearman, Cem Gabay, Arthur Kavanaugh, Judith Endres, David A Fox, Flavius Martin and Michael J Townsend
Arthritis Research & Therapy 2014, 16:R90
Article available at journal website here.
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2. Arthritis Research & Therapy is an international, peer-reviewed online journal, publishing original research, reviews, commentaries and reports. The major focus of the journal is on cellular and molecular mechanisms of arthritis, musculoskeletal conditions and systemic autoimmune rheumatic diseases and translation of this knowledge into advances in clinical care.
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