The promise of precision medicine may be turning into reality for people with rheumatoid arthritis. For the first time, scientists from a Northwestern University study used genetic profiling of joint tissue to better understand which drugs worked best in certain patients.
The results point to a way for doctors to more accurately prescribe drugs for patients using the genetic markers of their unique form of RA. Such an advancement would reduce the time and money currently spent on months of ineffective therapy. Experts estimate that $2.5 billion a year is wasted on drug therapy that doesn’t work.1,2
The paper was published in the journal Arthritis & Rheumatology in late May 2018.
Drug therapy roulette
Currently, before prescribing medicine for RA, doctors take blood samples to determine what antibodies a patient is producing against themselves, look at how swollen their joints are, and which medications they’re already taking.
Of the many drugs available, doctors essentially must guess which one their patient should try for 12 weeks. If they don’t respond, the patient moves on to another drug in search of the right biologic therapy. Unfortunately, this diagnostic technique has proven frustrating for patients and ineffective in treating RA.
This new study followed 41 rheumatoid arthritis patients in total; 30 from Northwestern and 11 from the University of Alabama at Birmingham; Washington University, Columbia University, Mayo Clinic and University of Michigan.
Scientists from the six sites employed ultrasound-guided therapy to take a tissue biopsy of the affected joint, a relatively new minimally invasive technique in use in Europe for about six years. Subjects reported little side effects to the procedure.
The researchers then analyzed the joint tissue of their 41 subjects, separating out different immune cell populations. The scientists focused on macrophages, which are overactive in rheumatoid arthritis. These cells are responsible for producing the toxic, inflammatory proteins that destroy a person’s joints. Drug therapy works by removing the protein molecules secreted by the macrophages that cause joint damage.
Collecting genetic signatures
After collecting the biopsied joint tissue, the scientists separated the patients into two groups who shared certain aspects of a genetic profile. Next, they identified who within the two groups had joints that were getting better and which drug therapies they were taking.
Then, they identified a gene sequence found in patients with early disease. This was helpful because the earlier a patient is treated, the more effective the therapy tends to be. The idea is that once a person’s genetic sequence is known, the more likely doctors are able to predict which specific drug will give them the best response. In all, the scientists were able to identify different subpopulations of patients and six new genetic modules associated with RA disease activity and therapy.
Another study has already begun. This time, the scientists are taking joint biopsy tissue as the patient begins a new drug therapy and again six weeks later. They hope to discover which gene sequences clearly predict which patients respond to certain drugs. The researchers expect this precision medicine technique will soon become the standard of care for all RA patients.
This study was funded by the National Cancer Institute, National Institutes of Health, Pfizer, United States–Israel Binational Science Foundation, Rheumatology Research Foundation, Arthritis National Research Foundation, and Northwestern University.
Northwestern University. "Rheumatoid arthritis meets precision medicine: For first time scientists on way to predicting which drugs will help patients based on genetic profile of disease." ScienceDaily. 19 March 2018. https://www.sciencedaily.com/releases/2018/03/180319124232.htm. Accessed May 30, 2018.
Mandelin, AM, et al. Transcriptional Profiling of Synovial Macrophages Using Minimally Invasive Ultrasound‐Guided Synovial Biopsies in Rheumatoid Arthritis. Arthritis and Rheumatology. https://onlinelibrary.wiley.com/doi/abs/10.1002/art.40453