The RhEumatoid Arthritis SynOvial tissue Network (REASON) Study
Today, there are many treatments for patients with rheumatoid arthritis (RA), yet there is little information to help identify which therapy will work for a particular patient. Therefore, the current standard is a costly and time-consuming trial-and-error process of one medication after another, which creates a tremendous burden on the patient.
Thus, there is an overwhelming need to develop new testing to predict response to treatment. Unfortunately, markers that indicate sensitivity or resistance to a particular medication are lacking. For the most part, researchers have so far utilized blood testing without success. Recent research has suggested that the joint lining itself, the tissue that is damaged by RA, may hold the secret. Until now, researchers have obtained this tissue by taking biopsies during arthroscopic surgery or joint replacement, but this requires a trip to an OR and these patients typically have very advanced disease which does not reflect the behavior of RA at the time when therapeutic decisions need to be made -- prior to progressive joint damage.
There is a potential solution. Over the past decade, ultrasound technology has significantly advanced and is now widely used by rheumatologists, especially in Europe where ultrasound-guided joint biopsies have become important in research. To bring this technology to the United States, we have assembled a consortium of leading academic rheumatology groups, led by Northwestern University, including the University of Alabama at Birmingham, Columbia University, Mayo Clinic, Washington University, and University of Michigan to form the RhEumatoid Arthritis SynOvial tissue Network (REASON).
We are now successfully performing minimally-invasive ultrasound-guided joint biopsies on American patients who have active RA, and the samples from these patients are being studied with some of the newest and most advanced testing in existence. We hope with this testing to identify a marker within the joint lining which will predict medication outcomes and bring the era of trial-and-error medication switching to an end.
Rheumatoid arthritis (RA) is a chronic disease involving inflammation of the joints, resulting in pain, swelling, stiffness, and loss of function. It is different from osteoarthritis, the most common arthritis, which often comes with age. RA can strike any joint, but most commonly involves the small joints in the hands and wrists. Rheumatoid arthritis also may have effects on other organs, such as the heart and lungs. The exact cause of rheumatoid arthritis is not known, but we do know that it is an autoimmune disorder, which means the body's immune system attacks its own healthy cells and tissues. About 70 percent of persons with rheumatoid arthritis are women, and the disease most often starts between the ages of 30 and 50.
If you choose to participate in this study and meet entry criteria, there may be up to three parts to your participation and we will also review your medical chart.
1). You will undergo a minimally-invasive ultrasound-guided tissue biopsy. In this procedure, we will sterilize the skin over your joint, and then inject numbing medicine into the joint. After that, a needle or small grasping device called a forceps will be inserted into the joint so that we can get several small pieces of synovial tissue (the lining of the joint that is involved with rheumatoid arthritis) from the inside of the joint. The biopsy will be done using ultrasound to guide the placement of the needle or forceps. The ultrasound machine uses a probe on the surface of the skin, which is able to use sound waves to give a picture of the tissue inside the joint. In this way, the study doctor can be sure that the needle or forceps is placed so that it gets tissue from an inflamed area of the joint. After the procedure is complete, you will probably not require more than an ordinary adhesive bandage over the site of the biopsy. Your participation will last for the duration of the biopsy, which should take about one hour. You will be given $200 by check the biopsy.
2). Additionally, you will have blood drawn for research purposes. This can be collected along with a normally scheduled blood draw or, if this is not convenient for you, by a nurse or doctor involved with the study. This blood will be compared with the tissue taken from your joint, and blood cells will be isolated for genetic analysis. The specific tests that will be performed will be determined following the analysis of the matched synovial tissue. Your participation in this part of the study would last for the length of the blood draw, which would take 5-10 minutes.
3) Finally, you may be asked to come for a second visit 12 weeks after the biopsy, in order to have a second biopsy and a second blood draw. The purpose of this would be to determine the effect of your arthritis treatment on the tissue and the blood. This visit would take about 60-90 minutes.
The risks associated with the tissue biopsy include infection, bleeding into the joint, temporary joint pain after the biopsy, and a bruise or small scar at the site of the needle insertion. In very rare cases, people might have an allergic reaction to the numbing medicine or the skin cleanser. The allergic reaction could include rash/hives, flushing of the face, itching, wheezing and tightness in the throat. The risks associated with the blood draw include pain, a bruise at the site of draw, inflammation of the vein, and infection. Every care will be taken to avoid these complications.
Harris R. Perlman, PhD
Richard M. Pope, MD
Eric M. Ruderman, MD
Arthur M. Mandelin, MD, PhD
Carla Cuda, PhD
As part of the REASON study, the division is proud to host trainings in synovial tissue biopsy. Please view our videos of our December 2016 training event.
Synovial Biopsy Training Video: Study Coordinator
Speaker: Arthur Mandelin, MD, PhD, Assistant Professor
Synovial Biopsy Training Video: Biopsy Proceduralist
Speaker: Emily Bacalao, Study Coordinator
To connect with Northwestern Medicine clinical resources, see the Division of Rheumatology’s Northwestern Medicine site.