As a group of rare diseases for which current scientific knowledge is incomplete, vasculitis represents a challenge in both diagnosis and treatment. Although the overall quality of research and care for vasculitis has improved significantly, these advances have not equally affected the individual conditions.
The identification of antineutrophil cytoplasmic antibodies (ANCA) several decades ago has driven research toward ANCA-associated vasculitides, such as granulomatosis with polyangiitis or Wegener’s granulomatosis. This research, which includes randomized clinical trials, has generated a substantial knowledge base and increased therapeutic options for these conditions. Conversely, conditions like Takayasu’s arteritis, which has been less of a research focus, have been managed with a relative dearth of evidence-based guidance.
“ANCA is a good story of how discovery of an autoantibody propelled the field forward in a lot of different ways,” Peter Grayson, MD, head of the Vasculitis Translational Research Program at the National Institute for Arthritis and Musculoskeletal and Skin Diseases, told Healio Rheumatology. “I think those kinds of discoveries are lacking in some of the other types of vasculitis. Overall, though, there has been progress in how vasculitis patients in general are cared for. A lot of that is due to the fact that we’re becoming more experienced in the use of immunosuppressant medications to control inflammatory diseases.”
Grayson spoke to Healio Rheumatology about the different types of vasculitis, the varying rates with which the science has evolved about these conditions and the promising new studies on this complicated family of diseases.
Healio Rheumatology: You mentioned a lack of evidence to guide treatment decisions in Takayasu’s arteritis. Does this mean physicians make decisions based on anecdotal evidence for this condition?
Grayson: A lot of treatment decisions in Takayasu’s arteritis are made based on the physician’s experience with the disease, and there is less evidence to guide decision making. Encouragingly, at the American College of Rheumatology (ACR) Annual Meeting, we’re starting to see a lot more research into large vessel vasculitis, which includes Takayasu’s arteritis and giant cell arteritis. In past years, the vasculitis portion of the conference was more dominated by research into ANCA-associated vasculitis, but there is starting to be more research into large vessel vasculitis, which is great, because there is tremendous unmet need in those diseases.
There are a lot of themes to this research; one of the themes relates to the role that vascular imaging plays in the assessment of these patients. Clinical assessment of patients with large vessel vasculitis at the bedside is challenging. It’s sometimes hard to know if the disease is still active or in remission. We’re trying to incorporate clinical assessment with imaging-based assessment, so we can directly visualize inflammation in the blood vessel wall and get a more objective sense of what’s going on. I think a lot of those types of studies are popping up and will probably be featured at ACR Annual Meeting this year.
Healio Rheumatology: What are some of the most important recent studies on large vessel vasculitis?
Grayson: At the ACR Annual Meeting in 2016, the GiACTA trial was first presented and it’s subsequently been published in the New England Journal of Medicine. That was a trial on giant cell arteritis and it showed that tocilizumab was efficacious. It was the first convincing large randomized trial in giant cell arteritis to show that a drug other than steroids were effective. That trial helped establish a blueprint for how to conduct successful trials in large vessel vasculitis. Hopefully, more successful clinical trials will follow.
Healio Rheumatology: What direction is research taking in terms of ANCA-associated vasculitis?
Grayson: Many of the new trials in ANCA-associated vasculitis are focused on how do we keep the disease from coming back once the patient is in remission. The studies are also investigating ways to use less glucocorticoids to treat the disease. Some of the newer trial designs are trying to look at other drugs that will take the place of steroids in the treatment of ANCA-associated vasculitis.
Healio Rheumatology: What role is new diagnostic technology playing in advancing the field of vasculitis care?
Grayson: I think some of the studies that are starting to emerge are focused around the theme of molecular classification of disease. When we think about vasculitis, we traditionally group them into the size of the blood vessel that’s involved. There is small vessel vasculitis, medium vessel vasculitis and large vessel vasculitis. That’s helpful for training and teaching purposes to start to understand the many complex forms of vasculitis that exist, but it’s not helpful biologically. It doesn’t tell you what’s happening at the molecular level. It doesn’t tell you what’s driving inflammation in those different types of vasculitis.
What I would love to see is for some of the high throughput technology put to use to identify, specifically, what elements of inflammation are driving vasculitis in an individual subject. I would love to see personalized medicine approaches realized in ANCA-associated vasculitis.
Healio Rheumatology: The criteria for vasculitis have not been updated in a long time. When will new criteria be released?
Grayson: There is a diagnostic and classification study (DCVAS) being conducted, with a goal of updating classification criteria in vasculitis. The criteria that are currently in use were done in 1990. In ANCA-associated vasculitis, the criteria were developed prior to the widespread adoption of ANCA testing, so ANCA are not incorporated into the criteria. Draft versions of new criteria in three types of ANCA-associated vasculitis are being debuted on the last day of the ACR Annual Meeting. This work is the result of an international collaborative effort involving more than 100 countries and more than 6,000 patients. As such, it is the largest study ever conducted in vasculitis. We hope these new criteria will be useful to helping advance clinical research in these diseases for many years to come. -by Jennifer Byrne
For more information:
Peter Grayson, MD, can be reached at 9000 Rockville Pike,Bethesda, MD 20892; email: firstname.lastname@example.org.
Disclosure: Grayson reports no relevant financial disclosures.