First ACR Guidance Statement for VEXAS Released

Dr. David Beck

“When you start a second medication, taper the steroids slowly and cautiously, because patients can have acute inflammatory episodes from rapid tapers,” says Dr. Beck. Patients are rarely able to get off steroids completely, at least with current treatments from the rheumatology armamentarium; some patients cannot decrease their steroid dose at all, although steroid-sparing medications may improve quality of life.

Rheumatologists should coordinate with hematology for management of such issues as cytopenias and MDS. Allogeneic hematopoietic stem cell transplantation can provide a potential curative option for select patients.

Azacitidine, a hypomethylating agent often used in certain blood cancers and in MDS, is another management option for hematologic manifestations, as it can reduce numbers of the abnormal clonal cells. A recent retrospective study found that azacitidine helped reduce the frequency of clones with the UBA1 mutation, improving not only hematologic responses but also inflammatory findings.³

“I think that a lot of future work will go into understanding when and how we should use azacitidine more broadly in VEXAS,” says Dr. Beck. “VEXAS has more hematologic in­volvement than a classic rheumatic condition, but also more opportunity for treatment using medications outside of those already used in rheumatology.”

VEXAS patients are at increased risks for both infections—from the disease itself and from immunosuppressive treatments—as well as thromboembolic disease. Thus, the guidance document also highlights the need for considering prophylaxis for both (e.g., viral prophylaxis or prophylaxis for such organisms as pneumocystis or mycobacteria).

The guidance document also highlights another key management concern: both infection and thrombo­embolic disease can mimic disease flares. Dr. Koster adds that sequential treatments can sometimes help establish the true cause, if unclear. “First, initiate treatment for what you most suspect, then assess,” he says. “If you use anti­microbials and prednisone simultaneously, it’s very hard to know which one led to the benefit.”

For more information about other aspects of the diagnosis and manage­ment of VEXAS, including detailed recommendations on screening for UBA1 mutations and diagnosis of MDS in patients with VEXAS, see the full guidance document (https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.43287).

Moving Forward

Although the disease is rare, rheuma­tologists may encounter more of these patients in the future. “We think the vast majority of patients aren’t diagnosed now,” says Dr. Beck, “but UBA1 is going to be added to more next-generation sequencing panels for anemia or cytopenias, and many patients will be diagnosed through this kind of broad testing.”