Treatment options for VEXAS syndrome
| Treatment . | Effectiveness . | Considerations . |
|---|---|---|
| Glucocorticoids | Highly effective, but difficult to taper off in the absence of other therapies, and treatment-free remissions are rare4 | Infection risk; chronic glucocorticoid therapy–associated effects such as posterior subcapsular cataracts, hyperglycemia and dyslipidemia, adrenal insufficiency, and osteopenia |
| Older rheumatologic DMARDs (eg, methotrexate), anti-B-cell therapies (eg, rituximab) | Low rate of effectiveness | Cytopenias and opportunistic infection risk; anti-B-cell therapies can worsen lymphopenia |
| Anticytokine or other immunomodulatory therapies (eg, interferon, anti-TNF antibodies, IL-6 inhibitors such as tocilizumab, IL-1 inhibitor anakinra) | Anecdotes of favorable responses in inflammatory symptoms5 | Infection risk; report of a severe injection site reaction with anakinra; no effect on cytopenias, if present |
| JAK inhibitors | Benefit reported with ruxolitinib6 and upadcitinib,7 including ability to decrease or discontinue corticosteroids; ongoing trials of pacritinib | Cytopenias (eg, worsening of anemia) and potential infection risk |
| DNA methyltransferase inhibitors (azacitidine, decitabine) | High response rate with azacitidine in both inflammatory and hematologic findings regardless of cytopenias, as described by the FRENVEX group and in other series | Cytopenias, infections (likely due to concomitant or prior use of immunosuppressants); potential reimbursement barriers when coding VEXAS syndrome rather than MDS; discontinuation results in prompt relapse, but patients may respond again with therapy reinitiation; few reported data on decitabine so far |
| Allogeneic HCT | Can be curative, but most patients with VEXAS syndrome have features of lower-risk MDS and would not typically undergo transplant; encouraging experience with reduced-intensity conditioning approaches | Transplant-associated morbidity and mortality; access barriers and high cost |
| Treatment . | Effectiveness . | Considerations . |
|---|---|---|
| Glucocorticoids | Highly effective, but difficult to taper off in the absence of other therapies, and treatment-free remissions are rare4 | Infection risk; chronic glucocorticoid therapy–associated effects such as posterior subcapsular cataracts, hyperglycemia and dyslipidemia, adrenal insufficiency, and osteopenia |
| Older rheumatologic DMARDs (eg, methotrexate), anti-B-cell therapies (eg, rituximab) | Low rate of effectiveness | Cytopenias and opportunistic infection risk; anti-B-cell therapies can worsen lymphopenia |
| Anticytokine or other immunomodulatory therapies (eg, interferon, anti-TNF antibodies, IL-6 inhibitors such as tocilizumab, IL-1 inhibitor anakinra) | Anecdotes of favorable responses in inflammatory symptoms5 | Infection risk; report of a severe injection site reaction with anakinra; no effect on cytopenias, if present |
| JAK inhibitors | Benefit reported with ruxolitinib6 and upadcitinib,7 including ability to decrease or discontinue corticosteroids; ongoing trials of pacritinib | Cytopenias (eg, worsening of anemia) and potential infection risk |
| DNA methyltransferase inhibitors (azacitidine, decitabine) | High response rate with azacitidine in both inflammatory and hematologic findings regardless of cytopenias, as described by the FRENVEX group and in other series | Cytopenias, infections (likely due to concomitant or prior use of immunosuppressants); potential reimbursement barriers when coding VEXAS syndrome rather than MDS; discontinuation results in prompt relapse, but patients may respond again with therapy reinitiation; few reported data on decitabine so far |
| Allogeneic HCT | Can be curative, but most patients with VEXAS syndrome have features of lower-risk MDS and would not typically undergo transplant; encouraging experience with reduced-intensity conditioning approaches | Transplant-associated morbidity and mortality; access barriers and high cost |
Many relevant case reports and series could not be cited here because of limitations on reference number.
DMARD, disease-modifying antirheumatic drug; TNF, tumor necrosis factor.