Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises a group of autoimmune disorders characterized by the inflammation of small and medium-size blood vessels.1 This disease can affect various organs and systems, such as the kidneys, lungs, skin, heart, and gastrointestinal and nervous systems, and it can lead to serious complications if left untreated.2,3
The current treatment of AAV involves 2 main phases: induction of remission and maintenance of remission. It relies on a combination of therapies to suppress the immune system, and consequently reduce inflammation and control organ damage.4 To induce remission, high doses of glucocorticoids are typically combined with Cytoxan® (cyclophosphamide) or Rituxan® (rituximab). For maintenance therapy, Rituxan, methotrexate, Imuran® (azathioprine), or CellCept® (mycophenolate mofetil), sometimes in combination with reduced doses of glucocorticoids, are recommended.1
Glucocorticoids, used as the first-line therapy in AAV, reduce inflammation rapidly.1,4,5 High doses of glucocorticoids are usually given initially for rapid disease control, followed by a gradual taper to minimize side effects. However, the optimal dose, taper regimen, and duration of treatment are not clear.4 Traditionally, patients with life-threatening disease receive 1 to 3 g of intravenous methylprednisolone, followed by oral prednisone at 1 mg/kg per day.6
Glucocorticoids are associated with several adverse effects, including osteoporosis, diabetes, hypertension, psychosis, insomnia, skin thinning, early cataracts, glaucoma, bruising, and increased risk of infection.1
Read more about AAV guidelines
Cytoxan was one of the first drugs for which clear clinical evidence of remission induction and mortality reduction in AAV became available.1,4 Cyclophosphamide is an alkylating agent that inhibits DNA replication.6 The combination of Cytoxan and glucocorticoids has been used for several decades and is a current standard of care for remission induction in patients with severe disease.1,5
Although effective, Cytoxan is associated with risks of infertility, urotoxicity (eg, transitional cell carcinoma of the bladder), and lymphoma.4,6 In a study involving 524 patients with AAV who received glucocorticoids and Cytoxan, the 1-year probability of death was 11.1%, and 59% of the deaths in the study were associated with adverse effects of the medication.1 Toxicity can be reduced by decreasing the dose in older patients.4
Read more about AAV risk factors
Rituxan, a chimeric anti-CD20 monoclonal antibody, was studied as an alternative to Cytoxan.4,6 Approval of this drug for AAV therapy was based on the results of 2 pivotal clinical trials.7,8
Rituxan is used as an alternative to Cytoxan for patients who have severe disease or who cannot tolerate Cytoxan. It has been shown to be effective in inducing and maintaining remission in AAV, with fewer side effects than Cytoxan.1,4 The most common side effects of Rituxan are infusion reaction, increased risk of infection, arthralgia, and skin rash.4
Read more about AAV treatment
Long-term maintenance therapy in AAV can be achieved with immunosuppressants other than Rituxan, such as Imuran, methotrexate, and CellCept. These therapies can sometimes be combined with low-dose glucocorticoids.1 CellCept has been shown to be effective in inducing remission in patients without life-threatening disease and in maintaining remission in patients with contraindications to or adverse effects of Imuran or methotrexate.4,6 Imuran has been shown to be more effective for maintenance than CellCept.1 Methotrexate can be given to patients without severe disease; however, long-term outcomes are inferior to those with Cytoxan.5
Methotrexate can cause infection, hepatotoxicity, gastrointestinal symptoms, myelosuppression, and teratogenicity. Imuran is associated with an increased risk of neoplasia and cytopenia. CellCept can cause infections and is associated with an increased risk of neoplasia.4
Read more about AAV complications
Tavneos® (avacopan), a selective inhibitor of the complement C5a receptor C5aR1, was recently approved as an add-on treatment for severe, active AAV.9 This small molecule blocks C5a-mediated neutrophil activation and migration.9 Tavneos was approved by the US Food and Drug Administration (FDA) in 2021 following positive results of the double-blind, randomized phase 3 clinical trial ADVOCATE (NCT02994927), which demonstrated the efficacy of Tavneos in inducing and sustaining AAV remission when used in combination with Cytoxan followed by Imuran, or in combination with Rituxan.10
Adverse effects of Tavneos include hepatotoxicity, life-threatening hepatitis B reactivation, serious infection, and hypersensitivity reactions.9
Read more about AAV clinical trials
Nucala® (mepolizumab) is an anti-interleukin 5 humanized monoclonal antibody with demonstrated effects on allergic manifestations.5,11 In a randomized, controlled clinical trial, Nucala was administered by subcutaneous injection at 300 mg every 4 weeks and was shown to prolong remission and make it possible to decrease the dose of steroids used. These results led to the approval of Nucala by the FDA in 2017 as add-on therapy for adult patients with relapsed or refractory eosinophilic granulomatosis with polyangiitis (EGPA), one of several types of AAV.11
Adverse effects of Nucala include headache, sinusitis, nasopharyngitis, upper respiratory tract infection, arthralgia and myalgia, abdominal pain, infusion reaction, pruritus, and eczema.11
Read more about AAV experimental therapies
1. Koening CL, von Hennigs I. Antineutrophil cytoplasmic antibody (ANCA) vasculitis: pathophysiology, diagnosis, and the evolving treatment landscape. Am J Manag Care. 2021;27(15 Suppl):S267-S276. doi:10.37765/ajmc.2021.88746
2. ANCA-associated vasculitis. GARD–Genetic and Rare Diseases Information Center. Accessed February 27, 2022.
3. Koike H, Nishi R, Ohyama K, et al. ANCA-associated vasculitic neuropathies: a review. Neurol Ther. 2022;11(1):21-38. doi:10.1007/s40120-021-00315-7
4. Ross C, Makhzoum JP, Pagnoux C. Updates in ANCA-associated vasculitis. Eur J Rheumatol. 2022;9(3):153-166. doi:10.5152/eujrheum.2022.20248
5. Kitching AR, Anders HJ, Basu N, et al. ANCA-associated vasculitis. Nat Rev Dis Primers. 2020;6(1):71. doi:10.1038/s41572-020-0204-y
6. Jain K, Jawa P, Derebail VK, et al. Treatment updates in antineutrophil cytoplasmic autoantibodies (ANCA) vasculitis. Kidney360. 2021;2(4):763-770. doi:10.34067/KID.0007142020
7. Jones RB, Tervaert JW, Hauser T, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010;363(3):211-220. doi:10.1056/NEJMoa0909169
8. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232. doi:10.1056/NEJMoa0909905
9. Tavneos®. Highlights of prescribing information. ChemoCentryx. Revised 10/2021.
10. A phase 3 clinical trial of CCX168 (avacopan) in patients with ANCA-associated vasculitis (ADVOCATE). ClinicalTrials.gov. December 16, 2016. Updated October 13, 2022. Accessed February 27, 2022.
11. Faverio P, Bonaiti G, Bini F, Vaghi A, Pesci A. Mepolizumab as the first targeted treatment for eosinophilic granulomatosis with polyangiitis: a review of current evidence and potential place in therapy. Ther Clin Risk Manag. 2018;14:2385-2396. doi:10.2147/TCRM.S159949
Reviewed by Harshi Dhingra, PhD, on 2/27/2023.