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Treatment

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) consists of a group of diseases including granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA). These disorders are characterized by inflammation and destruction of small blood vessels, affecting multiple organs such as the kidneys, lungs, intestines, stomach, and skin.¹

The 2 autoantibodies associated with ANCA-associated vasculitis are the perinuclear ANCAs (pANCAs) that target and bind to myeloperoxidase (MPO) within neutrophils and the cytoplasmic ANCAs (cANCAs) that target and bind to proteinase 3 (PR3) within neutrophils. Binding to the neutrophils activates the autoantibodies to attack small blood vessels throughout the body, resulting in widespread inflammation.²

Current Treatment of ANCA-Associated Vasculitis

The primary aims of treatment for ANCA-associated vasculitis include³:

Reduction of disease-related inflammation and prevention of permanent damage;
Prevention of disease relapse; and
Reduction of treatment-related toxicity and morbidity that may cause end-organ damage.

Treatment occurs in 2 phases: induction and maintenance. Induction therapy is initiated to achieve disease remission, while maintenance therapy prevents disease relapse following remission.⁴

Current immunosuppressive and anti-inflammatory treatments include glucocorticoids in various combinations with conventional or biologic therapies for induction, maintenance, and relapse therapy.^3,5 Treatment recommendations depend on disease severity and whether the patient is presenting the initial manifestation or a relapse of the condition. Targeted therapeutic agents may be developed in the future as the understanding of the pathogenesis of ANCA-associated vasculitis improves.³

Read more about AAV guidelines

Induction Therapy for ANCA-Associated Vasculitis

Controversy surrounds the optimal dosing and duration of glucocorticoid treatment for ANCA-associated vasculitis.⁵ Long-term glucocorticoid use introduces the concern of glucocorticoid-induced toxicity.⁴

Induction Therapy for Severe ANCA-Associated Vasculitis

For more severe forms of ANCA-associated vasculitis that may progress to mortality or organ failure, Solu-Medrol® (intravenous methylprednisolone) is traditionally administered at a dose of 1 to 3 g, followed by oral prednisone dosed at 1 mg/kg daily.⁵

The next step to induce remission while reducing glucocorticoid dosage usually involves the administration of Cytoxan® (cyclophosphamide) or Rituxan® (rituximab).⁵ Cytoxan, administered either intravenously or orally, is an alkylating chemotherapy agent and immunosuppressant that works by inhibiting nuclear DNA replication.⁵ Rituxan is an anti-CD20 monoclonal antibody that targets and destroys B cells.⁴

Initiation of one of these medications was found to allow successful tapering of prednisone after 5 to 6 months in over half of patients (64%) with severe ANCA-associated vasculitis, while the remaining individuals still required a dosage of 5 mg daily after 6 months.^5,6

Neither medication proved statistically superior to the other in cases of ANCA-associated vasculitis with recent initial onset; however, Rituxan may be superior for treatment of individuals with severe relapsing ANCA-associated vasculitis.^5,6 Additionally, Rituxan is often favored due to the known toxicity that may occur with Cytoxan administration (ie, bladder cancer, cytopenias, infertility, and hemorrhagic cystitis).⁴

Plasma exchange has also shown efficacy in reducing glucocorticoid dosage.⁷ Plasma exchange is intended to reduce circulating serum ANCA levels to reduce the autoimmune inflammation and damage to small blood vessels in ANCA-associated vasculitis.⁴ One trial showed the group that received plasma exchange reduced their glucocorticoid intake by 60% after 6 months, although all patients still required 5 mg of prednisone per day after 52 weeks.⁷

Tavneos® (avacopan), a selective antagonist of the C5a receptor located on neutrophils, is specifically formulated to treat ANCA-associated vasculitis. It decreases neutrophil activation against blood vessels in ANCA-associated vasculitis without suppressing the immune system.⁴ It may effectively treat the condition while reducing the likelihood of cumulative glucocorticoid toxicity and improving kidney function.⁴

Read more about AAV therapies

Induction Therapy for Nonsevere ANCA-Associated Vasculitis

Methotrexate may be selected to induce remission of nonsevere forms of ANCA-associated vasculitis. It is administered orally or subcutaneously at weekly doses of 0.3 mg/kg with a maximum dosage of 25 mg.⁴

CellCept® (mycophenolate mofetil) is an immunosuppressive medication selectively targeting lymphocytes, including neutrophils. In addition to glucocorticoids, patients with nonsevere ANCA-associated vasculitis may initially receive 2000 mg of CellCept daily, progressing to a maximum of 3000 mg daily, for induction of remission. However, the use of CellCept as an induction therapy increases the risk of relapse within the first 6 months after achieving remission.⁴

Read more about AAV risk factors

Maintenance Therapy for ANCA-Associated Vasculitis

Once remission is achieved, it is important to prevent ANCA-associated vasculitis relapse. Disease flares following remission may occur in 5% to 50% of patients on maintenance therapy and up to 80% to 90% of patients who do not receive maintenance therapy.⁴

Patients who have a history of relapse, GPA, or PR3-positive ANCA-associated vasculitis are more likely to relapse than patients with MPA or MPO-positive ANCA-associated vasculitis.⁴

Methotrexate, Rituxan, and Imuran® (azathioprine) are the most common medications used for maintenance therapy, although CellCept and Arava® (leflunomide) may also be considered.⁴ Low-dose glucocorticoids (such as 5 mg daily of prednisone) may also be used to prevent disease relapse.⁴ Imuran is correlated with higher relapse rates of ANCA-associated vasculitis than Rituxan during maintenance therapy.^5,8

Read more about AAV prognosis

Relapse Therapy for ANCA-Associated Vasculitis

Rituxan may be the preferred choice, not only as a maintenance therapy to prevent relapse, particularly in individuals with a history of frequent ANCA-associated vasculitis relapses who tolerate the drug,^5,9but also to effectively treat those with relapsing ANCA-associated vasculitis.¹⁰

Read more about AAV life expectancy

Other Potential Treatments for ANCA-Associated Vasculitis

Benlysta® (belimumab), a human monoclonal antibody that works by inhibiting B-cell activating factor, can be used as a maintenance therapy for individuals with newly diagnosed or relapsing severe ANCA-associated vasculitis, specifically GPA or MPA.⁴

Trimethoprim-sulfamethoxazole may be helpful in treating individuals with GPA who have upper airway involvement.⁴

Currently, Orencia® (abatacept), a molecule that binds to immunoglobulin G1 (IgG1) to block the action of CD28 and prevent the activation of T cells, is under investigation in a clinical trial (ABROGATE) to assess whether it is effective in achieving glucocorticoid-sparing remission of nonsevere, relapsing GPA.⁴

Read more about AAV experimental therapies

References

ANCA-associated vasculitis. Genetic and Rare Diseases Information Center (GARD). Updated February 2023. Accessed February 23, 2023.
ANCA vasculitis. UNC Kidney Center. Updated September 2018. Accessed February 23, 2023.
Lally L, Spiera R. Current therapies for ANCA-associated vasculitis. Annu Rev Med. 2015;66:227-240. doi:10.1146/annurev-med-011514-023051
Samman KN, Ross C, Pagnoux C, Makhzoum JP. Update in the management of ANCA-associated vasculitis: recent developments and future perspectives. Int J Rheumatol. 2021;2021:5534851. doi:10.1155/2021/5534851
Jain K, Jawa P, Derebail VK, Falk RJ. Treatment updates in antineutrophil cytoplasmic autoantibodies (ANCA) vasculitis. Kidney360. 2021;2(4):763-770. doi:10.34067/KID.0007142020
Stone JH, Merkel PA, Spiera R, et al; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232. doi:10.1056/NEJMoa0909905
Walsh M, Merkel PA, Peh CA, et al; PEXIVAS Investigators. Plasma exchange and glucocorticoids in severe ANCA-associated vasculitis. N Engl J Med. 2020;382(7):622-631. doi:10.1056/NEJMoa1803537
Guillevin L, Pagnoux C, Karras A, et al; French Vasculitis Study Group. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014;371(19):1771-1780. doi:10.1056/NEJMoa1404231
Charles P, Perrodeau É, Samson M, et al; French Vasculitis Study Group. Long-term rituximab use to maintain remission of antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2020;173(3):179-187. doi:10.7326/M19-3827
Smith RM, Jones RB, Specks U, et al; RITAZAREM Coinvestigators. Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis. Ann Rheum Dis. 2020;79(9):1243-1249. doi:10.1136/annrheumdis-2019-216863

Reviewed by Hasan Avcu, PhD, on 2/24/2023.

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.

ANCA-Associated Vasculitis (AAV)