Organ- or life-threatening disease

AAV can result in damage to vital organs such as the lungs, kidneys, nervous system, gastrointestinal system, skin, eyes and heart⁴

The majority of AAV patients have evidence of organ- or life-threatening disease¹

Remission induction

For remission induction of non-organ-threatening AAV,
EULAR/ERA–EDTA recommends glucocorticoids PLUS:^2,3

1. Methotrexate (20–25 mg/week, oral or parenteral)

OR

1. Mycophenolate mofetil (maximum 3 g/day)

Remission induction

For remission induction of new-onset organ-threatening or life-threatening AAV, EULAR/ERA–EDTA recommends glucocorticoids (1 mg/kg/day, maximum 80 mg/day) PLUS:³

1. Cyclophosphamide (2 mg/kg/day, maximum 200 mg/day)

OR

1. Rituximab (375 mg/m²/week for 4 weeks)

Remission

1. Full remission is defined as the absence of disease activity attributable to active disease⁵

2. Qualified by the need for ongoing immunosuppressive therapy, in particular glucocorticoids⁵

The response rate is still variable, and many patients do not get into and stay in full remission^6–8

1. Using standard of care treatment, full remission induction, BVAS/WG of 0 along with no ongoing glucocorticoids, can only be achieved in up to 64% of patients with organ- or life-threatening GPA or MPA at 6 months⁶*

2. Up to 48% and 39% of these patients are still in full remission without glucocorticoids at 1 year and 18 months, respectively^7*†

3. Real-world data from EU patients with GPA or MPA highlight the variable response rate to remission induction therapy with a full response observed in only 18%, 43%, 61% and 59% of patients at 1, 3, 6 and 12 months, respectively^8‡

Remission maintenance

For remission maintenance of AAV,
EULAR/ERA–EDTA recommends low-dose glucocorticoids PLUS:³

1. Azathioprine (2 mg/kg/day)

OR

1. Rituximab

OR

1. Methotrexate

OR

1. Mycophenolate mofetil

Relapse

Relapse refers to any disease previously well-controlled with or without treatment that has become active again²

1. Minor relapse: increase in ≥1 new or worse minor items and no major BVAS items²

2. Major relapse: increase in ≥1 major BVAS item²

Relapse in AAV remains common, with approximately 5–10% of patients experiencing relapses of varying severity each year despite continued immunosuppression.^{3,8–11‡§}

For a major relapse of organ-threatening or life-threatening AAV, EULAR/ERA–EDTA recommends treatment as per new disease with glucocorticoids PLUS:³

1. Cyclophosphamide

OR

1. Rituximab

Refractory

Refractory disease is defined as:³

1. Unchanged or increased disease activity in acute AAV after 4 weeks of treatment with standard therapy in acute AAV

OR

1. Lack of response (<50% reduction in disease activity score, e.g. BVAS or BVAS/WG after 6 weeks of treatment)

OR

1. Chronic, persistent disease (presence of ≥1 major or ≥3 minor items on the disease activity score after >12 weeks of treatment)

For AAV refractory to remission induction therapy,
EULAR/ERA–EDTA recommends switching from:³

1. Cyclophosphamide to rituximab

OR

1. Rituximab to cyclophosphamide

Patients should be managed in close conjunction with, or referred to, an expert centre for further evaluation and potential enrolment in clinical trials³

References & footnotes

AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic autoantibody; BVAS, Birmingham Vasculitis Activity Score; ERA–EDTA, European Renal Association—European Dialysis and Transplant Association; EU, European Union; EULAR, European League Against Rheumatism; EUVAS, European Vasculitis Study Group; GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis; MPO, myeloperoxidase; PR3, proteinase 3; RCT, randomised controlled trial; WG, Wegener’s Granulomatosis

*The following treatments are not currently indicated to treat AAV; however, in order to provide a fair representation of the clinical landscape of AAV treatments, all recommended AAV treatments as per the EULAR guidelines have been outlined. VIFOR does not endorse the use of medicinal products outside of their marketing licence.

† Multicentre, randomised, double-blind, double-dummy, noninferiority trial of rituximab (375 mg/m2/week for 4 weeks; n=99; mean age at symptom onset: 54.0 years; male: 46%; GPA: 75%; MPA: 24%; indeterminate: 1%) vs. cyclophosphamide (2 mg/kg/day; n=98; mean age at symptom onset: 51.5 years; male: 54%; GPA: 76%; MPA: 24%) for remission induction in patients with severe AAV (PR3-/MPO-ANCA positive). Glucocorticoids were tapered off; the primary endpoint was remission of disease (BVAS/WG of 0) without the use of prednisone at 6 months. Patients were enrolled between 30 December 2004 and 30 June 2008;¹³ ‡ Patients in the rituximab group who completed glucocorticoid tapering and had sustained disease remission (BVAS/WG of 0) received no further active treatment. In the cyclophosphamide group, patients achieving remission between month 3 and month 6 discontinued treatment and initiated azathioprine (2 mg/kg) for the balance of the 18 months;¹⁴ § Retrospective study reviewing 929 incident AAV patients (GPA: 54%; MPA: 46%; mean age: 56.8 years; male: 53.7%) from four EU countries (399 physicians) who initiated remission induction therapy between November 2014 and February 2017 with data collected at baseline presentation, and after 1, 3, 6 and 12 months of treatment (59% cyclophosphamide, 24% rituximab, 83% glucocorticoids);¹⁵ ¶ Patients (n=535; median age: 61 years) with newly diagnosed GPA (53%) or MPA (47%; adapted Chapel Hill disease definitions) recruited into four EUVAS RCTs in hospitals in 15 countries between 1995 and 2002.¹⁷

1. Little MA, et al. Ann Rheum Dis 2010;69(6):1036−43.

2. Yates M, Watts R. Clin Med (Lond) 2017;17(1):60–4.

3. Ntatsaki E, et al. Rheumatology (Oxford) 2014;53(12):2306–9.

4. Yates M, et al. Ann Rheum Dis 2016;75(9):1583–94.

5. Roche (2020). Mabthera (rituximab). Summary of Product Characteristics.

6. ADVANZ Pharma (2017). Pevanti (prednisolone). Summary of Product Characteristics.

7. Sandoz (2017). Cyclophosphamide (cyclophosphamide monohydrate). Summary of Product Characteristics.

8. Mylan (2019). Azathioprine (azathioprine). Summary of Product Characteristics.

9. Pfizer (2019). Matrex (methotrexate). Summary of Product Characteristics.

10. Roche (2020). CellCept (mycophenolate mofetil). Summary of Product Characteristics.

11. Al-Hussain T, et al. Adv Anat Pathol 2017;24(4):226–34.

12. Hellmich B, et al. Ann Rheum Dis 2007;66(5):605–17.

13. Stone JH, et al. N Engl J Med 2010;363(3):221–32.

14. Specks U, et al. N Engl J Med 2013;369(5):417–27.

15. Rutherford P, et al. Arthritis Rheumatol 2018(Suppl 10[Abstract 2724]).

16. Rutherford PA, et al. J Am Soc Nephrol 2018;29:839(Abstract SA-PO402).

17. Walsh M, et al. Arthritis Rheum 2012;64(2):542–8.

18. Smith RM, et al. Arthritis Res Ther 2012;14(2):210.

References & footnotes

AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic antibody; BVAS, Birmingham Vasculitis Activity Score; ENT, ear, nose and throat; ERA-EDTA, European Renal Association-European Dialysis and Transplant Association; EU, European Union; EULAR, European League Against Rheumatism; GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis

*Disease severity was defined as mild (localised disease with no systemic symptoms), moderate (systemic disease with lung and/or kidney involvement) or severe (rapidly progressive systemic disease with lung and/or kidney involvement);^{5 †}Retrospective study reviewing 929 incident AAV patients (GPA: 54%; MPA: 46%; mean age: 57 years; male: 54%) and 268 relapsing AAV patients (GPA: 54%; MPA:46%; mean age: 58 years; male: 60%), from four EU countries (399 physicians) who initiated remission induction therapy between November 2014 and February 2017 with data collected at baseline presentation, and after 1, 3, 6 and 12 months of treatment;^{5,8,9 ‡}Retrospective study of AAV patients presenting to the rheumatology (n=15; mean age: 52 years; male: 33%) or nephrology (n=30; mean age: 65; male: 53%) department at Galway University Hospitals from June 2002 and July 2011.⁶

1. Yates M, et al. Ann Rheum Dis 2016;75(9):1583–94.

2. Robson JC, et al. Rheumatol Int 2018;38(4):675–82.

3. Yates M, Watts R. Clin Med (Lond) 2017;17(1):60–4.

4. Robson J, et al. Rheumatology 2015;54(3):471–81.

5. Rutherford P, Götte D. Ann Rheum Dis 2019;78:436–7.

6. McNicholas BA, et al. QJM 2016;109(12):803–9.

7. Harmour S, et al. Ther Clin Risk Manag 2010;6:253–64.

8. Rutherford PA, et al. J Am Soc Nephrol 2018;29:839(Abstract SA-PO403).

9. Rutherford PA, et al. J Am Soc Nephrol 2018;29:839(Abstract SA-PO402).

References & footnotes

AAV, ANCA-associated vasculitis; AE, adverse event; ANCA, anti-neutrophil cytoplasmic antibody; EU, European Union; GC, glucocorticoid; GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis;

*Retrospective study reviewing 929 incident AAV patients (GPA: 54%; MPA: 46%; mean age: 57 years; male: 54%) and 268 relapsing AAV patients (GPA: 54%; MPA:46%; mean age: 58 years; male: 60%) from four EU countries (399 physicians) who initiated remission induction therapy between November 2014 and February 2017 with data collected at baseline presentation, and after 1, 3, 6 and 12 months of treatment.⁸

1. Rutherford P, et al. Nephrol Dial Transplant 2019;34(Suppl 1).

2. Yates M, et al. Ann Rheum Dis 2016;75(9):1583–94.

References & footnotes

AAV, ANCA-associated vasculitis; ANCA, anti-neutrophil cytoplasmic autoantibody

1. Little MA, et al. Ann Rheum Dis 2010;69(6):1036−43.

2. Salvadori M, Tsalouchos A. World J Nephrol 2018;7(3):71–83.

3. Jennette JC, Nachman PH. Clin J Am Soc Nephrol 2017;12(10):1680–91.