Advances in therapy for ANCA-associated vasculitis

Current Rheumatology Reports

Volumn 14, Issue 6, 2012, Pages 509-515

  Geetha, Duvuru ^a   Seo, Philip ^b  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

ANCA; ANCA associated vasculitis; Biological therapy; Cyclophosphamide; Granulomatosis with polyangiitis; Microscopic polyangiitis; Plasma exchange; Remission; Therapy; Treatment; Wegener's granulomatosis

Indexed keywords

AZATHIOPRINE; COTRIMOXAZOLE; CYCLOPHOSPHAMIDE; ETANERCEPT; METHOTREXATE; METHYLPREDNISOLONE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PLACEBO; PREDNISOLONE; RITUXIMAB;

ADJUVANT THERAPY; ANCA ASSOCIATED GLOMERULONEPHRITIS; ANCA ASSOCIATED VASCULITIS; BIOLOGICAL THERAPY; CONTROLLED CLINICAL TRIAL (TOPIC); DRUG DOSE REDUCTION; GLOMERULONEPHRITIS; HUMAN; META ANALYSIS (TOPIC); MICROSCOPIC POLYANGIITIS; PLASMAPHERESIS; PROGNOSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RELAPSE; REMISSION; REVIEW; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; WEGENER GRANULOMATOSIS;

ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED VASCULITIS; ANTIBODIES, MONOCLONAL, MURINE-DERIVED; ANTIRHEUMATIC AGENTS; CYCLOPHOSPHAMIDE; GLUCOCORTICOIDS; HUMANS; METHOTREXATE; PLASMA EXCHANGE; RECURRENCE; REMISSION INDUCTION;

EID: 84869235523     PISSN: 15233774     EISSN: 15346307     Source Type: Journal    
DOI: 10.1007/s11926-012-0284-0     Document Type: Review

References (35)

1. Seo P, Stone JH. The antineutrophil cytoplasmic antibodyassociated vasculitides. Am J Med. 2004; 117(1): 39-50.
2. Chung SA, Seo P. Microscopic polyangiitis. Rheum Dis Clin North Am. 2010; 36(3): 545-58.
3. Gadola SD, Gross WL. Vasculitis in 2011: The renaissance of granulomatous inflammation in AAV. Nat Rev Rheumatol. 2012; 8(2): 74-6.
4. Wolff S, Fauci A, Horn R, Dale D. Wegener's granulomatosis. Ann Intern Med. 1974; 81: 513-25.
5. Wohlwill F. Ueber die nur mikroskopisch erkenbarre form der periarteritis nodosa. Arch Pathol Anat. 1923; 246: 377-411.
6. Fauci A, Doppman J, Wolff S. Cyclophosphamide-induced remissions in advanced polyarteritis nodosa. Am J Med. 1978; 64: 890-4. (Pubitemid 8328141)
7. Fauci A, Wolff S. Wegener's granulomatosis: Studies in eighteen patients and a review of the literature. Medicine. 1973; 52: 53-61.
8. Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener's granulomatosis: An analysis of 158 patients. Ann Intern Med. 1992; 116: 488-98.
9. Langford C, Talar-Williams C, Barron K, Sneller M. A staged approach to the treatment of Wegener's granulomatosis: Induction of remission with glucocorticoids and daily cyclophosphamide switching to methotrexate for remission maintenance. Arthritis Rheum. 1999; 42(12): 2666-73. (Pubitemid 30327189)
10. Jayne D. Randomised trial of cyclophosphamide versus azathioprine during remission in ANCA-associated systemic vasculitis (CYCAZAREM). J Am Soc Nephrol. 1999; 10: 105A.
11. Pagnoux C, Mahr A, Hamidou MA, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008; 359(26): 2790-803.
12. Hiemstra TF, Walsh M, Mahr A, et al. Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: A randomized controlled trial. JAMA. 2010; 304(21): 2381-8.
13. Zahr N, Arnaud L, Marquet P, et al. Mycophenolic acid area under the curve correlates with disease activity in lupus patients treated with mycophenolate mofetil. Arthritis Rheum. 2010; 62(7): 2047-54.
14. Guillevin L, Cordier J, Lhote F, et al. A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener's granulomatosis. Arthritis Rheum. 1997; 40 (12): 2187-98. (Pubitemid 28016415)
15. de Groot K, Adu D, Savage CO. The value of pulse cyclophosphamide in ANCA-associated vasculitis: Meta-analysis and critical review. Nephrol Dial Transplant. 2001; 16(10): 2018-27. (Pubitemid 32970564)
16. De Groot K, Rasmussen N, Bacon PA, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005; 52(8): 2461-9. (Pubitemid 41117433)
17. Harper L, Morgan MD, Walsh M, et al. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: Long-term follow-up. Ann Rheum Dis. 2012; 71(6): 955-60.
18. de Groot K, Muhler M, Reinhold-Keller E, Paulsen J, Gross W. Induction of remission in Wegener's granulomatosis with low dose methotrexate. J Rheumatol. 1998; 25: 492-5. (Pubitemid 28109351)
19. Hoffman GS, Langford CA. Can methotrexate replace cyclophosphamide in the treatment of a subset of Wegener's granulomatosis and microscopic polyangiitis? Nat Clin Pract Rheumatol. 2006; 2 (2): 70-1. (Pubitemid 43239204)
20. Langford C, Fauci A, Talar-Williams C, Sneller M. Treatment of Wegener's granulomatosis with methotrexate and glucocorticoids: Update on rate of relapse. Arthritis Rheum. 1996; 39: S211.
21. Faurschou M, Westman K, Rasmussen N, et al. Long-term outcome of a clinical trial comparing methotrexate to cyclophosphamide for remission induction of early systemic ANCAassociated vasculitis. Arthritis Rheum. 2012. It is sobering to realize that a strategy that initially seemed to spare patients from exposure to cyclophosphamide may not work as well as we had hoped. Presumably, in cases where equipoise seems to exist, cyclophosphamide should be chosen over methotrexate as an initial remission induction strategy until the implications of this study are clearer.
22. Villa-Forte A, Clark TM, Gomes M, et al. Substitution of methotrexate for cyclophosphamide in Wegener granulomatosis: A 12- year single-practice experience. Medicine (Baltimore). 2007; 86 (5): 269-77. (Pubitemid 47415005)
23. Pinching A, Rees A, Pussell B, Lockwood C, Mitchison R, Peters D. Relapses in Wegener's granulomatosis: The role of infection. BMJ. 1980; 281: 836-8. (Pubitemid 10059945)
24. Jennette JC, Falk RJ, Gasim AH. Pathogenesis of antineutrophil cytoplasmic autoantibody vasculitis. Curr Opin Nephrol Hypertens. 2011; 20(3): 263-70.
25. Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009; 68(3): 310-7.
26. Jayne DR, Gaskin G, Rasmussen N, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007; 18 (7): 2180-8. (Pubitemid 47041083)
27. Walsh M, Catapano F, Szpirt W, et al. Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: A meta-analysis. Am J Kidney Dis. 2011; 57(4): 566-574. This metaanalysis is the closest we have to a definitive statement regarding the utility of plasma exchange for patients with ANCA-associated glomerulonephritis.
28. Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med. 2005; 352(4): 351-61.
29. de Menthon M, Cohen P, Pagnoux C, et al. Infliximab or rituximab for refractory Wegener's granulomatosis: Long-term follow up A prospective randomised multicentre study on 17 patients. Clin Exp Rheumatol. 2011; 29(1 Suppl 64): S63-71.
30. Booth A, Harper L, Hammad T, et al. Prospective study of TNFalpha blockade with infliximab in anti-neutrophil cytoplasmic antibodyassociated systemic vasculitis. J Am Soc Nephrol. 2004; 15(3): 717-21. (Pubitemid 38294802)
31. Zouboulis C, et al. Adamantiades-behcet's disease: Interleukin-8 is increased in serum of patients with active oral and neurological manifestations and is secreted by small vessel endothelial cells. Arch Dermatol Res. 2000; 292: 279-84. (Pubitemid 30386437)
32. 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. This article, and the subsequent reference, let to the first drug approved by the United States Food and Drug Administration for the treatment of systemic vasculitis. Reviewing both articles carefully will give you a better sense of the limits of our understanding regarding the use of rituximab for patients with ANCA-associated vasculitis.
33. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010; 363 (3): 221-32.
34. Holle JU, Dubrau C, Herlyn K, et al. Rituximab for refractory granulomatosis with polyangiitis (Wegener's granulomatosis): Comparison of efficacy in granulomatous versus vasculitic manifestations. Ann Rheum Dis. 2012; 71(3): 327-33.
35. Smith RM, Jones RB, Guerry MJ, et al. Rituximab for remission maintenance in relapsing ANCA-associated vasculitis. Arthritis Rheum. 2012. Epub ahead of print. The key unanswered question regarding rituximab is how to use the drug for remission maintenance. This study describes the outcomes associated with one possible re-treatment strategy.