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02-03-2017 | ANCA-associated vasculitis | Review | Article

Rituximab in ANCA-Associated Vasculitis

Journal: Current Rheumatology Reports

Authors: Romina I. Hassan, Angelo L. Gaffo

Publisher: Springer US

Abstract

Purpose of Review

The purpose of this review is to describe the efficacy and safety of rituximab (RTX) as a remission induction and maintenance therapy in ANCA-associated vasculitis (AAV).

Recent Findings

A PubMed search was carried out to track down articles published between February 2006 and February 2016. Randomized controlled trials (RCTs) that encompassed patients with AAV were included. The American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) 2014–2015 online abstracts were also reviewed whether they were RTCs or not. Ten PubMed RCTs were analyzed along with eight ACR and four EULAR abstracts. RTX was not inferior to cyclophosphamide (CYC) for remission induction in AAV; it was superior to CYC in patients with relapsing disease and superior for remission maintenance in comparison with azathioprine (AZA).

Summary

Rituximab is a therapeutic option to induce and maintain remission in patients with AAV.
Literature
1.
Walton EW. Giant-cell granuloma of the respiratory tract (Wegener's Granulomatosis). Br Med J. 1958;2(5091):265–270.
2.
Fauci A, Wolff S. Wegener’s granulomatosis: studies in eighteen patients and a review of the literature. Medicine (Baltimore). 1973;52:535–61.CrossRef
3.
Novack ST, Pearson CM. Cyclophosphamide therapy in Wegener’s Granulomatosis. N Engl J Med. 1971;284:938–42.CrossRefPubMed
4.
Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med. 1983;98:76–85.CrossRefPubMed
5.
Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992;116:488–94.CrossRefPubMed
6.
Talar-Williams C, Hijazi YM, Walther MM, Linehan WM, Hallahan CW, Lubensky I, et al. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med. 1996;124:477–84.CrossRefPubMed
7.
Mukhtyar C, Guillevin L, Cid MC, Dasgupta B, Groot K, Hauser T, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009;68(3):310–7. doi:10.​1136/​ard.​2008.​088096.CrossRefPubMed
8.
Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, et al. Pulse vs. daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody–associated vasculitis. Ann Intern Med. 2009;150:670–80.CrossRefPubMed
9.
Harper L, Morgan MD, Walsh M, Hoglund P, Westman K, Flossmann O, 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. doi:10.​1136/​annrheumdis-2011-200477.CrossRefPubMed
10.
Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007;18:2180–8. doi:10.​1681/​ASN.​2007010090.CrossRefPubMed
11.
Walsh M, Merkel PA, Peh CA, Szpirt W, Guillevin L, Pusey CD, et al. Plasma exchange and glucocorticoid dosing in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis (PEXIVAS): protocol for a randomized controlled trial. Trials. 2013;14:73. doi:10.​1186/​1745-6215-14-73.CrossRefPubMedPubMedCentral
12.
de Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, 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. doi:10.​1002/​art.​21142.CrossRefPubMed
13.
Ntatsaki E, Carruthers D, Chakravarty K, D’Cruz D, Harper L, Jayne D, et al. BSR and BHPR guidelines for the management of adults with ANCA associated vasculitis. Rheumatology. 2014;53(12):2306–9. doi:10.​1093/​rheumatology/​ket445.CrossRefPubMed
14.
• Springer J, Nutter B, Langford CA, Hoffman GS, Alexandra VF. Granulomatosis with polyangiitis (Wegener’s) Impact on maintenance therapy duration. Medicine. 2014;93(2):82–90. doi:10.​1097/​MD.​0000000000000020​. This research article shows the importance of both protracted treatment and proper doses to avoid relapses.CrossRefPubMedPubMedCentral
15.
Food and Drug Administration [Internet]. United States: 2011. [Updated October 10, 2014; cited July 4 2016]. Available in: http://​www.​fda.​gov/​NewsEvents/​Newsroom/​PressAnnouncemen​ts/​ucm251946.​htm.
16.
Keogh K, Wylam M, Stone JH, Specks U. Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody–associated vasculitis. Arthritis Rheum. 2005;52(1):262–8. doi:10.​1002/​art.​20718.CrossRefPubMed
17.
Keogh KA, Ytterberg SR, Fervenza FC, Carlson KA, Schroeder DR, Specks U. Rituximab for refractory Wegener’s granulomatosis report of a prospective, open-label pilot trial. Am J Respir Crit Care Med. 2006;173(2):180–7. doi:10.​1164/​rccm.​200507-1144OC.CrossRefPubMed
18.
Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221–32. doi:10.​1056/​NEJMoa0909905.CrossRefPubMedPubMedCentral
19.
•• Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013;369(5):417–27. doi:10.​1056/​NEJMoa1213277. This RTC shows that a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction of remissions in patients with ANCA vasculitis.CrossRefPubMed
20.
Fussner LA, Hummel AM, Schroeder DR, Silva F, Cartin-Ceba R, Snyder MR, et al. Factors determining the clinical utility of serial measurements of antineutrophil cytoplasmic antibodies targeting proteinase 3. Arthritis Rheum. 2016;68(7):1700–10. doi:10.​1002/​art.​39637.CrossRef
21.
Miloslavsky EM, Specks U, Merkel PA, Seo P, Spiera R, Langford CA, et al. Outcomes of nonsevere relapses in antineutrophil cytoplasmic antibody–associated vasculitis treated with glucocorticoids. Arthritis Rheum. 2015;67(6):1629–36. doi:10.​1002/​art.​39104.CrossRef
22.
Miloslavsky EM, Specks U, Merkel PA, Seo P, Spiera R, Langford CA, et al. Rituximab for the treatment of relapses in ANCA-associated vasculitis. Arthritis Rheum. 2014;66(11):3151–9. doi:10.​1002/​art.​38788.CrossRef
23.
Jones RB, ChoenTervaert JW, Hauser H, Lumaqui R, Morgan MD, Peh CA, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010;363(3):211–20. doi:10.​1056/​NEJMoa0909169.CrossRefPubMed
24.
•• Jones RB, Furuta S, Cohen Tervaert JW, Hauser T, Luqmani R, Morgan MD, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial. Ann Rheum Dis. 2015;74(6):1178–82. doi:10.​1136/​annrheumdis-2014-206404. This trial shows that the association of rituximab and cyclophosphamide in severe renal vasculitis is of no benefit in comparison with standard of care after two years of treatment.CrossRefPubMed
25.
Theis D, Langford CA, Hoffman GS, Villa-Forte A. Long-term use of rituximab for eosinophilic granulomatosis with polyangiitis. Arthritis Rheum. 2015;67(Supp 10):1173–4.
26.
Cartin-Ceba R, Fervenza F, Ytterberg SR, Specks U. Diffuse alveolar hemorrhage secondary to ANCA-associated vasculitis: predictors of respiratory failure and clinical outcomes. Arthritis Rheum. 2015;67 Suppl 10:1160.
27.
Specks U. Biologic therapy in ANCA associated vasculitis: new perspectives. Ann Rheum Dis. 2015;74 Suppl 2:3. doi:10.​1136/​annrheumdis-2015-eular.​6807.CrossRef
28.
•• Guillevin L, Pagnoux C, Karras A, Khouatra C, Aumaitre O, Cohen P, et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014;371(19):1771–80. doi:10.​1056/​NEJMoa1404231. This paper proved that RTX is superior to AZA for remission maintenance in AAV in comparison with the standard of care.CrossRefPubMed
29.
Terrier B, Pagnoux C, Geri G, Karras A, Khouatra C, Aumaitre O, et al. Factors predictive of ANCA-associated vasculitis relapse in patients given Rituximab-maintenance therapy. Arthritis Rheum. 2014;66(Suppl10):779.
30.
Draibe J, Pepper RJ, Merkel PA, Salama AD, et al. Serum calprotectin and disease relapse in ANCA-associated vasculitis. Arthritis Rheum. 2014;66(Suppl10):819.
31.
Tan BK, Yoann C, Tasse J, Laurent F, Puechal X, Vinter C, et al. Staphylococcus Aureus nasal carriage and relapses, BVAS, ANCA-positivity and cotrimoxazole use in ANCA associated vasculitis. Arthritis Rheum. 2014;66(Suppl10):779–80.
32.
Besada E, Koldingsnes W, Nossent JC. Chronic nasal carriage of Staphylococcus Aureus does not increase the risk of relapse and severe infections in Granulomatosis with polyangiitis patients when receiving rituximab maintenance treatment. Ann Rheum Dis. 2014;73 Suppl 2:556. doi:10.​1136/​annrheumdis-2014-eular.​5231.
33.
Solans-Laqué R, Rodriguez-Carballeira M, Fraile G, Castillo MJ, Rios J, Saez L, et al. Long-term survival and baseline prognostic factors in a wide series of patients with AAV from Spain. Usefulness of prognostic scores (REVAS study). Ann Rheum Dis. 2015;74 Suppl 2:524. doi:10.​1136/​annrheumdis-2015-eular.​4229.CrossRef
34.
Garcia Vives E, Ramentol M, Segarra A, Martínez-Valle F, Loureiro J, Agraz I, et al. Influence of infections on the prognosis of ANCA associates vasculitis (AAV). Ann Rheum Dis. 2015;74 Suppl 2:1112–3. doi:10.​1136/​annrheumdis-2015-eular.​2051.CrossRef
35.
Fukui S, Iwamoto N, Umeda M, Nishino A, Nakashima Y, Koga T, et al. ANCA associated vasculitis with hypocomplementemia Has more diffuse alveolar hemorrhage and a poor prognosis. Arthritis Rheum. 2015;67 Suppl 10:1161–2.
36.
Goker B, Haznedaroglu S, Kucuk H, Varan O, Bitik B, Tufan A, et al. Neutrophil/lymphocyte ratio: could It be a prognostic indicator for renal outcome in patients with granulomatosis with polyangiitis? Arthritis Rheum. 2015;67 Suppl 10:1138.