Advertisement

Low-dose rituximab as induction therapy for ANCA-associated vasculitis

  • Yukiko Takakuwa
  • Hironari HanaokaEmail author
  • Tomofumi Kiyokawa
  • Harunobu Iida
  • Hisae Fujimoto
  • Yoshioki Yamasaki
  • Hidehiro Yamada
  • Kimito Kawahata
Brief Report
  • 103 Downloads

Abstract

Administration of four once-weekly doses of 375 mg/m2 rituximab (RTX) is commonly used as remission induction therapy for ANCA-associated vasculitis (AAV). Low-dose RTX has been recently shown to produce closely similar results to conventional treatments in other autoimmune diseases. However, the therapeutic potential of this approach in AAV remains largely unknown. Here, we analyzed the efficacy and tolerability of high- and low-dose regimens of RTX in patients with AAV. We retrospectively examined AAV patients who met the classification algorithm of Watts et al. from 2006 to 2016. Patients were divided into high- (HD) and low-dose (LD) RTX groups. HD-RTX was the original regimen while LD-RTX consisted of two once-weekly doses of 375 mg/m2. Cumulative complete remission (CR) rates for 1 year were compared, and serial changes in peripheral B cell counts and serious adverse events were monitored. Apart from a higher percentage of elderly patients in the LD group (p < 0.01), the 17 patients with HD-RTX and 11 patients with LD-RTX showed no significant differences in clinical characteristics, including Birmingham Vasculitis Activity Score (BVAS), Vasculitis Damage Index (VDI), and the initial dose of glucocorticoid. On 1-year observation, cumulative CR rates did not significantly differ (p = 0.20). Further, peripheral B cell counts and incidence of serious adverse events also did not differ. Cumulative CR rate did not significantly differ between LD and HD groups. Further study is warranted to confirm these results.

Keywords

ANCA-associated vasculitis High dose Low dose Rituximab 

Notes

Compliance with ethical standards

Disclosures

None.

References

  1. 1.
    Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS (1992) Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 116(6):488–498.  https://doi.org/10.7326/0003-4819-116-6-488 CrossRefGoogle Scholar
  2. 2.
    Flossmann O, Berden A, de Groot K, Hagen C, Harper L, Heijl C, Hoglund P, Jayne D, Luqmani R, Mahr A, Mukhtyar C, Pusey C, Rasmussen N, Stegeman C, Walsh M, Westman K, European Vasculitis Study Group (2011) Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis 70(3):488–494.  https://doi.org/10.1136/ard.2010.137778 CrossRefGoogle Scholar
  3. 3.
    Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T, Hellmich B, Holle JU, Laudien M, Little MA, Luqmani RA, Mahr A, Merkel PA, Mills J, Mooney J, Segelmark M, Tesar V, Westman K, Vaglio A, Yalcindag N, Jayne DR, Mukhtyar C (2016) EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 75(9):1583–1594.  https://doi.org/10.1136/annrheumdis-2016-209133 CrossRefGoogle Scholar
  4. 4.
    Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U, RAVE-ITN Research Group (2010) Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 363(3):221–232.  https://doi.org/10.1056/NEJMoa0909905 CrossRefGoogle Scholar
  5. 5.
    Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR, European Vasculitis Study Group (2010) Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 363(3):211–220.  https://doi.org/10.1056/NEJMoa0909169 CrossRefGoogle Scholar
  6. 6.
    Specks U, Fervenza FC, McDonald TJ, Hogan MC (2001) Response of Wegener's granulomatosis to anti-CD20 chimeric monoclonal antibody therapy. Arthritis Rheum 44(12):2836–2840CrossRefGoogle Scholar
  7. 7.
    Cartin-Ceba R, Golbin JM, Keogh KA, Peikert T, Sanchez-Menendez M, Ytterberg SR, Fervenza FC (2012) Specks U (2012) rituximab for remission induction and maintenance in refractory granulomatosis with polyangiitis (Wegener's): ten-year experience at a single center. Arthritis Rheum 64(11):3770–3778.  https://doi.org/10.1002/art.34584 CrossRefGoogle Scholar
  8. 8.
    Chatzidionysiou K, Lie E, Nasonov E, Lukina G, Hetland ML, Tarp U, Ancuta I, Pavelka K, Nordstrom DC, Gabay C, Canhao H, Tomsic M, van Riel PL, Gomez-Reino J, Kvien TK, van Vollenhoven RF, Rheumatic Diseases Portuguese Register (2016) Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort: data from the CERERRA collaboration. Arthritis Res Ther 18:50.  https://doi.org/10.1186/s13075-016-0951-z CrossRefGoogle Scholar
  9. 9.
    Zaja F, Vianelli N, Volpetti S, Battista ML, Defina M, Palmieri S, Bocchia M, Medeot M, De Luca S, Ferrara F, Isola M, Baccarani M, Fanin R (2010) Low-dose rituximab in adult patients with primary immune thrombocytopenia. Eur J Haematol 85(4):329–334.  https://doi.org/10.1111/j.1600-0609.2010.01486.x CrossRefGoogle Scholar
  10. 10.
    Vieira CA, Agarwal A, Book BK, Sidner RA, Bearden CM, Gebel HM, Roggero AL, Fineberg NS, Taber T, Kraus MA, Pescovitz MD (2004) Rituximab for reduction of anti-HLA antibodies in patients awaiting renal transplantation: 1. Safety, pharmacodynamics, and pharmacokinetics. Transplantation 77(4):542–548CrossRefGoogle Scholar
  11. 11.
    Watts R, Lane S, Hanslik T, Hauser T, Hellmich B, Koldingsnes W, Mahr A, Segelmark M, Cohen-Tervaert JW, Scott D (2007) Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Ann Rheum Dis 66(2):222–227.  https://doi.org/10.1136/ard.2006.054593 CrossRefGoogle Scholar
  12. 12.
    Mukhtyar C, Lee R, Brown D, Carruthers D, Dasgupta B, Dubey S, Flossmann O, Hall C, Hollywood J, Jayne D, Jones R, Lanyon P, Muir A, Scott D, Young L, Luqmani RA (2009) Modification and validation of the Birmingham Vasculitis Activity Score (version 3). Ann Rheum Dis 68(12):1827–1832.  https://doi.org/10.1136/ard.2008.101279 CrossRefGoogle Scholar
  13. 13.
    Exley AR, Bacon PA, Luqmani RA, Kitas GD, Gordon C, Savage CO, Adu D (1997) Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum 40(2):371–380.  https://doi.org/10.1002/art.1780400222 CrossRefGoogle Scholar
  14. 14.
    National Cancer Institute; Common terminology criteria for adverse events v3.0. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf. Accessed 29 Apr 2010
  15. 15.
    Lamprecht P, Kerstein A, Klapa S, Schinke S, Karsten CM, Yu X, Ehlers M, Epplen JT, Holl-Ulrich K, Wiech T, Kalies K, Lange T, Laudien M, Laskay T, Gemoll T, Schumacher U, Ullrich S, Busch H, Ibrahim S, Fischer N, Hasselbacher K, Pries R, Petersen F, Weppner G, Manz R, Humrich JY, Nieberding R, Riemekasten G, Muller A (2018) Pathogenetic and clinical aspects of anti-neutrophil cytoplasmic autoantibody-associated vasculitides. Front Immunol 9:680.  https://doi.org/10.3389/fimmu.2018.00680 CrossRefGoogle Scholar
  16. 16.
    Jayne D (2001) Update on the European vasculitis study group trials. Curr Opin Rheumatol 13(1):48–55CrossRefGoogle Scholar
  17. 17.
    Charles P, Terrier B, Perrodeau E, Cohen P, Faguer S, Huart A, Hamidou M, Agard C, Bonnotte B, Samson M, Karras A, Jourde-Chiche N, Lifermann F, Gobert P, Hanrotel-Saliou C, Godmer P, Martin-Silva N, Pugnet G, Matignon M, Aumaitre O, Viallard JF, Maurier F, Meaux-Ruault N, Riviere S, Sibilia J, Puechal X, Ravaud P, Mouthon L, Guillevin L, French Vasculitis Study Group (2018) Comparison of individually tailored versus fixed-schedule rituximab regimen to maintain ANCA-associated vasculitis remission: results of a multicentre, randomised controlled, phase III trial (MAINRITSAN2). Ann Rheum Dis 77(8):1143–1149.  https://doi.org/10.1136/annrheumdis-2017-212878 Google Scholar
  18. 18.
    Visentini M, Tinelli C, Colantuono S, Monti M, Ludovisi S, Gragnani L, Mitrevski M, Ranieri J, Fognani E, Piluso A, Granata M, De Silvestri A, Scotti V, Mondelli MU, Zignego AL, Fiorilli M, Casato M (2015) Efficacy of low-dose rituximab for the treatment of mixed cryoglobulinemia vasculitis: phase II clinical trial and systematic review. Autoimmun Rev 14(10):889–896.  https://doi.org/10.1016/j.autrev.2015.05.013 CrossRefGoogle Scholar
  19. 19.
    Cornec D, Kabat BF, Mills JR, Cheu M, Hummel AM, Schroeder DR, Cascino MD, Brunetta P, Murray DL, Snyder MR, Fervenza F, Hoffman GS, Kallenberg CGM, Langford CA, Merkel PA, Monach PA, Seo P, Spiera RF, St Clair EW, Stone JH, Barnidge DR, Specks U (2018) Pharmacokinetics of rituximab and clinical outcomes in patients with anti-neutrophil cytoplasmic antibody associated vasculitis. Rheumatology (Oxford) 57(4):639–650.  https://doi.org/10.1093/rheumatology/kex484 CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.Division of Rheumatology and Allergy, Department of Internal MedicineSt. Marianna University School of MedicineKawasakiJapan
  2. 2.Division of Rheumatology, Department of Internal MedicineSeirei Yokohama HospitalYokohamaJapan

Personalised recommendations