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Dtsch Med Wochenschr 2020; 145(01): 40-46
DOI: 10.1055/a-1060-2736
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Anti-B-Zell-Antikörpertherapie zur Remissionserhaltung bei Granulomatose mit Polyangiitis und mikroskopischer Polyangiitis

Anti B-cell-antibody treatment for maintenance of remission in granulomatosis with polyangiitis and microscopic polyangiitis
Kirsten de Groot
1   Medizinische Klinik III (Nephrologie, Dialyse, Hypertensiologie, Rheumatologie), Klinikum Offenbach GmbH und KfH-Nierenzentrum Offenbach/Main
,
Peer Malte Aries
2   Rheumatologie im Struenseehaus, Hamburg
,
Marion Haubitz
3   Medizinische Klinik III (Nieren- und Hochdruckerkrankungen), Klinikum Fulda
,
Bernhard Hellmich
4   Klinik für Innere Medizin, Rheumatologie und Immunologie, Vaskulitiszentrum-Süd, Medius-Kliniken, Akademisches Lehrkrankenhaus der Universität Tübingen, Kirchheim-Teck
,
Peter Lamprecht
5   Klinik für Rheumatologie und klinische Immunologie, Universität zu Lübeck, Lübeck
,
Jens Thiel
6   Klinik für Rheumatologie und Klinische Immunologie, Department Innere Medizin, Medizinische Fakultät, Universitätsklinikum Freiburg, Freiburg
› Author Affiliations
Further Information

Publication History

Publication Date:
08 January 2020 (online)

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Zusammenfassung

Die Granulomatose mit Polyangiitis (GPA) und die mikroskopische Polyangiitis (MPA) stellen als primäre nekrotisierende Kleingefäßvaskulitiden die häufigsten ANCA-assoziierten Vaskulitiden dar. Bei diesen, früher oft tödlich verlaufenden Erkrankungen kann heute durch eine Stadien-adaptierte Immunsuppression in den meisten Fällen eine Remission erzielt werden. Diese mündet jedoch nicht in eine Heilung oder medikamentenfreie Langzeitremission. Es bedarf deshalb einer remissionserhaltenden Therapie. Aktuelle randomisierte kontrollierte Studien zeigen, dass unter einer remissionserhaltenden Behandlung mit halbjährlich verabreichtem anti-B-Zell-Antikörper Rituximab weniger Rezidive auftreten als unter der bisherigen Standardmedikation mit Azathioprin bei vergleichbarem Nebenwirkungsprofil. Diese Daten führten 2018 zur Zulassung von Rituximab als remissionserhaltende Therapie der GPA und MPA. Unter einer solchen Rituximab-Therapie muss mit einer Immunglobulindepletion sowie späten Zytopenien mit begleitenden Infekten gerechnet werden. Leitlinien und Expertenempfehlungen zu Infektprophylaxen, Impfungen und Immunglobulinsubstitution werden in diesem Beitrag vorgestellt.

Abstract

Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are the most frequent primary necrotizing small vessel vasculitides. In these formerly fatal diseases remission can be induced by stage- and activity-adapted immunosuppressive regimens in the majority of patients. This does not lead to drug-free long-term remission or even cure. Consequently, maintenance of remission medication is needed. Recent randomized controlled trials demonstrated that maintenance treatment with the anti-B-cell antibody Rituximab, administered 6-monthly as opposed to azathioprine leads to a significantly lower relapse rate but a similar profile of adverse events. These data enabled the extension of the approval of Rituximab for maintenance of remission treatment of GPA and MPA in Germany in 2018. Guidelines and expert recommendations concerning measures of infection prevention and vaccination of immunosuppressed patients as well as the management of hypogammaglobulinemia and cytopenia on Rituximab are presented in this review.

Schlüsselwörter

Granulomatose mit Polyangiitis - mikroskopische Polyangiitis - Remissionserhaltung - B-Zell-gerichtete Therapie - Rituximab

Key Words

granulomatosis with polyangiitis - microscopic polyangiitis - maintenance of remission - B-cell-targeted therapy - Rituximab
 

  • Literatur

  • 1 Jennette JC, Falk RJ, Bacon PA. et al. 2012 revised international chapel hill consensus conference nomenclature of vasculitides. Arthritis Rheum 2013; 65: 1-11
    CrossrefPubMedSearch in Google Scholar
  • 2 Holle JU, Gross WL, Latza U. et al. Improved outcome in 445 patients with Wegener’s granulomatosis in a German vasculitis center over four decades. Arthritis Rheum 2011; 63: 257-266
    CrossrefPubMedSearch in Google Scholar
  • 3 Heijl C, Mohammad AJ, Westman K. et al. Long-term patient survival in a Swedish population-based cohort of patients with ANCA-associated vasculitis. RMD Open 2017; 3: e000435
    CrossrefPubMedSearch in Google Scholar
  • 4 Robson J, Doll H, Suppiah R. et al. Damage in the anca-associated vasculitides: long-term data from the European vasculitis study group (EUVAS) therapeutic trials. Ann Rheum Dis 2013; 74: 177-184
    PubMedSearch in Google Scholar
  • 5 Flossmann O, Berden A, de Groot K. et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis 2011; 70: 488-494
    CrossrefPubMedSearch in Google Scholar
  • 6 Jones RB, Tervaert JW, Hauser T. et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 2010; 363: 211-220
    CrossrefPubMedSearch in Google Scholar
  • 7 Stone JH, Merkel PA, Spiera R. et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010; 363: 221-232
    CrossrefPubMedSearch in Google Scholar
  • 8 Unizony S, Villarreal M, Miloslavsky EM. et al. Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Ann Rheum Dis 2016; 75: 1166-1169
    CrossrefPubMedSearch in Google Scholar
  • 9 Schonermarck U, Gross WL, de Groot K. Treatment of ANCA-associated vasculitis. Nat Rev Nephrol 2014; 10: 25-36
    CrossrefPubMedSearch in Google Scholar
  • 10 Schirmer JH, Aries PM, de Groot K. et al. S1 guidelines Diagnostics and treatment of ANCA-associated vasculitis. Z Rheumatol 2017; 76 (03) 77-104
    CrossrefPubMedSearch in Google Scholar
  • 11 Yates M, Watts RA, Bajema IM. et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis 2016; 75: 1583-1594
    PubMedSearch in Google Scholar
  • 12 Moosig F, Aries PM, de Groot K. et al. B-cell targeted therapy in patients with granulomatosis with polyangiitis and microscopic polyangiitis. Dtsch Med Wochenschr 2014; 139: 2248-2253
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 Salmela A, Tornroth T, Poussa T. et al. Prognostic Factors for Survival and Relapse in ANCA-Associated Vasculitis with Renal Involvement: A Clinical Long-Term Follow-Up Study. Int J Nephrol 2018; 2018: 6369814
    PubMedSearch in Google Scholar
  • 14 Specks U, Merkel P, Seo P. et al. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med 2013; 369: 417-427
    CrossrefPubMedSearch in Google Scholar
  • 15 Guillevin L, Pagnoux C, Karras A. et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med 2014; 371: 1771-1780
    CrossrefPubMedSearch in Google Scholar
  • 16 Terrier B, Pagnoux C, Perrodeau E. et al. Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides. Ann Rheum Dis 2018; 77: 1150-1156
    CrossrefPubMedSearch in Google Scholar
  • 17 Charles P, Terrier B, Perrodeau E. et al. 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 2018; 77: 1143-1149
    CrossrefPubMedSearch in Google Scholar
  • 18 Charles P, Dechartres A, Terrier B. et al. Reducing the Number of Rituximab Infusions at Onset of Maintenance Therapy for ANCA-associated Vasculitides: Results of a Post Hoc Analysis from a Randomized–controlled Trial [abstract]. Arthritis Rheumatol 2019 71 (Suppl. 10). Im Internet: https://acrabstracts.org/abstract/reducing-the-number-of-rituximab-infusions-at-onset-of-maintenance-therapy-for-anca-associated-vasculitides-results-of-a-post-hoc-analysis-from-a-randomized-controlled-trial/ ; Stand: 20.11.2019
    PubMedSearch in Google Scholar
  • 19 Gopaluni S, Smith RM, Lewin M. et al. Rituximab versus azathioprine as therapy for maintenance of remission for anti-neutrophil cytoplasm antibody-associated vasculitis (RITAZAREM): study protocol for a randomized controlled trial. Trials 2017; 18: 112
    CrossrefPubMedSearch in Google Scholar
  • 20 Jayne D, Blockmans D, Luqmani R. et al. Efficacy and Safety of Belimumab and Azathioprine for Maintenance of Remission in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Randomized Controlled Study. Arthritis Rheumatol 2019; 71: 952-963
    PubMedSearch in Google Scholar
  • 21 Alberici F, Smith RM, Jones RB. et al. Long-term follow-up of patients who received repeat-dose rituximab as maintenance therapy for ANCA-associated vasculitis. Rheumatology (Oxford) 2015; 54: 1153-1160
    CrossrefPubMedSearch in Google Scholar
  • 22 Torres HA, Hosry J, Mahale P. et al. Hepatitis C virus reactivation in patients receiving cancer treatment: A prospective observational study. Hepatology 2018; 67: 36-47
    CrossrefPubMedSearch in Google Scholar
  • 23 Lin KM, Lin JC, Tseng WY. et al. Rituximab-induced hepatitis C virus reactivation in rheumatoid arthritis. J Microbiol Immunol Infect 2013; 46: 65-67
    CrossrefPubMedSearch in Google Scholar
  • 24 Huang KH, Bonsall D, Katzourakis A. et al. B-cell depletion reveals a role for antibodies in the control of chronic HIV-1 infection. Nat Commun 2010; 1: 102
    CrossrefPubMedSearch in Google Scholar
  • 25 Thiel J, Rizzi M, Engesser M. et al. B cell repopulation kinetics after rituximab treatment in ANCA-associated vasculitides compared to rheumatoid arthritis, and connective tissue diseases: a longitudinal observational study on 120 patients. Arthritis Res Ther 2017; 19: 101
    CrossrefPubMedSearch in Google Scholar
  • 26 Kronbichler A, Kerschbaum J, Gopaluni S. et al. Trimethoprim-sulfamethoxazole prophylaxis prevents severe/life-threatening infections following rituximab in antineutrophil cytoplasm antibody-associated vasculitis. Ann Rheum Dis 2018; 77: 1440-1447
    CrossrefPubMedSearch in Google Scholar
  • 27 Kitazawa T, Seo K, Yoshino Y. et al. Efficacies of atovaquone, pentamidine, and trimethoprim/sulfamethoxazole for the prevention of Pneumocystis jirovecii pneumonia in patients with connective tissue diseases. J Infect Chemother 2019; 25: 351-354
    CrossrefPubMedSearch in Google Scholar
  • 28 Furer V, Rondaan C, Heijstek MW. et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 2019;
    CrossrefPubMedSearch in Google Scholar
  • 29 Wagner N, Assmus F, Arendt G. et al. Impfen bei Immundefizienz. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2019; 62: 494-515
    CrossrefPubMedSearch in Google Scholar
  • 30 Robert-Koch-Institut. Faktenblatt zur Herpes-zoster-Impfung (19.09.2019). Im Internet: https://www.rki.de/DE/Content/Infekt/Impfen/Materialien/Faktenblaetter/Zoster.pdf?__blob=publicationFile ; Stand: 20.11.2019
    PubMed
  • 31 Parrino J, McNeil SA, Lawrence SJ. et al. Safety and immunogenicity of inactivated varicella-zoster virus vaccine in adults with hematologic malignancies receiving treatment with anti-CD20 monoclonal antibodies. Vaccine 2017; 35: 1764-1769
    CrossrefPubMedSearch in Google Scholar
  • 32 Shimizu T, Morita T, Kumanogoh A. The therapeutic efficacy of intravenous immunoglobulin in anti-neutrophilic cytoplasmic antibody-associated vasculitis: a meta-analysis. Rheumatology (Oxford) 2019;
    CrossrefPubMedSearch in Google Scholar
  • 33 Knight A, Sundstrom Y, Borjesson O. et al. Late-onset neutropenia after rituximab in ANCA-associated vasculitis. Scand J Rheumatol 2016; 45: 404-407
    CrossrefPubMedSearch in Google Scholar
  • 34 de Groot K. ANCA-associated vasculitides, an update 2017. Dtsch Med Wochenschr 2017; 142: 1133-1138
    Thieme ConnectPubMedSearch in Google Scholar