Download PDF
Aktuelle Rheumatologie 2007; 32(3): 166-171
DOI: 10.1055/s-2007-963221
Übersichtsarbeit

© Georg Thieme Verlag KG Stuttgart · New York

B-Zell-Depletion mit Rituximab als neuer therapeutischer Ansatz bei Kollagenosen und Vaskulitiden

B Cell Depletion with Rituximab: A New Approach for the Treatment of Connective Tissue Diseases and VasculitidesH. Nüßlein1
  • 1Medizinische Klinik III, Städt. Klinikum Friedrichstadt
Further Information

Publication History

Publication Date:
27 June 2007 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die B-Zell-depletierende Wirkung des Anti-CD20-Antikörpers Rituximab wird seit Ende der 90er-Jahre erfolgreich zur Behandlung bestimmter Non-Hodgkin-Lymphome genutzt und seit einigen Jahren auch bei gegen Standardtherapie resistenter rheumatoider Arthritis. In jüngster Zeit findet Rituximab aber auch zunehmend Eingang in die Therapie von Kollagenosen und Vaskulitiden, also von Autoimmunkrankheiten, in deren Pathogenese die Bedeutung von B-Zellen bisher widersprüchlich diskutiert wurde. Die vorliegende Arbeit gibt einen umfassenden Überblick der bislang publizierten Studienergebnisse und Fallberichte zur Rituximabbehandlung von Patienten mit systemischem Lupus erythematodes, primärem Sjögren-Syndrom, Vaskulitiden, Dermatomyositis, Polymyositis und systemischer Sklerose. Berücksichtigt man, dass diese Patienten zuvor mehrheitlich schwere, therapierefraktäre Verläufe gezeigt hatten, muss man die bisherigen Behandlungsergebnisse mit Rituximab als äußerst vielversprechend bewerten.

Abstract

The anti-CD20 antibody rituximab is a B-cell depleting agent commonly used since the late 1990s to treat selected non-Hodgkin lymphomas and, more recently, rheumatoid arthritis refractory to disease-modifying antirheumatic drugs and anti-TNF-alpha therapy. Furthermore, during the past few years rituximab has been increasingly used for the treatment of connective tissue diseases and vasculitides, i. e., autoimmune diseases with a still elusive pathogenetic link to B cells. This review provides a complete summary of the published studies and case reports of rituximab in the treatment of patients with systemic lupus erythematosus, primary Sjögren’s syndrome, vasculitides including Wegener’s granulomatosis, microscopic polyarteriitis, and Churg-Strauss syndrome, dermatomyositis, polymyositis, and systemic sclerosis. Given that most of these patients had severe, treatment-refractory disease, the good responses to rituximab seen in the majority of patients appear particularly promising.

Schlüsselwörter

B-Zell-Depletion - Kollagenosen - Vaskulitiden

Key words

B cell depletion - connective tissue diseases - vasculitides

Literatur

  • 1 Adams A B, Barillas-Arias L, Angeles S T. et al . Cyclophosphamide and rituximab combination therapy for the treatment of juvenile-onset scleroderma: 6 patient case series.  Arthritis Rheum. 2006;  54 (Suppl 9) 169 (Abstract 290)
    PubMedGoogle Scholar
  • 2 Adler M, Soliotis F, Thakrar S. et al . Use of rituximab in two unusual antibody-mediated autoimmune disorders.  J R Soc Med. 2005;  98 (6) 271-272
    PubMedGoogle Scholar
  • 3 Albert D, Khan S, Stansberry J. et al . A phase I trial of rituximab (anti-CD20) for treatment of systemic lupus erythematosus.  Arthritis Rheum. 2004;  50 (Suppl) S446 (Abstract 1125)
    PubMedGoogle Scholar
  • 4 Aries P M, Hellmich B, Both M. et al . Lack of efficacy of Rituximab in Wegener’s Granulomatosis with refractory granulomatous manifestations.  Ann Rheum Dis. 2006;  65 (7) 853-858
    PubMedGoogle Scholar
  • 5 Armstrong D J, Wright S A, Finch M B. et al . Active systemic lupus erythematosus successfully treated with Rituximab and oral steroid.  Clin Exp Rheumatol. 2004;  22 (6) 787-788
    PubMedGoogle Scholar
  • 6 Arzoo K, Sadeghi S, Liebman H A. Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab).  Ann Rheum Dis. 2002;  61 (10) 922-924
    CrossrefPubMedGoogle Scholar
  • 7 Barillas-Arias L, Adams A B, Angeles S T. et al . Combination of rituximab and cyclophosphamide for the treatment of chilhood onset systemic lupus erythematosus.  Arthritis Rheum. 2006;  54 (Suppl 9) 689 (Abstract 1725)
    PubMedGoogle Scholar
  • 8 Bhatia A, Ell P J, Edwards J C. Anti-CD20 monoclonal antibody (rituximab) as an adjunct in the treatment of giant cell arteritis.  Ann Rheum Dis. 2005;  64 (7) 1099-1100
    CrossrefPubMedGoogle Scholar
  • 9 Brihaye B, Aouba A, Pagnoux C. et al . Adjunction of rituximab (RTX) to corticosteroids (CS) and immunosuppressants (IS) to treat 8 Ppatients with refractory/relapsing Wegener’s granulomatosis (WG).  Arthritis Rheum. 2006;  54 (Suppl 9) 490-491 (Abstract 1167)
    PubMedGoogle Scholar
  • 10 Cambridge G, Leandro M J, Isenberg D A. et al . B cell depletion therapy in systemic lupus erythematosus: Effect on autoantibody and anti- microbial antibody profiles.  Arthritis Rheum. 2004;  50 (Suppl) Abstract 486
    PubMedGoogle Scholar
  • 11 Carrillo S M, Saavedra M A. Rituximab for severe inflammatory myositis.  Ann Rheum Dis. 2006;  65 (Suppl II) 385
    CrossrefPubMedGoogle Scholar
  • 12 Carrillo-Vázquez S M, Reyes-Salinas A, Saavedra-Salinas M A. Rituximab for severe systemic lupus erythematosus.  Ann Rheum Dis. 2005;  64 (Suppl III) 248
    PubMedGoogle Scholar
  • 13 Chehab G, Sander O, Fischer-Betz R. et al . Anti-CD20 Therapie bei systemischen Lupus erythematodes - Neun Fälle.  Z Rheumatol. 2006;  65 (Suppl 1) S69 (Abstract PODO4 - 4)
    PubMedGoogle Scholar
  • 14 Chung L, Funke A A, Chakravarty E F. et al . Successful use of rituximab for cutaneous vasculitis.  Arch Dermatol. 2006;  142 (11) 1407-1410
    CrossrefPubMedGoogle Scholar
  • 15 Cohen S B, Emery P, Greenwald M W. REFLEX Trial Group . Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks.  Arthritis Rheum. 2006;  54 (9) 2793-2806
    CrossrefPubMedGoogle Scholar
  • 16 Cruz M CL, Onel K B, Wagner-Weiner L. et al . Rituximab therapy in pediatric systemic lupus erythematosus: long-term followup.  Arthritis Rheum. 2006;  54 (Suppl 9) F12
    PubMedGoogle Scholar
  • 17 Devauchelle-Pensec V, Morvan J, Pennec Y. et al . Rituximab (anti-CD20) in the treatmentof primary Sjögren’s syndrome (PSS): Results of an open label study (PHRC Brest 2003).  Ann Rheum Dis. 2005;  64 (Suppl III) 309
    CrossrefPubMedGoogle Scholar
  • 18 Dinh H V, Mc Cormack C, Hall S. et al . Rituximab for the treatment of the skin manifestations of dermatomyositis: a report of 3 cases.  J Am Acad Dermatol. 2007;  56 (1) 148-153
    PubMedGoogle Scholar
  • 19 Edwards J C, Cambridge G. Sustained improvement in rheumatoid arthritis following a protocol designed to deplete B lymphocytes.  Rheumatology. 2001;  40 (2) 205-211
    CrossrefPubMedGoogle Scholar
  • 20 Edwards J C, Szczepanski L, Szechinski J. et al . Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.  N Engl J Med. 2004;  350 (25) 2572-2581
    CrossrefPubMedGoogle Scholar
  • 21 Emery P, Fleischmann R, Filipowicz-Sosnowska A. DANCER Study Group . The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial.  Arthritis Rheum. 2006;  54 (5) 1390-1400
    CrossrefPubMedGoogle Scholar
  • 22 Eriksson P. Nine patients with anti-neutrophil cytoplasmic antibody-positive vasculitis successfully treated with rituximab.  J Intern Med. 2005;  257 (6) 540-548
    PubMedGoogle Scholar
  • 23 Fakhouri F, Canaud G, Hummel A. et al . Rituximab in severe lupus nephritis: Report of 8 cases. American Society of Nephrology Renal Week, November 8 - 13, 2005, Philadelphia, USA, PA.  Abstract SA-PO552
    PubMedGoogle Scholar
  • 24 Flores-Suarez L F. Rituximab is useful in refractory Wegener granulomatosis with predominant granulomatous disease.  Arthritis Rheum. 2006;  54 (Suppl 9) 493 (Abstract 1174)
    PubMedGoogle Scholar
  • 25 Gottenberg J E, Guillevin L, Lambotte O. Club Rheumatismes et Inflammation (CRI) . Tolerance and short term efficacy of rituximab in 43 patients with systemic autoimmune diseases.  Ann Rheum Dis. 2005;  64 (6) 913-920
    CrossrefPubMedGoogle Scholar
  • 26 Gunnarsson I, Jonsdottir T, Sundelin B. et al . Electronmicroscopic resorption of immune deposits following rituximab treatment in membranous lupus nephritis: biopsy - rebiopsy data from 4 patients.  Arthritis Rheum. 2006;  54 (Suppl 9) 259 (Abstract 538)
    PubMedGoogle Scholar
  • 27 Henes J, Fritz J, Horger M. et al . Remissionsinduktion mit Rituximab und Erhaltungstherapie mit Leflunomid - ein neues Therapieschema für den Cyclophosphamid refraktären Morbus Wegener?.  Z Rheumatol. 2006;  65 (Suppl 1) S69 (Abstract FV3 - 2)
    PubMedGoogle Scholar
  • 28 Iglesias-Jiménez E, Callejas J, Morillas-Arques P. et al . Antineutrophil cytoplasmic antibody-associated vasculitis (ANCA): Control of clinical course with anti-CD20.  Ann Rheum Dis. 2006;  65 (Suppl II) 372
    CrossrefPubMedGoogle Scholar
  • 29 Jones R B, Burns S, Koukoulaki M. et al . B cell depletion with rituximab treatment for vasculitis. American Society of Nephrology Renal Week, November 8 - 13, 2005, Philadelphia, USA, PA.  Abstract F-PO1009
    PubMedGoogle Scholar
  • 30 Jonsdottir T, Gunnarsson I, Risselada A P. et al . Rituximab plus cyclophosphamide in severe SLE.  Ann Rheum Dis. 2006;  65 (Suppl II) 200
    PubMedGoogle Scholar
  • 31 Kayser M, Unger L, Nüsslein H G. Rituximab als Therapieoption für Patienten mit refraktären systemischen Autoimmunerkrankungen.  Z Rheumatol. 2006;  65 (Suppl 1) S69 (Abstract PODO4 - 7)
    PubMedGoogle Scholar
  • 32 Keogh K A, Wylam M E, Stone J H. et al . Induction of remission by B lymphocyte depletion in eleven patients with refractory antineutrophil cytoplasmic antibody-associated vasculitis.  Arthritis Rheum. 2005;  52 (1) 262-268
    CrossrefPubMedGoogle Scholar
  • 33 Keogh K A, Ytterberg S R, Fervenza F C. et al . Rituximab for refractory Wegener’s granulomatosis: report of a prospective, open-label pilot trial.  Am J Respir Crit Care Med. 2006;  173 (2) 180-187
    PubMedGoogle Scholar
  • 34 Koukoulaki M, Smith K G, Jayne D R. Rituximab in Churg-Strauss syndrome.  Ann Rheum Dis. 2006;  65 (4) 557-559
    CrossrefPubMedGoogle Scholar
  • 35 Lafyatis R, Kissin E, Viger K. et al . Rituximab treatment for patients with diffuse cutaneous systemic sclerosis - a phase I study.  Arthritis Rheum. 2006;  54 (Suppl 9) 523-524 (Abstract 1255)
    PubMedGoogle Scholar
  • 36 Leandro M J, Cambridge G, Edwards J C. et al . B-cell depletion in the treatment of patients with systemic lupus erythematosus: a longitudinal analysis of 24 patients.  Rheumatology. 2005;  44 (12) 1542-1545
    CrossrefPubMedGoogle Scholar
  • 37 Levine T D. Rituximab in the treatment of dermatomyositis: an open-label pilot study.  Arthritis Rheum. 2005;  52 (2) 601-607
    CrossrefPubMedGoogle Scholar
  • 38 Levy D M, Adams B S, Kahn P J. et al . Rituximab in treatment-resistant childhood- onset systemic lupus erythematosus. 69th Annual Scientific Meeting of the American College of Rheumatology, November 12 - 17, 2005, San Diego, USA, CA.  Abstract 1406
    PubMedGoogle Scholar
  • 39 Looney R J, Anolik J H, Campbell D. et al . B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose- escalation trial of rituximab.  Arthritis Rheum. 2004;  50 (8) 2580-2589
    CrossrefPubMedGoogle Scholar
  • 40 Marks S D, Patey S, Brogan P A. et al . B lymphocyte depletion therapy in children with refractory systemic lupus erythematosus.  Arthritis Rheum. 2005;  52 (10) 3168-3174
    CrossrefPubMedGoogle Scholar
  • 41 Neuwelt C M, Young R G, Mc Ghee R A. et al . Role of rituximab in the treatment of severe central nervous system neuropsychiatric systemic lupus erythematosus as monotherapy or in combination therapy.  Ann Rheum Dis. 2005;  64 (Suppl III) 57
    PubMedGoogle Scholar
  • 42 Noss E H, Hausner-Sypek D L, Weinblatt M E. Rituximab as therapy for refractory polymyositis and dermatomyositis.  J Rheumatol. 2006;  33 (5) 1021-1026
    PubMedGoogle Scholar
  • 43 Omdal R, Wildhagen K, Hansen T. et al . Anti-CD20 therapy of treatment-resistant Wegener’s granulomatosis: favourable but temporary response.  Scand J Rheumatol. 2005;  34 (3) 229-232
    CrossrefPubMedGoogle Scholar
  • 44 Pijpe J, Imhoff G W, Spijkervet F K. et al . Rituximab treatment in patients with primary Sjogren’s syndrome: an open-label phase II study.  Arthritis Rheum. 2005;  52 (9) 2740-2750
    CrossrefPubMedGoogle Scholar
  • 45 Radhakrishnan van J, Weiss S, Nachman P. et al . Rituximab (RMB) in glomerular disease (GD). American Society of Nephrology Renal Week, November 8 - 13, 2005, Philadelphia, USA, PA.  Abstract F-PO880
    PubMedGoogle Scholar
  • 46 Ramos-Remus C, Galvan-Villegas F, Melendez-Mercado C. et al . Rituximab in poly-dermatiomyositis (PM-DM) refractory to conventional treatment. Inter-Hospital Register of Rituximab.  Ann Rheum Dis. 2006;  65 (Suppl II) 267
    PubMedGoogle Scholar
  • 47 Ryan J P, Singer N G, Scalzi L V. Treatment of resistant SLE with rituximab administered without cyclophosphamide.  Arthritis Rheum. 2004;  50 (Suppl) S413-S414 (Abstract 1026)
    CrossrefPubMedGoogle Scholar
  • 48 Saadeh C K, Ramos L G, Mc Gee M. et al . Rituxin in extrarenal lupus.  Ann Rheum Dis. 2005;  64 (Suppl III) 236
    PubMedGoogle Scholar
  • 49 Sansonno D, De Re V, Lauletta G. et al . Monoclonal antibody treatment of mixed cryoglobulinemia resistant to interferon alpha with an anti-CD20.  Blood. 2003;  101 (10) 3818-3826
    CrossrefPubMedGoogle Scholar
  • 50 Scheinberg M A, Hammerschlak N, Kutner J M. et al . Rituximab in refractory autoimmune diseases: Brazilian experience with 28 patients. 69th Annual Scientific Meeting of the American College of Rheumatology, November 12 - 17, 2005, San Diego, USA, CA.  Abstract 1107
    PubMedGoogle Scholar
  • 51 Scott S D. Rituximab: a new therapeutic monoclonal antibody for non-Hodgkin’s lymphoma.  Cancer Pract. 1998;  6 (3) 195-197
    CrossrefPubMedGoogle Scholar
  • 52 Seror R, Sordet C, Gottenberg J E. et al . Good tolerance and efficacy of rituximab on systemic features in 12 patients with primary Sjögren’s syndrome. 69th Annual Scientific Meeting of the American College of Rheumatology, November 12 - 17, 2005, San Diego, USA, CA.  Abstract 970
    PubMedGoogle Scholar
  • 53 Sfikakis P P, Boletis J N, Lionaki S. et al . Clinical responses correlate with deactivation of T cells following therapeutic B-cell depletion in patients with lupus nephritis. European Congress of Rheumatology (EULAR), June 9 - 12, 2004, Berlin, Germany.  Ann Rheum Dis. 2004;  63 (Suppl I) Abstract
    PubMedGoogle Scholar
  • 54 Smolen J S, Emery P, Keystone E C. et al . Consensus Statement on the Use of Rituximab in Patients With Rheumatoid Arthritis.  Ann Rheum Dis. 2006;  Epub ahead of print
    PubMedGoogle Scholar
  • 55 Stasi R, Stipa E, Del Poeta G. et al . Long-term observation of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis treated with rituximab.  Rheumatology. 2006;  45 (11) 1432-1436
    CrossrefPubMedGoogle Scholar
  • 56 Strand V, Balbir-Gurman A, Pavelka K. et al . Sustained benefit in rheumatoid arthritis following one course of rituximab: improvements in physical function over 2 years.  Rheumatology. 2006;  45 (12) 1505-1513
    CrossrefPubMedGoogle Scholar
  • 57 Sultan S M, Isenberg D A, Cambridge G. et al . Clinical outcome in 7 patients with idiopathic inflammatory myositis treated with rituximab. 69th Annual Scientific Meeting of the American College of Rheumatology, November 12 - 17, 2005, San Diego, USA, CA.  Abstract 791
    PubMedGoogle Scholar
  • 58 Tanaka Y, Tokunaga M, Nawata M. et al . A pilot study of rituximab (anti-CD20) for refractory systemic lupus erythematosus.  Ann Rheum Dis. 2006;  65 (Suppl II) 360
    CrossrefPubMedGoogle Scholar
  • 59 Tanaka Y, Yamamoto K, Takeuchi T. et al . A multi-center phase I/II trial of rituximab for treatment of refractory systemic lupus erythematosus.  Arthritis Rheum. 2006;  54 (Suppl 9) 258-259 (Abstract 537)
    PubMedGoogle Scholar
  • 60 Tokunaga M, Saito K, Kawabata D. et al . Efficacy of rituximab (Anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system.  Ann Rheum Dis. 2006;  Epub ahead of print
    PubMedGoogle Scholar
  • 61 Torralba K D, Gomez H. Filipino Rituximab Registry Group . Rituximab usage among filipinos with systemic lupus erythematosus.  Ann Rheum Dis. 2005;  64 (Suppl III) 235
    CrossrefPubMedGoogle Scholar
  • 62 Traverse W, Tremazi J, Lakshminarayanan S. Rituximab use in a case of alveolitis and myositis in the context of systemic scleroderma. 69th Annual Scientific Meeting of the American College of Rheumatology, November 12 - 17, 2005, San Diego, USA, CA.  Abstract F101
    PubMedGoogle Scholar
  • 63 Vigna-Perez M, Hernandez-Castro B, Paredes-Saharopulos O. et al . Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study.  Arthritis Res Ther. 2006;  8 (3) R83
    CrossrefPubMedGoogle Scholar
  • 64 Voulgarelis M, Giannouli S, Anagnostou D. et al . Combined therapy with rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) for Sjogren’s syndrome- associated B-cell aggressive non-Hodgkin’s lymphomas.  Rheumatology. 2004;  43 (8) 1050-1053
    CrossrefPubMedGoogle Scholar
  • 65 Willems M, Haddad E, Niaudet P. French Pediatric-Onset SLE Study Group . Rituximab therapy for childhood-onset systemic lupus erythematosus.  J Pediatr. 2006;  148 (5) 623-627
    PubMedGoogle Scholar
  • 66 , www.clinicaltrials.gov
  • 67 Zaja F, De Vita S, Mazzaro C. et al . Efficacy and safety of rituximab in type II mixed cryoglobulinemia.  Blood. 2003;  101 (10) 3827-3834
    CrossrefPubMedGoogle Scholar

Prof. Dr. med. Hubert G. Nüßlein

Medizinische Klinik III, Städt. Klinikum Friedrichstadt

Friedrichstr. 41

01067 Dresden

Phone: ++49/3 51/4 80 14 00

Fax: ++49/3 51/4 80 11 19

Email: nuesslein-hu@khdf.de

      >