PDF herunterladen
Arthritis und Rheuma 2010; 30(01): 45-50
DOI: 10.1055/s-0037-1618008
Therapieoptionen in der Rheumatologie
Schattauer GmbH

Praxis der Cyclophosphamidtherapie in der Rheumatologie

Complexity of Cyclophosphamide treatment in rheumatology
J. Wollenhaupt
1   Abteilung für Rheumatologie und Klinische Immunologie, Schön-Klinik Hamburg-Eilbek, Hamburg, Bremen
,
M. Fleck
2   Klinik für Rheumatologie/klinische Immunologie, Asklepios Klinik Bad Abbach, Rostock, Bremen
,
W. Hartung
2   Klinik für Rheumatologie/klinische Immunologie, Asklepios Klinik Bad Abbach, Rostock, Bremen
,
C. Kneitz
3   Klinik für Innere Medizin II, Klinikum Südstadt, Rostock, Bremen
,
A. Krause
4   Rheumakliniken Berlin-Buch und Berlin Wannsee, Immanuel-Krankenhaus Berlin, Bremen
,
J. Kuipers
5   Klinik für Internistische Rheumatologie, Rotes Kreuz Krankenhaus, Bremen
,
H.-J. Lakomek
6   Klinik für Rheumatologie, Physikalische Medizin und Geriatrie, Klinikum Minden
,
C. Specker
7   Abteilung für Rheumatologie und Klinische Immunologie, Kliniken Essen Süd
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
21. Dezember 2017 (online)

    Lizenzen und Reprints

Zusammenfassung

Auch nach der Einführung vieler neuer immunmodulatorischer Substanzen, wie z. B. den Biologika, hat Cyclophosphamid einen festen Stellenwert in der Behandlung bestimmter entzündlich-rheumatischer Erkrankungen wie der Lupus-Nephritis und anderen organschädigenden Verläufen bei systemischen Vaskulitiden. In dieser Übersichtsarbeit werden die wichtigsten Indikationen zum Einsatz von Cyclophosphamid bei schweren Krankheitsverläufen, sei es zum Krankheitsbeginn oder bei Krankheitsrezidiv, vorgestellt. Mit der Beschreibung wichtiger Erkenntnisse zum Einsatz von Cyclophosphamid sollen Nebenwirkungsrisiken dieser Substanz minimiert und zudem therapiebedingte Langzeitschäden vermieden werden. Daher liegt ein Schwerpunkt dieser Arbeit in der Darstellung der praktischen Durchführung der Cyclophosphamid-Therapie wie auch in der Prophylaxe von Cyclophosphamid-assoziierten Nebenwirkungen. Schließlich wird eine Bewertung der oralen versus parenteralen Applikation wie auch der Abgrenzung des stationären bzw. teilstationären/ambulanten Cyclophosphamid-Einsatzes vorgenommen. Cyclophosphamid bleibt vorerst eine unverzichtbare Substanz im Behandlungsspektrum der Rheumatologie wie auch der klinischen Immunologie.

Summary

Although a couple of new immunomodulatory or immunosuppressive substances, mainly the biologicals, have been established, Cyclophosphamide still plays an important role in the treatment of severe systemic rheumatic diseases such as lupus-nephritis and other systemic vasculitides affecting vital parts. The most important indications concerning severe courses, early stages of disease as well as relapses of disease are presented. Essential acknowledgments in the use of Cyclophosphamide, are described in order to minimize side effects and to avoid long-term damage caused by its application. Therefore, this paper is focused on the description of the practical use of Cyclophosphamide-therapy and on the prevention of Cyclophosphamide-associated side effects. Moreover, different forms of application (oral vs parenteral) and indications for an inpatient use of Cyclophosphamide are evaluated. For the time being Cyclophosphamide remains an indispensable option within the armentarium of rheumatological and immunological treatment.

Schlüsselwörter

Cyclophosphamid - rheumatische Systemerkrankungen - systemische Vaskulitiden - klinische Immunologie - Therapie-Nebenwirkungen

Keywords

Cyclophosphamide - systemic rheumatic diseases - systemic vasculitis - clinical immunology - therapeutic side effects
 

  • Literatur

  • 1 Au K, Khanna D, Clements PJ. et al. Current concepts in disease-modifying therapy for systemic sclerosis-associated interstitial lung disease: Lessons from clinical trials. Curr Rheumatol Rep 2009; 11: 111-119.
    CrossrefGoogle Scholar
  • 2 Austin 3rd HA, Klippel JH, Balow JE. et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986; 314: 614-619.
    CrossrefGoogle Scholar
  • 3 Bertsias G. et al. EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics. Ann Rheum Dis 2008; 67 (02) 195-205.
    CrossrefGoogle Scholar
  • 4 Boumpas DT, Austin 3rd HA, Vaughn EM. et al. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 1992; 340: 741-745.
    CrossrefGoogle Scholar
  • 5 de Groot K, Harper L, Jayne DR. et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibodyassociated vasculitis: A randomized trial. Ann Intern Med 2009; 150: 670-680.
    CrossrefGoogle Scholar
  • 6 de Groot K, Reinhold-Keller E. Wegener's granulomatosis and microscopic polyangiitis. Z Rheumatol 2009; 68: 49-63 quiz 4.
    CrossrefGoogle Scholar
  • 7 Donadio JV, Holley KE, Ferguson RH, Ilstrup DM. Treatment of diffuse proliferative lupus nephritis with prednisone and combined prednisone and cyclophosphamide. N Engl J Med 1978; 299: 1151-1155.
    CrossrefGoogle Scholar
  • 8 Du LT, Fain O, Wechsler B. et al. Value of „Bolus“ Cyclophosphamide injections in behcet's disease. Experience of 17 cases. Presse Med 1990; 19: 1355-1358.
    Google Scholar
  • 9 Flanc RS, Roberts MA, Strippoli GF. et al. Treatment for lupus nephritis. Cochrane Database Syst Rev 2004; CD002922.
    Google Scholar
  • 10 Flanc RS, Roberts MA, Strippoli GF. et al. Treatment of diffuse proliferative lupus nephritis: A metaanalysis of randomized controlled trials. Am J Kidney Dis 2004; 43: 197-208.
    CrossrefGoogle Scholar
  • 11 Gayraud M, Guillevin L, Cohen P. et al. Treatment of good-prognosis polyarteritis nodosa and churg-strauss syndrome: Comparison of steroids and oral or pulse cyclophosphamide in 25 patients. French cooperative study group for vasculitides. Br J Rheumatol 1997; 36: 1290-1297.
    CrossrefGoogle Scholar
  • 12 Gayraud M, Guillevin L, le Toumelin P. et al. Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and churg-strauss syndrome: Analysis of four prospective trials including 278 patients. Arthritis Rheum 2001; 44: 666-675.
    CrossrefGoogle Scholar
  • 13 Gourley MF, Austin 3rd HA, Scott D. et al. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Ann Intern Med 1996; 125: 549-557.
    CrossrefGoogle Scholar
  • 14 Guillevin L, Lhote F, Cohen P. et al. Corticosteroids plus pulse cyclophosphamide and plasma exchanges versus corticosteroids plus pulse cyclophosphamide alone in the treatment of polyarteritis nodosa and churg-strauss syndrome patients with factors predicting poor prognosis. A prospective, randomized trial in sixty-two patients. Arthritis Rheum 1995; 38: 1638-1645.
    CrossrefGoogle Scholar
  • 15 Guillevin L, Lhote F. Treatment of polyarteritis nodosa and churg-strauss syndrome: Indications of plasma exchanges. Transfus Sci 1994; 15: 371-388.
    CrossrefGoogle Scholar
  • 16 Hamza M, Meddeb S, Mili I, Ouertani A. Bbolus of cyclophosphamide and methylprednisolone in uveitis in behcet's disease. Preliminary results with the use of new criteria of evaluation. Ann Med Interne (Paris) 1992; 143: 438-441.
    Google Scholar
  • 17 Hoffman GS, Kerr GS, Leavitt RY. et al. Wegener granulomatosis: An analysis of 158 patients. Ann Intern Med 1992; 116: 488-498.
    CrossrefGoogle Scholar
  • 18 Houssiau F. Thirty years of cyclophosphamide: assessing the evidence. Lupus 2007; 16: 212-216.
    CrossrefGoogle Scholar
  • 19 Hoyles RK, Ellis RW, Wellsbury J. et al. A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum 2006; 54: 3962-3970.
    CrossrefPubMedGoogle Scholar
  • 20 Illei GG, Austin HA, Crane M. et al. Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Ann Intern Med 2001; 135: 248-257.
    CrossrefGoogle Scholar
  • 21 Kazokoglu H, Saatci O, Cuhadaroglu H, Eldem B. Long-term effects of cyclophosphamide and colchicine treatment in behcet's disease. Ann Ophthalmol 1991; 23: 148-151.
    Google Scholar
  • 22 Khanna D, Yan X, Tashkin DP. et al. Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: Results from the scleroderma lung study. Arthritis Rheum 2007; 56: 1676-1684.
    CrossrefGoogle Scholar
  • 23 Lakomek HJ. Brauchen wir eine stationäre Rheumatologie?. Dtsch Med Wochenschr 2006; 131: 2292-2294.
    Artikel in Thieme ConnectGoogle Scholar
  • 24 Lakomek HJ, Neeck G, Lang B, Jung J. Strukturqualität akut-internistischer rheumatologischer Kliniken – Projektgruppenarbeit des VRA. ZRheumatol 2002; 61 (04) 405-414.
    Google Scholar
  • 25 Leib ES, Restivo C, Paulus HE. Immunosuppressive and corticosteroid therapy of polyarteritis nodosa. Am J Med 1979; 67: 941-947.
    CrossrefGoogle Scholar
  • 26 Marder W, Christman GM, Ognenovski V, McCune WJ. Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus. Arthritis Rheum 2005; 52: 2761-2767.
    CrossrefGoogle Scholar
  • 27 Moyo VM, Smith D, Brodsky I. et al. High-dose cyclophosphamide for refractory autoimmune hemolytic anemia. Blood 2002; 100: 704-706.
    CrossrefGoogle Scholar
  • 28 Murphy S, LoBuglio AF. Drug therapy of autoimmune hemolytic anemia. Semin Hematol 1976; 13: 323-334.
    Google Scholar
  • 29 Nachman PH, Hogan SL, Jennette JC, Falk RJ. Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol 1996; 7: 33-39.
    Google Scholar
  • 30 Ozyazgan Y, Yurdakul S, Yazici H. et al. Low dose cyclosporin a versus pulsed cyclophosphamide in behcet's syndrome: A single masked trial. Br J Ophthalmol 1992; 76: 241-243.
    CrossrefGoogle Scholar
  • 31 Panceri R, Fraschini D, Tornotti G. et al. Successful use of high-dose cyclophosphamide in a child with severe autoimmune hemolytic anemia. Haematologica 1992; 77: 76-78.
    Google Scholar
  • 32 Saenz A, Ausejo M, Shea B. et al. Pharmacotherapy for behcet's syndrome. Cochrane Database Syst Rev 2000; CD001084.
    Google Scholar
  • 33 Silva VA, Seder RH, Weintraub LR. Synchronization of plasma exchange and cyclophosphamide in severe and refractory autoimmune hemolytic anemia. J Clin Apher 1994; 9: 120-123.
    CrossrefGoogle Scholar
  • 34 Steinberg AD, Decker JL. A double-blind controlled trial comparing cyclophosphamide, azathioprine and placebo in the treatment of lupus glomerulonephritis. Arthritis Rheum 1974; 17: 923-937.
    CrossrefGoogle Scholar
  • 35 Steinberg AD. The treatment of lupus nephritis. Kidney Int 1986; 30: 769-787.
    CrossrefGoogle Scholar
  • 36 Tashkin DP, Elashoff R, Clements PJ. et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006; 354: 2655-2666.
    CrossrefPubMedGoogle Scholar
  • 37 Tashkin DP, Elashoff R, Clements PJ. et al. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am J Respir Crit Care Med 2007; 176: 1026-1034.
    CrossrefGoogle Scholar
  • 38 Travis LB, Curtis RE, Glimelius B. et al. Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma. J Natl Cancer Inst 1995; 87: 524-530.
    CrossrefGoogle Scholar