Immunsuppressive Therapie - Myasthenia gravis

Zur Therapie der Myasthenia gravis stehen eine Reihe gut wirksamer Immunsuppressiva zur Verfügung, die im längerfristigen Verlauf helfen, Steroide einzusparen und damit eine Remission unter möglichst minimalen Nebenwirkungen aufrecht zu erhalten. Die Indikationsstellung zur immunsuppressiven Therapie orientiert sich an der Erkrankungsschwere und Verlaufsdynamik unter Berücksichtigung des Effektes einer evtl. erfolgten Thymektomie. Zugelassen ist zur Myastheniebehandlung derzeit lediglich Azathioprin, sodass andere Substanzen wie Ciclosporin A, Mycophenolatmofetil, Cyclophosphamid und Tacrolimus im Einzelfall off-label verordnet werden müssen.

Immunosuppressive therapy of myasthenia gravis is important for long-term maintenance of remission with minimal side effects. Indication for immunosuppressive treatment is dependent on the severity and course of the disease, and has to take into account the effect of thymectomy which is eventually performed in early-onset generalized myasthenia. Azathioprin is the only drug formally approved for treatment of myasthenia. However, a variety of other immunosuppressants, such as cyclosporine, mycophenolate, cyclophosphamide, and tacrolimus, have also been shown to be effective and can be prescribed off-label as second-line treatment in cases with inefficacy or intolerable side effects of azathioprine.

Key words

myastenia gravis - azathioprin - ciclosporine - cyclophosphamide -

Literatur

• 1 Allison AC, Kowalski WJ, Muller CD, Eugui EM.. Mechanisms of action of mycophenolic acid.  Ann N Y Acad Sci. 1993;  696 63-87
• 2 Behrend M, Lueck R, Pichlmayr R.. Long-term experience with mycofenolate mofetil in the prevention of renal allograft rejection.  Transplant Proc. 1997;  29 2927-2929
• 3 Chaudhry V, Cornblath DR, Griffin JW, O'Brien R, Drachman DB.. Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases.  Neurology. 2000;  56 94-96
• 4 Ciafaloni E, Massey JM, Tucker-Lipscomb B, Sanders DB.. Mycophenolate mofetil for myasthenia gravis: an open-label pilot study.  Neurology. 2000;  56 97-99
• 5 de Feo LG, Schottlender J, Martelli NA, Molfino NA.. Use of intravenous pulsed cyclophosphamide in severe, generalized myasthenia gravis.  Muscle Nerve. 2002;  26 31-36
• 6 Drachman DB, Jones RJ, Brodsky RA.. Treatment of refractory myasthenia: „Rebooting” with high-dose cyclophosphamide.  Ann Neurol. 2003;  53 29-34
• 7 Drachman DB.. Myasthenia gravis.  N Engl J Med. 1994;  330 1797-1810
• 8 Evoli A, Batocchi AP, Minisci C, Di C Schino, Tonali P.. Therapeutic options in ocular myasthenia gravis.  Neuromuscul Disord. 2001;  11 208-216
• 9 Evoli A, Di SC, Marsili F, Punzi C.. Successful treatment of myasthenia gravis with tacrolimus.  Muscle Nerve. 2002;  25 111-114
• 10 Gajra A, Vajpayee N, Grethlein SJ.. Response of myasthenia gravis to rituximab in a patient with non-Hodgkin lymphoma.  Am J Hematol. 2004;  77 196-197
• 11 Gladstone DE, Brannagan III TH, Schwartzman RJ, Prestrud AA, Brodsky I.. High dose cyclophosphamide for severe refractory myasthenia gravis.  J Neurol Neurosurg Psychiatry. 2004;  75 789-791
• 12 Gronseth GS, Barohn RJ.. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.  Neurology. 2000;  55 7-15
• 13 Hauser RA, Malek AR, Rosen R.. Successful treatment of a patient with severe refractory myasthenia gravis using mycophenolate mofetil.  Neurology. 1998;  51 912-913
• 14 Hohlfeld R, Toyka KV, Besinger UA, Gerhold B, Heininger K.. Myasthenia gravis: reactivation of clinical disease and of autoimmune factors after discontinuation of long-term azathioprine.  Ann Neurol. 1985;  17 238-242
• 15 Konishi T, Yoshiyama Y, Takamori M, Saida T.. Long-term treatment of generalised myasthenia gravis with FK506 (tacrolimus).  J Neurol Neurosurg Psychiatry. 2005;  76 448-450
• 16 Lanska DJ.. Indications for thymectomy in myasthenia gravis.  Neurology. 1990;  40 1828-1829
• 17 Meriggioli MN, Ciafaloni E, Al KA Hayk, Rowin J, Tucker-Lipscomb B, Massey JM, Sanders DB.. Mycophenolate mofetil for myasthenia gravis: an analysis of efficacy, safety, and tolerability.  Neurology. 2003;  61 1438-1440
• 18 Meriggioli MN, Rowin J, Richman JG, Leurgans S.. Mycophenolate mofetil for myasthenia gravis: a double-blind, placebo-controlled pilot study.  Ann N Y Acad Sci. 2003;  998 494-499
• 19 Meriggioli MN, Rowin J.. Treatment of myasthenia gravis with mycophenolate mofetil: a case report.  Muscle Nerve. 2000;  23 1287-1289
• 20 Mertens HG, Balzereit F, Leipert M.. The treatment of severe myasthenia gravis with immunosuppressive agents.  Eur Neurol. 1969;  2 321-329
• 21 Mowzoon N, Sussman A, Bradley WG.. Mycophenolate (CellCept) treatment of myasthenia gravis, chronic inflammatory polyneuropathy and inclusion body myositis.  J Neurol Sci. 2001;  185 119-122
• 22 Nagane Y, Utsugisawa K, Obara D, Kondoh R, Terayama Y.. Efficacy of low-dose FK506 in the treatment of Myasthenia gravis - a randomized pilot study.  Eur Neurol. 2005;  53 146-150
• 23 Newsom-Davis J.. Can tacrolimus replace ciclosporin and prednisone to treat myasthenia gravis?.  Nat Clin Pract Neurol. 2005;  1 14-15
• 24 Palace J, Newsom-Davis J, Lecky B.. Myasthenia Gravis Study Group. . A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis.  Neurology. 1998;  50 1778-1783
• 25 Ponseti JM, Azem J, Fort JM, Lopez-Cano M, Vilallonga R, Buera M, Cervera C, Armengol M.. Long-term results of tacrolimus in cyclosporine- and prednisone-dependent myasthenia gravis.  Neurology. 2005;  64 1641-1643
• 26 Richman DP, Agius MA.. Treatment of autoimmune myasthenia gravis.  Neurology. 2003;  61 1652-1661
• 27 Sanders DB, Aarli JA, Cutter GR, Jaretzki III A, Kaminski HJ, Phillips LH.. Long-term results of tacrolimus in cyclosporine- and prednisone-dependent myasthenia gravis.  Neurology. 2006;  66 954-955
• 28 Schneider C, Gold R, Reiners K, Toyka KV.. Mycophenolate mofetil in the therapy of severe myasthenia gravis.  Eur Neurol. 2001;  46 79-82
• 29 Schneider-Gold C, Hartung HP, Gold R.. Mycophenolate mofetil and tacrolimus: new therapeutic options in neuroimmunological diseases.  Muscle Nerve. 2006;  34 284-291
• 30 Thakre M, Inshasi J, Marashi M.. Rituximab in refractory MuSK antibody myasthenia gravis. J Neurol 2007
• 31 Tindall RS, Rollins JA, Phillips JT, Greenlee RG, Wells L, Belendiuk G.. Preliminary results of a double-blind, randomized, placebo-controlled trial of cyclosporine in myasthenia gravis.  N Engl J Med. 1987;  316 719-724
• 32 Vincent A.. Unravelling the pathogenesis of myasthenia gravis.  Nat Rev Immunol. 2002;  2 797-804
• 33 Wylam ME, Anderson PM, Kuntz NL, Rodriguez V.. Successful treatment of refractory myasthenia gravis using rituximab: a pediatric case report.  J Pediatr. 2003;  143 674-677
• 34 Zaja F, Russo D, Fuga G, Perella G, Baccarani M.. Rituximab for myasthenia gravis developing after bone marrow transplant.  Neurology. 2000;  55 1062-1063

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