Mycophenolate mofetil in the treatment of non-renal manifestations of systemic lupus erythematosus: recent insights

Year 2010, Volume: 12 Issue: 1, 104 - 108, 01.03.2010

Ali Şahin

Abstract

Mycophenolate mofetil (MMF) is an immunosuppressive agent that has been shown to beeffective in transplant patients. It is also efficacious in the management of lupus nephritis, anduseful in the treatment of autoimmune conditions as its mechanisms of action target the T- andB – lymphocytes, leading to suppression of the cell-mediated 3immune responses and antibodyformation. It has been used successfully in immune-mediated conditions like myasthenia gravis,autoimmune hepatitis and immune cytopenias. However, its optimal use in non-renalmanifestations (hematological, neuropsychiatric, myocardial, pulmonary, cutaneous etc.) inlupus patients is unclear. There are yet to be randomised controlled trials to guide the optimaldoses and durations of MMF in such situations. MMF is well tolerated and safe to use, thoughthere are reports of serious adverse effects like urticaria, myopathy, Epstein-Barr virus-associatedB-cell lymphoma, cytomegalovirus infections and disseminated varicella zoster. Another areaof concern for patients is the increased cost of using long-term MMF

Keywords

systemic lupus erythematosus, mycophenolate mofetil, treatment

Sistemik Lupus Eritematozus’un Böbrek Dışı Tutulumlarının Tedavisinde Mikofenolat Mofetil: Son Görüşler

Abstract

Mikofenolat mofetil (MMF) transplant hastalarında etkinliği gösterilmiş bir immünsüpresifajandır. Lupus nefriti ve diğer otoimmün hastalıkların tedavisinde; T ve B lenfositleri hedef alanetki mekanizmasına bağlı olarak, hücresel immün yanıtı ve antikor oluşumunu baskıladığıgösterilmiştir. Myastenia gravis, otoimmün hepatit, immün sitopeniler gibi otoimmünhastalıklarda başarıyla kullanılmaktadır. Fakat, lupus hastalarında böbrek dışı tutulumlarda(hematolojik, nöropsikiyatrik, miyokardiyal, pulmoner, kütanöz vb.) optimal kullanımı kesinlikkazanmamıştır. Bu durumlarda kullanımında optimal doz ve süreye dair yol gösterici randomizekontrollü çalışma henüz bulunmamaktadır. MMF iyi tolere edilmesi ve kullanımı güvenliolmasına rağmen; ürtiker, miyopati, Epstein-Barr virüs ilişkili B-hücreli lenfoma,sitomegalovirüs enfeksiyonları ve dissemine varisella zoster gibi birtakım yan etkilerbildirilmiştir. MMF’in uzun süreli kullanımında hastalar için önemli olan bir diğer noktada artanmaliyetidir

Keywords

sistemik lupus eritematozus, mikofenolat mofetil, tedavi

References

• McMurray RW, Harisdangkul V: Mycophenolate mofetil: selective T cell inhibition. Am J Med Sci 323:94-6, 2002.
• Allison AC, Eugui EM: Mycophenolate mofetil and in mechanisms of action. Immunopharmacology 47:85-118, 2000.
• Allison AC: Mechanisms of action of mycophenolate mofetil. Lupus 14:2-8, 2005.
• Lang P, Pardon A, Audard V: Long-term benefit of mycophenolate mofetil in renal transplantation. Transplantation 79:47-8, 2005.
• Garcia VD, Keitel E, Santos AF, et al: Immunosuppression in pancreas transplantation: mycophenolate mofetil versus sirolimus. Transplant Proc 36:975-7, 2004.
• Pierini A, Mirabella S, Brunati A, Ricchiuti A, Franchello A, Salizzoni M: Mycophenoltae mofetil monotherapy in liver transplantation. Transplant Proc 37:2614-5, 2005.
• Klupp J, Pfitzmann R, Langrehr JM, Neuhaus P: Indications of mycophenolate mofetil in liver transplantation. Transplantation 80:5142-6, 2005.
• Kobashigawa JA, Meiser BM: Review of major clinical trials with mycophenolate mofetil in cardiac transplantation. Transplantation 80:235-43, 2005.
• Sanchez V, Delgado JF, Morales JM, et al: Chronic cyclosporine-induced nephrotoxicity in heart transplant patients long-term benefits of treatment with mycophenolate mofetil and low-dose cyclosporine. Transplant Proc 36:2823- 5, 2004.
• Badid C, Desmouliere A, Laville M: Mycophenolate mofetil: implications for the treatment of glomerular disease. Nephrol Dial Transplant 16:1752-1756, 2001.
• Choi MJ, Eustace JA, Gimenez LF et al: Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int 61:1098-1114, 2002.
• Harzallah K, Badid C, Fouque D et al: Efficacy of mycophenolate mofetil on recurrent glomerulonephritis after renal transplantation. Clin Nephrol 59:212-216, 2003.
• Briggs WA, Choi MJ, Scheel PJ: Successful mycophenolate mofetil treatment of glomerular disease. Am J Kidney Dis 31:213-217, 1998.
• Romero F, Rodriguez B-Iturbe, Parra G et al: Mycophenolate mofetil prevents the progressive renal failure induced by 5/6 renal ablation in rats. Kidney Int 55:945-955, 1999.
• Zandman-Goddard G, Shoenfeld Y: Mycophenolate mofetil in animal models of autoimmune disease. Lupus 14:12-6, 2005.
• Cahoon WD Jr, Kockler DR: Mycophenolate mofetil treatment of myasthenia gravis. Ann Pharmacother 40:295-8, 2006.
• Prakash KM, Ratnagopal P, Puvanendran K, Lo YL: Mycophenolate mofetil–as an adjunctive immunosuppressive therapy in refractory myasthenia gravis:The Singapore experience. J. Clin. Neurosci. 14: 278–281, 2006.
• Gorson KC, Amato AA, Ropper AH: Efficacy of Mycophenolate mofetil in patients with chronic immune demyelinating polyneuropathy. Neurology 63:715-7, 2004.
• Chatur N, Ramji A, Bain VG, et al: Transplant immunosuppressive agents in non-transplant chronic autoimmune hepatitis: the Canadian association for the study of liver (CASL) experience with Mycophenolate mofetil and tacrolimus. Liver Int 25:723-7, 2005.
• Devlin SM, Swain MG, Urbanski SJ, Burak KW: Mycophenolate mofetil for the treatment of autoimmune hepatitis in patients refractory to Standard therapy. Can J Gastroenterol 18:321-6, 2004.
• Hou M, Peng J, Shi Y, et al: Mycophenolate mofetil (MMF) for the treatment of steroid –resistant idiopathic thrombocytopenic purpura. Eur J Hematol 70:353-7, 2003.
• Lin JT, Wang WS, Yen CC, et al: Myelodisplastic syndrome complicated by autoimmune hemolytic anemia: remission of refractory anemia following Mycophenolate mofetil. Ann Hematol 81:723-6, 2002.
• Zimmer-Molsberger B, Knauf W, Thief E: Mycophenolate mofetil for severe autoimmune hemolytic anemia. Lancet 350:1003-4, 1997.
• Majithia V, Harisdangkul V: Mycophenolate mofetil (Cellcept): an alternative therapy for autoimmune inflammatory myopathy. Rheumatology 44:386-9, 2005.
• Schrader P, Mooser G, Peter RU, Puhl W: Preliminary results in the therapy of psoriatic arthritis with Mycophenolate mofetil. Z Rheumatol 61:545-50, 2002.
• Karim MY, Abbs IC: Mycophenolate mofetil in nonlupus glomerulonephropathy. Lupus 14:39-41, 2005.
• Ierardi E, Rendina M, Francavilla R, et al: Mycophenolate mofetil in the treatment of autoimmune HCV-associated hematological disorders showing steroid resistance or dependence. J Viral Hepat 10:390-3, 2003.
• Koukoulaki M, Jayne DR: Mycophenolate mofetil in anti- neutrophil cytoplasm antibodies-associated systemic vasculitis. Nephron Clin Pract 102:100-7, 2006.
• Nousari HC, Sragovich A, Kimyasi-Asadi A, Orlinsky D, Anhalt GJ: Mycophenolate mofetil in autoimmune and inflammatory skin disorders. J Am Acad Dermatol 40:265-8, 1999.
• Fong KY, Thumboo J, Koh ET, et al: Systemic lupus erythematosus: initial manifestations and clinical features after 10 years of disease. Ann Acad Med Singapore 26:278- 81, 1997.
• Alsaeid K, Kamal H, Haider MZ, Al-Enezi HM, Malaviya AN: Systemic lupus erythematosus in Kuwaiti children: organ system involvement and serological findings. Lupus 13:613- 7, 2004.
• Mok CC, Lau CS: Lupus in Hong Kong Chinese. Lupus 12:717-22, 2003.
• Vasoo S, Thumboo J, Fong KY: Refractory immune thrombocytopenia in systemic lupus erythematosus: response to mycophenolte mofetil. Lupus 12:603-2, 2003.
• Chang HK: Successful tretament of refractory thrombocytopenia with mycophenolate mofetil in a patient with systemic lupus erythematosus. J Korean Med Sci 20:883- 5, 2005.
• Alba P, Karim MY, Hunt BJ: Mycophenolate mofetil as a treatment for autoimmune hemolytic anaemia in patients with systemic lupus erythematosus and antiphospholipid syndrome. Lupus 12:633-5, 2003.
• Mak A, Mok CC: Mycophenolate mofetil for refractory hemolytic anaemia in systemic lupus erythematosus. Lupus 14:856-8, 2005.
• Arcasoy MO, Chao NJ: T-cell mediated pure red-cell aplasia in systemic lupus erythematosus: response to cyclosporine A and Mycophenolate mofetil. Am J Hematol 78:161-3, 2005.
• Jose J, Paulose BK, Vasuki Z, Danda D: Mycophenolate mofetil in neuropsychiatric systemic lupus erythematosus. Indian J Med Sci 59:353-6, 2005.
• Lhotta K, Wurzner R, Rosenkranz AR, et al: Cerebral vasculitis in a patient with hereditary complete C4 deficiency and systemic lupus erythematosus. Lupus 13:139-41, 2004.
• Mok CC, Mak A, To CH: Mycophenolate mofetil for lupus related myelopathy. Ann rheum Dis 5:971-3, 2006.
• Samad AS, Lindsley CB: Treatment of pulmonary hemorrhage in childhood systemic lupus erythematosus with Mycophenolate mofetil. South Med J 96:705-7, 2003.
• Swigris JJ, Olson AL, Fischer A, et al: Mycophenolate mofetil is afe, well tolarated,and preserves lung function in patients with connective tissue disease-related interstitial lung disease. Chest 130:30-6, 2006.
• Kamiyoshi Y, Takahashi M, Yokoseki O, et al: Mycophenolate mofetil prevents the development of experimental autoimmune myocarditis. J Mol Cell Cardiol 39:467-77, 2005.
• Lambotte O, Khellaf M, Harmouche H, et al: Characteristics and long-term outcome of 15 episodes of systemic lupus erythematosus-associated hemophagocytic syndrome. Medicine (Baltimore) 85:169-82, 2006.
• Goyal S, Nousari HC: Treatment of resistant discoid lupus erythematosus of the palms and soles with Mycophenolate mofetil. J Am Acad Dermatol 45:142-4, 2001.
• Schanz S, Ulmer A, Rassner G, Fierlbeck G: Successful treatment of subacute cutaneous lupus erythematosus with Mycophenolate mofetil. Br J Dermatol 147:174-8, 2002.
• Hanjani NM, Nousari HC: Mycophenolate mofetil for the treatment of cutaneous lupus erythematosus with smoldering systemic involvement. 138:1616-8, 2002.
• Pisoni CN, Obermoser G, Cuadrado Mj, et al: Skin manifestations of systemic lupus erythematosus refractory to multiple treatment modalities: poor results with Mycophenolate mofetil. Clin Exp Rheumatol 23:393-6, 2005.
• Riskalla MM, Somers EC, Fatica RA, McCune WJ: Tolerability of Mycophenolate mofetil in patients with systemic lupus erythematosus. J Rheumatol 30:1508-12, 2003.
• Pisoni CN, Sanchez FJ, Karim Y, et al: Mycophenolate mofetil in systemic lupus erythematosus: efficacy and tolerability in 86 patients. J Rheumatol 32:1047-52, 2005.
• Karim MY, Alba P, Cuadrado MJ: Mycophenolate mofetil for systemic lupus erythematosus refractory to other immunosuppressive agents. Rheumatology (Oxford) 41:876- 82, 2002.
• Szyper-Kravitz M, Sheinberg P, Sidi Y, Schiffenbauer Y, Trubniykov E, Shoenfeld Y: Hypersensitivity to Mycophenolate mofetil in systemic lupus erythematosus: diagnostic measures and successful desensitization. Int Arch Allergy Immunol 138:334-6, 2005.
• Galindo M, Cabello A, Joven B: Mycophenolate mofetil induced myopathy in a patient with lupus nephritis. J Rheumatol 32:188-90, 2005.
• Waldman MA, Callen JP: Self-resolution of Epstein-Barr virus-associated B-cell lymphoma in a patient with dermatomyositis following withdrawal of Mycophenolate mofetil and methotrexate. J Am Acad Dermatol 51:124-30, 2004.
• Woywodt A, Choi M, Schneider W, Kettritz R, Gobel U: Cytomegalovirus colitis during Mycophenolate mofetil therapy for Wegener’s granulomatosis. Am J Nephrol 20:468- 72, 2000.
• Song AT, Abdala E, Bonazzi PR, Bacchella T, Machado MC: Does Mycophenolate mofetil increase the risk of cytomegalovirus infection in solid organ transplant recipients? – A mini-review. Braz J Infect Dis 10:132-8, 2006.
• Rothwell WS, Gloor JM, Morgerstern BZ, Milliner DS: Disseminated varicella infection in pediatric renal transplant recipients treated with Mycophenolate mofetil. Transplantation 68:158-61, 1999.
• Lauzurica R, Bayes B, Frias C, et al: Disseminated varicella infection in adult renal allograft recipients: role of Mycophenolate mofetil. Transplant Proc 35:1758-9, 2003.
• The Tricontinental Mycophenolate mofetil Renal Transplantation Study Group: A blinded, randomized clinical trial of Mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 61:1029-37, 1996.