Zusammenfassung
Hintergrund: Bei Patienten nach Risikokeratoplastik stehen bislang nur Ciclosporin A (CSA) und Mycophenolatmofetil (MMF) für eine systemische Immunsuppression zur Verfügung. Basiliximab ist ein chimerer monoklonaler Interleukin-2-Rezeptor Antikörper, der die T-Zell-Proliferation nachhaltig inhibiert und für die Nachbehandlung nierentransplantierter Patienten zugelassen ist. Ziel dieser Studie war es, die Sicherheit und Effektivität einer systemischen Immunsuppression mit Basiliximab zur Verhinderung der Abstoßungsreaktion nach Risikokeratoplastik zu untersuchen. Patienten und Methoden: 20 Patienten nach Risikokeratoplastik erhielten als postoperative Basistherapie Fluocortolon 1 mg/kg/d, über drei Wochen ausschleichend sowie lokal Prednisolonacetat 5 ×/d über fünf Monate ausschleichend. Zusätzlich erhielten 10 Patienten am Operationstag sowie vier Tage postoperativ 20 mg Basiliximab intravenös. Die zehn Patienten der Kontrollgruppe erhielten CSA talspiegeladaptiert (Zielspiegel 120 - 150 ng/mL) über ein halbes Jahr. Ergebnisse: Nach einer mittleren Nachbeobachtungszeit von 477 ± 263 Tagen zeigten sich bei 4 Patienten der Basiliximabgruppe Immunreaktionen, von denen zwei nach Kortisontherapie reversibel waren. Nebenwirkungen wurden keine beobachtet. In der CSA-Gruppe traten 2 Abstoßungsreaktionen auf (eine reversible und eine irreversible). Allerdings musste bei 2 Patienten der Gruppe 2 die Medikamenteneinnahme aufgrund von Nebenwirkungen abgebrochen werden. Schlussfolgerungen: Basiliximab zeigte eine etwas schwächere Wirksamkeit bei der Verhinderung von Immunreaktionen nach Risikokeratoplastik als CSA. Die Therapie mit Basiliximab zeigte in dieser Studie keine Nebenwirkungen.
Abstract
Background: Until now cyclosporin A (CSA) and mycophenolate mofetil (MMF) are the only available systemic immunosuppressants for patients undergoing risk keratoplasty. Basiliximab is a chimeric monoclonal interleukin 2-receptor antibody, which inhibits T-cell proliferation. Basiliximab is approved for the treatment in patients after kidney transplantation. The aim of this study was to prove the efficacy and safety of Basiliximab after penetrating risk keratoplasty. Patients and Methods: 20 patients undergoing risk keratoplasty received as postoperative medication fluocortolon 1 mg/kg/d (tapered off within three weeks) and prednisolone acetate eye-drops 5x/d (tapered off within five months). In addition, 10 patients received 20 mg basiliximab immediately following surgery and four days postoperatively. 10 patients in the control group received oral CSA adapted to the blood-trough level (120 - 150 ng/mL) for six months. Results: After a mean follow-up time of 477 ± 263 days 4 patients of the basiliximab group showed corneal immune reactions (2 irreversible), while no side effects were observed. In the CSA group 2 immune reactions occurred (1 irreversible). In 2 CSA-treated patients the CSA administration had to be stopped due to side effects. Conclusions: Basiliximab has a lower efficacy in preventing immune reactions after risk keratoplasty than CSA. However, the side effect profile of basiliximab is more favourable than that of CSA.
Schlüsselwörter
perforierende Keratoplastik - Immunsuppression - Basiliximab
Key words
penetrating keratoplasty - immunosuppression - basiliximab
Literatur
1
Alldredge O C, Krachmer J H.
Clinical types of corneal transplant rejection. Their manifestations, frequency, preoperative correlates, and treatment.
Arch Ophthalmol.
1981;
99
599-604
2
Bertelmann E, Reinhard T, Pleyer U.
Current practice of immune prophylaxis and therapy in perforating keratoplasty. A survey of members of the Cornea Section of the German Ophthalmological Society.
Ophthalmologe.
2003;
100
1031-1035
3
Birnbaum F, Böhringer D, Sokolovska Y. et al .
Immunosuppression with cyclosporine a and mycophenolate mofetil after penetrating high-risk keratoplasty: a retrospective study.
Transplantation.
2005;
79
964-968
4
Birnbaum F, Maier P, Reinhard T.
Intracameral application of corticosteroids for treating severe endothelial rejection after penetrating keratoplasty.
Ophthalmologe.
2007;
104
813-816
5
Birnbaum F, Reis A, Böhringer D. et al .
An open prospective pilot study on the use of rapamycin after penetrating high-risk keratoplasty.
Transplantation.
2006;
81
767-772
6
Birnbaum F, Reis A, Reinhard T.
Immunosuppression following penetrating keratoplasty.
Ophthalmologe.
2007;
104
371-372
7
Hill J C.
Systemic cyclosporine in high-risk keratoplasty. Short- versus long-term therapy.
Ophthalmology.
1994;
101
128-133
8
Hill J C.
Immunosuppression in corneal transplantation.
Eye.
1995;
9 (Pt 2)
247-253
9
Hoffmann F.
Suture technique for perforating keratoplasty (author’s transl).
Klin Monatsbl Augenheilkd.
1976;
169
584-590
10
Kahan B D, Rajagopalan P R, Hall M. United States Simulect Renal Study Group .
Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody.
Transplantation.
1999;
67
276-284
11
Kaplan E L, Meier P.
Nonparametric estimation from incomplete observations.
J Am Stat Assoc.
1958;
53
457-481
12
Nashan B, Moore R, Amlot P. CHIB 201 International Study Group. .
Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients.
Lancet.
1997;
350
1193-1198
13
Pleyer U, Weidle E G, Lisch W. et al .
Clinical types of immunologic transplant reactions following perforating keratoplasty.
Fortschr Ophthalmol.
1990;
87
14-19
14
Reinhard T, Böhringer D, Enczmann J. et al .
Improvement of graft prognosis in penetrating normal-risk keratoplasty by HLA class I and II matching.
Eye.
2004;
18
269-277
15
Reinhard T, Hutmacher M, Sundmacher R.
Acute and chronic immune reactions after penetrating keratoplasty with normal immune risk.
Klin Monatsbl Augenheilkd.
1997;
210
139-143
16
Reinhard T, Mayweg S, Sokolovska Y. et al .
Systemic mycophenolate mofetil avoids immune reactions in penetrating high-risk keratoplasty: preliminary results of an ongoing prospectively randomized multicentre study.
Transpl Int.
2005;
18
703-708
17
Reinhard T, Reis A, Böhringer D. et al .
Systemic mycophenolate mofetil in comparison with systemic cyclosporin A in high-risk keratoplasty patients: 3 years’ results of a randomized prospective clinical trial.
Graefes Arch Clin Exp Ophthalmol.
2001;
239
367-372
18
Reinhard T, Spelsberg H, Henke L. et al .
Long-term results of allogeneic penetrating limbo-keratoplasty in total limbal stem cell deficiency.
Ophthalmology.
2004;
111
775-782
19
Reinhard T, Sundmacher R, Godehardt E. et al .
Preventive systemic cyclosporin A after keratoplasty at increased risk for immune reactions as the only elevated risk factor.
Ophthalmologe.
1997;
94
496-500
20
Reinhard T, Sundmacher R, Heering P.
Systemic ciclosporin A in high-risk keratoplasties.
Graefes Arch Clin Exp Ophthalmol.
1996;
234 (Suppl 1)
S115-S121
21
Reis A, Birnbaum F, Reinhard T.
Systemic immunosuppressives after penetrating keratoplasty.
Ophthalmologe.
2007;
104
373-380
22
Schmitz K, Hitzer S, Behrens-Baumann W.
Immune suppression by combination therapy with basiliximab and cyclosporin in high risk keratoplasty. A pilot study.
Ophthalmologe.
2002;
99
38-45
Dr. Florian Birnbaum
Augenklinik, Universitätsklinik Freiburg
Killianstr. 5
79106 Freiburg
Phone: ++ 4 97 61/2 70 40 01
Fax: ++ 4 97 61/2 70 40 63
Email: florian.birnbaum@uniklinik-freiburg.de