Skip to main content
Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 6/2008

01.06.2008 | Inflammatory Disorders

Ocular toxicity of intravitreous adalimumab (Humira) in the rabbit

verfasst von: Roberta P. A. Manzano, Gholam A. Peyman, Petros E. Carvounis, Muhamet Kivilcim, Palwasha Khan, Patricia Chevez-Barrios, Walter Takahashi

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 6/2008

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To evaluate the ocular toxicity of escalating doses of intravitreous adalimumab (Humira) in the rabbit eye.

Methods

Twelve New Zealand albino rabbits received unilateral intravitreous injections of 0.1 ml of adalimumab 0.25 mg (three eyes), 0.50 mg (three eyes), 1.0 mg (three eyes) or 0.1 ml balanced salt solution (BSS, threeeyes). Slit-lamp biomicroscopy and fundoscopy were carried out at baseline, day 1, 7 and 14 following intravitreous injection, while electroretinography (ERG) was carried out at baseline and day 14. Animals were euthanized on day 14, and histopathological examination of the eyes was performed.

Results

Slit-lamp biomicroscopy and fundoscopy were normal in eyes having received BSS, 0.25 mg or 0.50 mg adalimumab; however, inflammation was present in two of three eyes having received 1.0 mg adalimumab. Similarly, comparison of scotopic and photopic ERG light at baseline and day 14 demonstrated no changes in eyes receiving BSS, 0.25 mg or 0.50 mg adalimumab, but two of three eyes having received 1.0 mg adalimumab showed a greater than 30% reduction in a and b wave. Finally, histopathology demonstrated no differences between eyes receiving BSS, 0.25 mg or 0.50 mg of adalimumab, but two of three eyes injected with 1.0 mg demonstrated inflammatory cell infiltration of the vitreous and anterior chamber, with one of these eyes demonstrating retinal necrosis.

Conclusions

Escalating doses of intravitreous adalimumab in rabbit eyes caused no detectable functional or structural ocular toxicity up to a dose of 0.50 mg. Administration of 1.0 mg in 0.1 ml was associated with an inflammatory reaction and retinal necrosis.
Literatur
1.
Zurück zum Zitat Theodossiadis PG, Markomichelakis NN, Sfikakis PP (2007) Tumor necrosis factor antagonists: preliminary evidence for an emerging approach in the treatment of ocular inflammation. Retina 27:399–413PubMedCrossRef Theodossiadis PG, Markomichelakis NN, Sfikakis PP (2007) Tumor necrosis factor antagonists: preliminary evidence for an emerging approach in the treatment of ocular inflammation. Retina 27:399–413PubMedCrossRef
2.
Zurück zum Zitat Sobrin L, Kim EC, Christen W, Papadaki T, Letko E, Foster CS (2007) Infliximab therapy for the treatment of refractory ocular inflammatory disease. Arch Ophthalmol 125:895–900PubMedCrossRef Sobrin L, Kim EC, Christen W, Papadaki T, Letko E, Foster CS (2007) Infliximab therapy for the treatment of refractory ocular inflammatory disease. Arch Ophthalmol 125:895–900PubMedCrossRef
3.
Zurück zum Zitat Murphy CC, Ayliffe WH, Booth A, Makanjuola D, Andrews PA, Jayne D (2004) Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis. Ophthalmology 111:352–356PubMedCrossRef Murphy CC, Ayliffe WH, Booth A, Makanjuola D, Andrews PA, Jayne D (2004) Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis. Ophthalmology 111:352–356PubMedCrossRef
4.
Zurück zum Zitat Kahn P, Weiss M, Imundo LF, Levy DM (2006) Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology 113:860–864PubMedCrossRef Kahn P, Weiss M, Imundo LF, Levy DM (2006) Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology 113:860–864PubMedCrossRef
5.
Zurück zum Zitat Saurenmann RK, Levin AV, Rose JB, Parker S, Rabinovitch T, Tyrrell PN, Feldman BM, Laxer RM, Schneider R, Silverman ED (2006) Tumour necrosis factor α inhibitors in the treatment of childhood uveitis. Rheumatology 45:982–989PubMedCrossRef Saurenmann RK, Levin AV, Rose JB, Parker S, Rabinovitch T, Tyrrell PN, Feldman BM, Laxer RM, Schneider R, Silverman ED (2006) Tumour necrosis factor α inhibitors in the treatment of childhood uveitis. Rheumatology 45:982–989PubMedCrossRef
6.
Zurück zum Zitat Markomichelakis NN, Theodossiadis PG, Pantelia E, Papaefthimiou S, Theodossiadis GP, Sfikakis PP (2004) Infliximab for chronic cystoid macular edema associated with uveitis. Am J Ophthalmol 138:648–650PubMedCrossRef Markomichelakis NN, Theodossiadis PG, Pantelia E, Papaefthimiou S, Theodossiadis GP, Sfikakis PP (2004) Infliximab for chronic cystoid macular edema associated with uveitis. Am J Ophthalmol 138:648–650PubMedCrossRef
7.
Zurück zum Zitat Manzano RPA, Carvounis PE, Albini TA, Holz ER (2007) Etanercept monotherapy induces complete resolution of cystoid macular edema in a patient with refractory intermediate uveitis. Retinal Cases and Brief Reports 1:261–263 Manzano RPA, Carvounis PE, Albini TA, Holz ER (2007) Etanercept monotherapy induces complete resolution of cystoid macular edema in a patient with refractory intermediate uveitis. Retinal Cases and Brief Reports 1:261–263
8.
Zurück zum Zitat Shi X, Semkova I, Muther PS, Dell S, Kociok N, Joussen AM (2006) Inhibition of TNF-alpha reduces laser-induced choroidal neovascularization. Exp Eye Res 83:1325–1334PubMedCrossRef Shi X, Semkova I, Muther PS, Dell S, Kociok N, Joussen AM (2006) Inhibition of TNF-alpha reduces laser-induced choroidal neovascularization. Exp Eye Res 83:1325–1334PubMedCrossRef
9.
Zurück zum Zitat Markomichelakis NN, Theodossiadis PG, Sfikakis PP (2005) Regression of neovascular age-related macular degeneration following infliximab therapy. Am J Ophthalmol 139:537–540.PubMedCrossRef Markomichelakis NN, Theodossiadis PG, Sfikakis PP (2005) Regression of neovascular age-related macular degeneration following infliximab therapy. Am J Ophthalmol 139:537–540.PubMedCrossRef
10.
Zurück zum Zitat Sebastian RT, Harding SP, Bucknall RC, Pearce IA (2006) Optimizing the use of tumor necrosis factoralpha inhibitors in refractory uveitis. Arch Ophthalmol 124:1505PubMedCrossRef Sebastian RT, Harding SP, Bucknall RC, Pearce IA (2006) Optimizing the use of tumor necrosis factoralpha inhibitors in refractory uveitis. Arch Ophthalmol 124:1505PubMedCrossRef
11.
Zurück zum Zitat Vazquez-Cobian LB, Flynn T, Lehman TJ (2006) Adalimumab therapy for childhood uveitis. J Pediatr 149:572–575PubMedCrossRef Vazquez-Cobian LB, Flynn T, Lehman TJ (2006) Adalimumab therapy for childhood uveitis. J Pediatr 149:572–575PubMedCrossRef
12.
Zurück zum Zitat Biester S, Deuter C, Michels H, Haefner R, Kuemmerle-Deschner J, Doycheva D et al (2007) Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol 91:319–324PubMedCrossRef Biester S, Deuter C, Michels H, Haefner R, Kuemmerle-Deschner J, Doycheva D et al (2007) Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol 91:319–324PubMedCrossRef
13.
Zurück zum Zitat Guignard S, Gossec L, Salliot C, Ruyssen-Witrand A, Luc M, Duclos M et al (2006) Efficacy of tumour necrosis factor blockers in reducing uveitis flares in patients with spondylarthropathy: a retrospective study. Ann Rheum Dis 65:1631–1634PubMedCrossRef Guignard S, Gossec L, Salliot C, Ruyssen-Witrand A, Luc M, Duclos M et al (2006) Efficacy of tumour necrosis factor blockers in reducing uveitis flares in patients with spondylarthropathy: a retrospective study. Ann Rheum Dis 65:1631–1634PubMedCrossRef
14.
Zurück zum Zitat Mushtaq B, Saeed T, Situnayake RD, Murray PI (2007) Adalimumab for sight-threatening uveitis in Behcet’s disease. Eye 21:824–825PubMedCrossRef Mushtaq B, Saeed T, Situnayake RD, Murray PI (2007) Adalimumab for sight-threatening uveitis in Behcet’s disease. Eye 21:824–825PubMedCrossRef
15.
Zurück zum Zitat Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295:2275–2285PubMedCrossRef Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295:2275–2285PubMedCrossRef
16.
Zurück zum Zitat Schiff MH, Burmester GR, Kent JD, Pangan AL, Kupper H, Fitzpatrick SB et al (2006) Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. Ann Rheum Dis 65:889–894PubMedCrossRef Schiff MH, Burmester GR, Kent JD, Pangan AL, Kupper H, Fitzpatrick SB et al (2006) Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis. Ann Rheum Dis 65:889–894PubMedCrossRef
17.
Zurück zum Zitat Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY et al (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431PubMedCrossRef Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY et al (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431PubMedCrossRef
18.
Zurück zum Zitat Bashshur ZF, Schakal A, Hamam RN, El Haibi CP, Jaafar RF, Noureddin BN (2007) Intravitreal Bevacizumab vs verteporfin photodynamic therapy for neovascular age related macular degeneration. Arch Ophthalmol 125:1357–1361PubMedCrossRef Bashshur ZF, Schakal A, Hamam RN, El Haibi CP, Jaafar RF, Noureddin BN (2007) Intravitreal Bevacizumab vs verteporfin photodynamic therapy for neovascular age related macular degeneration. Arch Ophthalmol 125:1357–1361PubMedCrossRef
19.
Zurück zum Zitat Fauser S, Kalbacher H, Alteheld N, Koizumi K, Krohne TU, Joussen AM (2004) Pharmacokinetics and safety of intravitreally delivered etanercept. Graefes Arch Clin Exp Ophthalmol 242:582–586PubMedCrossRef Fauser S, Kalbacher H, Alteheld N, Koizumi K, Krohne TU, Joussen AM (2004) Pharmacokinetics and safety of intravitreally delivered etanercept. Graefes Arch Clin Exp Ophthalmol 242:582–586PubMedCrossRef
20.
Zurück zum Zitat Kivilcim M, Peyman GA, Kazi AA, Dellacroce J, Ghobrial RN, Manzano R (2007) Intravitreal toxicity of high-dose etanercept. J Ocul Pharmacol Ther 23:57–62PubMedCrossRef Kivilcim M, Peyman GA, Kazi AA, Dellacroce J, Ghobrial RN, Manzano R (2007) Intravitreal toxicity of high-dose etanercept. J Ocul Pharmacol Ther 23:57–62PubMedCrossRef
21.
Zurück zum Zitat Tsilimbaris MK, Panagiotoglou TD, Charisis SK, Anastasakis A, Krikonis TS, Christodoulakis E (2007) The use of intravitrealetanercept in diabetic macular oedema. Semin Ophthalmol 22:75–79PubMedCrossRef Tsilimbaris MK, Panagiotoglou TD, Charisis SK, Anastasakis A, Krikonis TS, Christodoulakis E (2007) The use of intravitrealetanercept in diabetic macular oedema. Semin Ophthalmol 22:75–79PubMedCrossRef
22.
Zurück zum Zitat Galor A, Perez VL, Hammel JP, Lowder CY (2006) Differential effectiveness of etanercept and infliximab in the treatment of ocular inflammation. Ophthalmology 113:2317–2323PubMedCrossRef Galor A, Perez VL, Hammel JP, Lowder CY (2006) Differential effectiveness of etanercept and infliximab in the treatment of ocular inflammation. Ophthalmology 113:2317–2323PubMedCrossRef
23.
Zurück zum Zitat Manzano RPA, Peyman GA, Khan P, Kivilcim M (2006) Testing intravitreal toxicity of bevacizumab (Avastin). Retina 26(3): 257–261PubMedCrossRef Manzano RPA, Peyman GA, Khan P, Kivilcim M (2006) Testing intravitreal toxicity of bevacizumab (Avastin). Retina 26(3): 257–261PubMedCrossRef
Metadaten
Titel
Ocular toxicity of intravitreous adalimumab (Humira) in the rabbit
verfasst von
Roberta P. A. Manzano
Gholam A. Peyman
Petros E. Carvounis
Muhamet Kivilcim
Palwasha Khan
Patricia Chevez-Barrios
Walter Takahashi
Publikationsdatum
01.06.2008
Verlag
Springer-Verlag
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 6/2008
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-008-0765-z

Weitere Artikel der Ausgabe 6/2008

Graefe's Archive for Clinical and Experimental Ophthalmology 6/2008 Zur Ausgabe

Neu im Fachgebiet Augenheilkunde

Ophthalmika in der Schwangerschaft

Die Verwendung von Ophthalmika in der Schwangerschaft und Stillzeit stellt immer eine Off-label-Anwendung dar. Ein Einsatz von Arzneimitteln muss daher besonders sorgfältig auf sein Risiko-Nutzen-Verhältnis bewertet werden. In der vorliegenden …

Operative Therapie und Keimnachweis bei endogener Endophthalmitis

Vitrektomie Originalie

Die endogene Endophthalmitis ist eine hämatogen fortgeleitete, bakterielle oder fungale Infektion, die über choroidale oder retinale Gefäße in den Augapfel eingeschwemmt wird [ 1 – 3 ]. Von dort infiltrieren die Keime in die Netzhaut, den …

Bakterielle endogene Endophthalmitis

Vitrektomie Leitthema

Eine endogene Endophthalmitis stellt einen ophthalmologischen Notfall dar, der umgehender Diagnostik und Therapie bedarf. Es sollte mit geeigneten Methoden, wie beispielsweise dem Freiburger Endophthalmitis-Set, ein Keimnachweis erfolgen. Bei der …

So erreichen Sie eine bestmögliche Wundheilung der Kornea

Die bestmögliche Wundheilung der Kornea, insbesondere ohne die Ausbildung von lichtstreuenden Narben, ist oberstes Gebot, um einer dauerhaften Schädigung der Hornhaut frühzeitig entgegenzuwirken und die Funktion des Auges zu erhalten.   

Update Augenheilkunde

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.