RSS-Feed abonnieren
DOI: 10.1055/a-1274-3675
Real Life Data on Efficacy and Safety of Topical NGF Eye Drops (Cenegermin)
Artikel in mehreren Sprachen: English | deutsch![](https://www.thieme-connect.de/media/klimo/202012/lookinside/thumbnails/10-1055-a-1274-3675_kl2264_en-1.jpg)
Abstract
Background Topical NGF eye drops (Cenegermin) were approved in 2015 as an orphan drug for the treatment of neurotrophic keratopathy (NK). The active substance Cenegermin is a recombinant form of human NGF (nerve growth factor).
Objectives Presentation of efficacy and safety of Cenegermin for use in patients in an university real-life setting.
Material and Methods Retrospective study at the Köln University Eye Hospital from 2017 to 2019 with n = 11 eyes. Average follow-up was 13.5 ± 7.1 months. Reasons for treatment were neurotrophic keratopathy stage II and III, clinically mostly in combination with corneal neovascularization.
Results Seven eyes with a NK II and 4 eyes with a NK III with a median observation period of 13.6 months (range 1.2 – 20.3 months) from a total of 11 patients were included. The median patient age was 42.8 ± 23.6 years (range 18 – 75 years). Before the start of therapy, the median erosion area measured 3.1 ± 1.4 × 1.9 ± 1.1 mm and the median ulcer area had a size of 2.3 ± 1.1 × 2.1 ± 0.8 mm. After the start of therapy with Cenegermin (application 6×/day), the epithelial defect closed in all 11 study eyes (100%) within 4 – 12 weeks (mean: 49 d ± 9 d). In 9 out of 10 patients (90%) pre-existing corneal neovascularization regressed significantly (p < 0.001). Before the start of therapy, a value in the Luneau test of 2.9 ± 1.9 (minimum 1/6, maximum 4/6) was found and rose to a median value of 4.2 ± 1.7 (minimum 2/6, maximum 6/6) after 18 months (p = 0.015). Therapy with Cenegermin had no long-term effect on intraocular pressure: the pressure ranged between 13.2 ± 4.1 mmHg (minimum 8 mmHg, maximum 21 mmHg). Under therapy with NGF eye drops, 67% of the patients, after an initial decrease, showed a long-term improvement in visual acuity (BSCVA) from 0.72 ± 0.31 to 0.46 ± 0.29 logMAR after 18 months (p = 0.005). Relapses in form of a corneal erosion in the long-term follow-up were observed in only one eye. One patient had to stop therapy because of local pain, no other local and systemic side effects were observed.
Conclusion This real-life series on the use of Cenegermin in a university context shows a good effectiveness of the substance for epithelial closure in various underlying diseases (100% within 12 weeks). There is a long-term improvement in vision and corneal sensitivity. Larger real-life cohorts with various underlying diseases should follow.
Publikationsverlauf
Eingereicht: 01. September 2020
Angenommen: 27. September 2020
Artikel online veröffentlicht:
07. Dezember 2020
© 2020. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References/Literatur
- 1 Dompé Farmaceutici S.p.A. Oxervate prescribing information. Accessed August 1, 2018 at: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm618047.htm
- 2 Dompé Farmaceutici S.p.A. Evaluation of safety and efficacy of rhNGF in patients with stage 2 and 3 neurotrophic keratitis (REPARO) [NCT01756456]. Accessed July 29, 2019 at: https://clinicaltrials.gov/ct2/show/NCT01756456
- 3 Bucher F, Hos D, Matthaei M. et al. Corneal nerve alterations after Descemet membrane endothelial keratoplasty: an in vivo confocal microscopy study. Cornea 2014; 33: 1134-1139 doi:10.1097/ICO.0000000000000250
- 4 Bremond-Gignac D, Daruich A, Robert MP. et al. Recent innovations with drugs in clinical trials for neutrotrophic keratitis and refractory corneal ulcers. Expert Opin Investig Drugs 2019; 28: 1013-1020 doi:10.1080/13543784.2019.1677605
- 5 Sheha H, Tighe S, Hashem O. et al. Update on Cenegermin eye drops in the treatment of neurotrophic keratitis. Clin Ophthalmol 2019; 13: 1973-1980 doi:10.2147/OPTH.S185184
- 6 Adler J, Mertsch S, Menzel-Severing J. et al. Aktuelle und experimentelle Therapieansätze bei neutrotropher Keratopathie. Ophthalmologe 2019; 116: 127-137 doi:10.1007/s00347-018-0843-5
- 7 Cursiefen C, Seitz B, Kruse FE. Neurotrophic keratitis. Ophthalmologe 2005; 102: 7-14 doi:10.1007/s00347-004-1140-z
- 8 Dua HS, Said DG, Messmer EM. et al. Neurotrophic keratopathy. Prog Retin Eye Res 2018; 66: 107-131 doi:10.1016/j.preteyeres.2018.04.003
- 9 Seitz B, Grüterich M, Cursiefen C. et al. [Conservative and surgical treatment of neurotrophic keratopathy]. Ophthalmologe 2005; 102: 15-26 doi:10.1007/s00347-004-1161-7
- 10 European Medicine Agency. EMA/330858/2017 EMEA/H/C/004209. Oxervate. Accessed November 10, 2020 at: https://www.ema.europa.eu/en/documents/overview/oxervate-epar-summary-public_de.pdf
- 11 Pflugfelder SC, Massaro-Giordano M, Perez VL. et al. Topical recombinant human nerve growth factor (Cenegermin) for neutrotrophic keratopathy. Ophthalmology 2020; 127: 14-26 doi:10.1016/j.ophtha.2019.08.020
- 12 Fleeman N, Mahon J, Nevitt S. et al. Cenegermin for treating neutrophic keratitis: An evidence review group perspective of a NICE single technology appraisal. Pharmacoecon Open 2019; 3: 453-461 doi:10.1007/s41669-019-0138-z
- 13 Cursiefen C, Bock F, Horn FK. et al. GS-101 antisense oligonucleotide eye drops inhibit corneal neovascularization. Ophthalmology 2009; 116: 1630-1637 doi:10.1016/j.ophtha.2009.04.016
- 14 Dietrich T, Weisbach V, Seitz B. et al. [Manufacture of autologous serum eye drops for out-patient therapy: cooperation between ophthalmic clinic and transfusion medicine department]. Ophthalmologe 2008; 105: 1036-1038 1040–1042 doi:10.1007/s00347-008-1692-4
- 15 Tahmaz V, Gehlsen U, Sauerbier L. et al. Treatment of severe chronic ocular graft-versus-host disease using 100 % autologous serum eye drops from a sealed manufacturing system: a retrospective cohort study. Br J Ophthalmol 2017; 101: 322-326 doi:10.1136/bjophthalmol-2015-307666
- 16 Bonini S, Lambiase A, Rama P. et al. Phase I trial of recombinant human nerve growth factor for neurotrophic keratitis. Ophthalmology 2018; 125: 1468-1471 doi:10.1016/j.ophtha.2018.03.004
- 17 Bonini S, Lambiase A, Rama P. et al. Phase II randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis. Ophthalmology 2018; 125: 1332-1343 doi:10.1016/j.ophtha.2018.02.022
- 18 Deecks ED, Lamb YN. Cenegermin: a review in neutrotrophic keratitis. Drugs 2020; 80: 489-494 doi:10.1007/s40265-020-01289-w
- 19 Weinlander E, Ling J, Reddy A. et al. Epithelial plaque formation secondary to recombinant human nerve growth factor. Cornea 2020; 39: 1174-1176 doi:10.1097/ICO.0000000000002300