دورية أكاديمية
Indirect comparison of lenadogene nolparvovec gene therapy versus natural history in patients with Leber hereditary optic neuropathy carrying the m.11778G>A MT-ND4 mutation
| العنوان: | Indirect comparison of lenadogene nolparvovec gene therapy versus natural history in patients with Leber hereditary optic neuropathy carrying the m.11778G>A MT-ND4 mutation |
|---|---|
| المؤلفون: | Carelli, V, Newman, NJ, Yu-Wai-Man, P, Biousse, V, Moster, ML, Subramanian, PS, Vignal-Clermont, C, Wang, AG, Donahue, SP, Leroy, Bart, Sergott, RC, Klopstock, T, Sadun, AA, Rebolleda Fernández, G, Chwalisz, BK, Banik, R, Girmens, JF, La Morgia, C, DeBusk, AA, Jurkute, N, Priglinger, C, Karanjia, R, Josse, C, Salzmann, J, Montestruc, F, Roux, M, Taiel, M, Sahel, JA, the LHON Study, Group |
| المصدر: | OPHTHALMOLOGY AND THERAPY ; ISSN: 2193-8245 ; ISSN: 2193-6528 |
| سنة النشر: | 2023 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Medicine and Health Sciences, Visual acuity, Natural history, MT-ND4, LHON, Leber hereditary optic neuropathy, Gene therapy |
| الوصف: | Introduction Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G > A ND4 mutation (MT-ND4). A previous pooled analysis of phase 3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase 3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174.Methods The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase 3 studies (REVERSE, RESCUE and their long-term extension trial RESTORE; and REFLECT trial) was compared to the spontaneous evolution of an external control group of 208 matched patients from 11 natural history studies.Results Treated patients showed a clinically relevant and sustained improvement in their visual acuity when compared to natural history. Mean improvement versus natural history was - 0.30 logMAR (+ 15 ETDRS letters equivalent) at last observation (P < 0.01) with a maximal follow-up of 3.9 years after injection. Most treated eyes were on-chart as compared to less than half of natural history eyes at 48 months after vision loss (89.6% versus 48.1%; P < 0.01) and at last observation (76.1% versus 44.4%; P < 0.01). When we adjusted for covariates of interest (gender, age of onset, ethnicity, and duration of follow-up), the estimated mean gain was - 0.43 logMAR (+ 21.5 ETDRS letters equivalent) versus natural history at last observation (P < 0.0001). Treatment effect was consistent across all phase 3 clinical trials. Analyses from REFLECT suggest a larger treatment effect in patients receiving bilateral injection compared to unilateral injection.Conclusion The efficacy of lenadogene nolparvovec in improving visual acuity in MT-ND4 LHON was confirmed in a large cohort of patients, compared to the spontaneous natural history decline. Bilateral ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://biblio.ugent.be/publication/01GQJ1SPSXTA8KWP5XWE98B4YXTest; http://hdl.handle.net/1854/LU-01GQJ1SPSXTA8KWP5XWE98B4YXTest; http://dx.doi.org/10.1007/s40123-022-00611-xTest; https://biblio.ugent.be/publication/01GQJ1SPSXTA8KWP5XWE98B4YX/file/01GQJ1XTVN3AF30Z5WA8FS39Y7Test |
| DOI: | 10.1007/s40123-022-00611-x |
| الإتاحة: | https://doi.org/10.1007/s40123-022-00611-xTest https://biblio.ugent.be/publication/01GQJ1SPSXTA8KWP5XWE98B4YXTest http://hdl.handle.net/1854/LU-01GQJ1SPSXTA8KWP5XWE98B4YXTest https://biblio.ugent.be/publication/01GQJ1SPSXTA8KWP5XWE98B4YX/file/01GQJ1XTVN3AF30Z5WA8FS39Y7Test |
| حقوق: | Creative Commons Attribution-NonCommercial 4.0 International Public License (CC BY-NC 4.0) ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.9CF547E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s40123-022-00611-x |
|---|