Long‐term efficacy of idebenone in patients with Leber hereditary optic neuropathy in the LEROS study: Analysing change in visual acuity over time according to age at symptom onset

Abstract

Aims/Purpose: Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to progressive, bilateral vision loss. Childhood‐onset LHON has a relatively good prognosis, suggesting that age at onset influences disease progression and potential response to treatment. In LEROS, a Phase IV, open‐label interventional study (ClinicalTrials.gov NCT02774005), visual acuity (VA) outcomes following 24 months of idebenone treatment (IDE) were compared to those of a Natural History (NH) cohort.Methods: LEROS included patients aged ≥12 years with a disease onset ≤5 years prior. Data from 181 patients were compared to retrospective data from a NH cohort (N = 372), matched by time since symptom onset. Here, we compare the difference in least squares‐mean VA change, or delta VA, from baseline to Month 24 in treated eyes versus those in the NH cohort (a negative value favours IDE). Eyes were stratified by time since symptom onset at baseline: subacute/dynamic (≤1 year) and chronic (>1 year) phase, and by age at symptom onset (<18 years, ≥18 years).Results: In treated subacute/dynamic eyes from the <18 years group (n = 22 IDE), delta VA was +0.38 logMAR (p = 0.020) relative to the NH cohort (n = 22). In the chronic phase, delta VA was −0.08 logMAR (n = 16 IDE vs n = 37 NH eyes; p = 0.405). In subacute/dynamic eyes from the ≥18 years group, delta VA was −0.18 logMAR (n = 99 IDE vs n = 53 NH; p = 0.060). In the chronic phase, delta VA was −0.21 logMAR (n = 100 IDE vs n = 56 NH; p < 0.001).Conclusions: In eyes of patients ≥18 years at symptom onset, VA improvement at Month 24 was greater in idebenone‐treated versus untreated NH eyes. Treatment benefit was particularly apparent in the chronic phase, corresponding to >10 additional letters on the ETDRS chart. In subacute/dynamic eyes, spontaneous VA recovery was unexpectedly high in the NH cohort. In chronic eyes from patients <18 years, a non‐significant trend favouring idebenone was observed.