Assessing the impact of long‐term idebenone treatment on various visual acuity outcomes in Leber's hereditary optic neuropathy (LHON): Results, according to disease stage, from the prospective, natural history‐controlled LEROS study

Abstract

AbstractPurpose: For patients with LHON, preservation of functional visual acuity (VA) and/or recovery of lost VA are desirable outcomes. Beyond this, prevention of further VA worsening is also important. In LEROS, VA outcomes following 24 months of idebenone treatment were compared to an external, matched, natural history (NH) cohort. Here, we report results from a cumulative frequency analysis to understand the impact of idebenone across the range of possible VA outcomes.Methods: Patients with LHON onset ≤5 years prior were enrolled and stratified by time since onset: subacute/dynamic (≤1 year) and chronic (>1 year). Data from 181 patients treated up to 24 months were compared to retrospective data from an external natural history (NH) cohort (372 patients), matched by time since onset. In a cumulative frequency analysis, VA change was assessed from baseline to month 24. A change of ≥0.2 logMAR was considered a clinically relevant recovery or worsening, depending on the direction of change.Results: In subacute/dynamic eyes treated with idebenone for 24 months, 47.9% (58/121) experienced a recovery of VA, and 25.8% (24/93) experienced VA worsening. This compared to 33.3% (25/75), and 51.0% (25/49) of untreated subacute/dynamic eyes displaying a recovery or worsening, respectively. In chronic eyes, recovery was observed in 31.9% (37/116) that had undergone treatment versus 16.1% (15/93) when untreated. A VA worsening was observed for 2.9% (2/68) of treated chronic eyes versus 20.0% (12/60) of untreated. The majority of treatment emergent adverse events were considered of mild to moderate intensity, with only 11.3% considered to be related to idebenone treatment.Conclusions: In both the subacute/dynamic and chronic stages of LHON, idebenone treatment was able to boost VA recovery and prevent further VA deterioration. Consistent with previous findings, idebenone was well tolerated with no new safety concerns observed.