LHON is a mitochondrial disease causing progressive, bilateral central vision loss. Potential triggers include tobacco or heavy alcohol use and vitamin B12 deficiency. Idebenone is approved for treatment of patients with LHON in Europe.

PAROS (NCT02771379) was a phase IV, non-interventional, post-authorization safety study conducted at 26 centers in 6 European countries. Adverse event (AE) reports were prospectively collected. Treatment-emergent (TE)AEs, serious TEAEs, drug-related TEAEs, TEAEs of special interest (TEAESIs), and idebenone discontinuations due to TEAEs, including lack or loss of effect, were collected. This analysis includes subpopulations of LHON patients with a medical history of alcohol/tobacco use/abuse (Alc/Tob) or vitamin B12 deficiency (VitB12) reported at baseline.

A total of 224 enrolled patients received treatment with idebenone and were included in the overall safety population. Median (Q1, Q3) treatment duration was 22.4 (13.6, 37.4) months. The majority of patients were idebenone non-naïve at baseline (Alc/Tob: 87.2% [n=34/39]; VitB12: 95.8% [n=23/24]). A greater proportion of VitB12 patients experienced a TEAE (75.0% [n=18/24]) versus Alc/Tob patients (59.0% [n=23/39]) and the overall population (58.0% [n=130/224]). The proportion experiencing drug-related TEAEs was similar overall and across subpopulations (range 22.3–25.6%); none were deemed serious for the subpopulations. Overall, 15.2% (n=34/224) of patients discontinued idebenone due to a TEAE (Alc/Tob: 23.1% [n=9/39]; VitB12: 8.3% [n=2/24]), most frequently due to lack or loss of idebenone effect (overall: n=26/34; Alc/Tob: n=7/9; VitB12: n=2/2). TEAESIs occurred in 11 Alc/Tob and six VitB12 patients.  

Long-term idebenone treatment was well-tolerated overall and in the Alc/Tob and VitB12 subpopulations, with no unexpected safety findings observed in a real-world clinical setting. Results were consistent with the known safety profile of idebenone.