Abstract
Purpose :
Leber hereditary optic neuropathy (LHON) is a rare mitochondrial disease in which patients present with progressive, bilateral vision loss. Idebenone has been approved in Europe for the treatment of LHON. PAROS was a phase IV, post-authorization study (NCT02771379) with the primary objective to further evaluate the long-term safety profile of idebenone in the treatment of LHON patients in routine clinical care.
Methods :
PAROS was a multicenter, prospective, non-interventional safety study, conducted at 26 centers across 6 European countries. Adverse event (AE) reports were collected for the assessment of long-term idebenone safety in 224 LHON patients, stratified by prior idebenone treatment at baseline (naïve vs non-naïve). A Kaplan-Meier (KM) estimate of the proportion of patients with a related treatment-emergent AE (TEAE), and the number of patients who discontinued treatment due to a TEAE were determined from baseline.
Results :
The safety population comprised 185 idebenone non-naïve and 39 idebenone naïve patients. The mean (standard deviation) duration of treatment was 25.1 (14.2) months. A total of 130 (58.0%) patients experienced 382 TEAEs, and 50 (22.3%) patients experienced 82 adverse drug reactions. Related TEAEs occurred in a higher proportion of idebenone naïve patients from baseline to last visit (Table). Regardless of prior idebenone use, the proportion of additional patients with related TEAEs was highest in the first year after baseline, and plateaued from year 3, after which no new patients experienced a related TEAE. Overall, 34 (15.2%) patients discontinued treatment due to TEAEs, with a higher rate observed in idebenone naïve compared to non-naïve patients (25.6% vs 13.0%) (Figure). Regardless of prior idebenone treatment at baseline, the majority of AEs leading to discontinuation were mild.
Conclusions :
The safety profile reported here is similar to that observed in a previous open-label study (LEROS). Results from this long-term real world study therefore confirm that idebenone is well-tolerated in patients with LHON when used in routine clinical practise.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.