Posters

NICE guidelines for optimizing ocriplasmin efficacy

Poster Details

First Author: A.Tyagi UK

Co Author(s):                  

Abstract Details

Purpose:

The National Institute for Health and Care Excellence (NICE) has recommended ocriplasmin as a therapeutic option for Vitreomacular Traction (VMT) / Vitreomacular Adhesion (VMA) that is both clinically and cost effective for certain patients. This study describes the NICE subgroups defined by baseline ocular characteristics chosen for their expected impact on treatment responsiveness, and compares them to real-world application of the same subgroups in clinical practice.

Setting:

Two multicenter phase III clinical trials, comprising 89 sites in Europe and the USA, were performed.

Methods:

Two phase III clinical trials were conducted using ocriplasmin with the primary endpoint being VMA resolution at day 28. Secondary endpoints included total PVD, closure of MH at day 28, avoidance of vitrectomy, and changes in best-corrected visual acuity (BCVA). 652 eyes were treated with 464 receiving ocriplasmin and 188 receiving placebo. Anatomic data obtained from OCT imaging include width of macular hole (MH) at baseline, presence of epiretinal membrane (ERM), and width of vitreomacular adhesion at baseline. Subgroup analyses were performed on the primary efficacy endpoint (VMA resolution at day 28) in order to determine differences in treatment effects based on baseline demographic and ocular characteristics. Furthermore, select subgroup analyses were done for total PVD, FTMH closure, vitrectomy, and BCVA. Using univariate and multivariate logistic regression approaches to study the covariate effects on the efficacy endpoints, a retrospective analysis of the MIVI-TRUST clinical trial data identified patient subgroups that show differential responses to ocriplasmin versus placebo treatment.

Results:

Post hoc analysis showed that 2 main subgroups had a differential response to ocriplasmin treatment compared to placebo. The VMA resolution rate at day 28 showed a significant difference in both the VMA without ERM (29.8% vs 7.7%, p<0.001) and VMA with MH (50% vs 25.5%, p=0.006) subgroups. Consistent with the VMA resolution results, the VMA without ERM subgroup (17% vs 2.6%, p<0.001), and VMA with MH (22.6% vs 8.5%, p=0.033) showed significant differences to ocriplasmin treatment compared to placebo for total PVD. For the BCVA analysis, a greater percentage of ocriplasmin treated patients compared to placebo in the VMA with MH subgroup gained at least 10 letters (44.3% vs 30.4%, p=0.104, at month 6) and at least 15 letters (27.4% vs 13.0%, p=0.063). A higher proportion of patients with BCVA improvement was also seen in the VMA without ERM subgroup (25.5% vs 15.4%, p=0.051 gained 10 letters or more, and 10.1% vs 5.1%, p=0.14 gained 15 letters or more, for ocriplasmin vs placebo, respectively). While the BCVA responses favored ocriplasmin, the comparisons did not reach statistical significance. Importantly, real-world data being generated according to the NICE guidelines is being analyzed and will be presented.

Conclusions:

NICE recommended the use of ocriplasmin in patients with VMT/ VMA with severe symptoms or MH less than 400 μm, in the absence of ERM. For UK approval, NICE endorsed the subgroup approach for patient populations that are clinically heterogeneous. These subgroups have diagnostic relevance and can be identified with available technology in clinical practice. As positive predictors of ocriplasmin responsiveness, they highlight the necessity of patient selection. Real-world clinical experience is also essential for comparison to the clinical trial data that has defined these key factors for ocriplasmin responsiveness. FINANCIAL INTEREST: One of more of the authors... research is funded, fully or partially, by a company producing, developing or supplying the product or procedure presented