By Lucy Piper, Senior medwireNews Reporter
Placebo-controlled trial findings show that lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibition modestly benefits the vision of patients with centre-involved diabetic macular oedema (DME) and warrants further investigation.
The action of Lp-PLA2 generates products from oxidized phospholipids that are potent mediators of retinal and cerebral vascular permeability associated with DME, therefore their inhibition with selective inhibitors is thought to be a potential mechanism for reducing oedema.
Giovanni Staurenghi (University of Milan, Italy) and team investigated the potential of one such selective inhibitor, darapladib, in a phase IIa study. They randomly assigned 36 patients with a baseline vision of 20/32 to 20/320 to receive 160 mg of the drug once daily for 3 months and 18 to receive placebo.
At 3 months, patients receiving darapladib achieved a significant 4.06 Early Treatment Diabetic Retinopathy Study (ETDRS) letters improvement in best-corrected visual acuity (BCVA) and a significant 57 µm reduction in central subfield thickness from baseline.
By contrast, neither the mean 1.67 ETDRS letters improvement in BCVA nor the 34 µm decrease in central subfield thickness achieved by placebo-treated patients at 3 months were significant.
To account for a ceiling effect for improvement in vision, the researchers also conducted a post-hoc analysis of a subset of patients with poorer vision at baseline of 20/40 to 20/320. For this group, the average improvement in BCVA for patients taking darapladib was 5.17 ETDRS letters and the average decrease in central subfield thickness was 53 µm, both of which were significant compared with baseline.
For placebo-treated patients with poorer vision, the mean increase of 0.61 ETDRS letters and 16 µm decrease in central subfield thickness were not significant.
The researchers also report in Ophthalmology that the proportion of patients achieving driving vision, of 20/40 or better, increased over the 3-month period among those given darapladib, by an average 18%, whereas it declined by 7% among patients given placebo.
Darapladib was a well-tolerated treatment with no severe ocular or drug-related adverse events reported and comparable ocular and nonocular adverse events to those with placebo.
Staurenghi and colleagues say that the results for darapladib are “intermediate” to those seen with laser and ranibizumab treatment. They believe Lp-PLA2 to be “a novel mechanism for potential treatment of diabetic eye disease”, adding that it “seems to be distinct from that of other anti-[vascular endothelial growth factor] standard of care.”
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