OR WAIT null SECS
Results from the real-world AUSSIEDEX study suggest dexamethasone implant significantly improved anatomic outcomes at 52 weeks and showed no new safety concerns.
Dexamethasone intravitreal implant 0.7 mg monotherapy significantly improved anatomic outcomes at 52 weeks without new safety concerns in patients with anti-vascular endothelial growth factor (VEGF) refractory diabetic macular edema (DME), according to new research.1
Data from the AUSSIEDEX study showed dexamethasone monotherapy did not have a statistically significant effect on best-corrected visual acuity (BCVA) at week 52 in early versus late-switch patients; however, early-switch patients had, on average, better BCVA than late-switch patients at 52 weeks.
“Our findings thus indicate that dexamethasone implant monotherapy is an effective treatment option for patients with anti-VEGF-refractory DME, regardless of the timing of the switch from anti-VEGF agents to dexamethasone implant,” wrote the investigative team, led by Professor Paul Mitchell, Clinical Ophthalmology & Eye Health, Westmead Clinical School, University of Sydney.
Intravitreal corticosteroids, including the dexamethasone intravitreal implant 0.7mg, can inhibit the synthesis of VEGF and other pro-inflammatory mediators that cause DME. With broader anti-inflammatory effects compared to anti-VEGF, corticosteroids may be able to treat a greater range of patients. The largest prospective, real-world study, AUSSIEDEX was designed to assess dexamethasone implant’s effectiveness and safety as a treatment for treatment-naive or anti-VEGF refractory DME in 25 Australian clinics.
Previously published, primary results from AUSSIEDEX indicate dexamethasone implant monotherapy significantly improved central subfield retinal thickness (CRT) and BCVA at 52 weeks in treatment-naive eyes, without new safety concerns.2 Here, the analysis reported outcomes in anti-VEGF non-responders; non-response was defined as a failure to achieve a ≥5-letter BCVA gain and/or clinically significant CRT reduction after 3–6 anti-VEGF injections for DME.
After an initial baseline visit, reinjection was permitted at ≥16-week intervals. The mean number of dexamethasone injections per eye to week 52 was recorded, as were the changes in mean BCVA and CRT from baseline. Post-hoc analyses of the effectiveness variables were performed in non-responder subsets who switched to dexamethasone implants early (after 3–6 anti-VEGF injections) or late (after >6 anti-VEGF injections).
Of 200 patients enrolled in AUSSIEDEX, 143 (71.5%) were non-responders to anti-VEGF therapy and 113 (79.0%) completed the study. The mean number of dexamethasone injections over 52 weeks was 2.3 (95% CI, 2.2 - 2.5). Among non-responders who received >1 injection, the mean interval was 148.6 days.
Upon analysis, the change in mean BCVA from baseline was statistically significant at weeks 6, 16, and 24, but not at week 52, for the primary endpoint. More than 72% of patients reported a BCVA gain or no change from baseline at weeks 6, 16, 24, and 52. The analysis showed 37.4% of patients gained ≥5 letters, 35.3% had unchanged BCVA, and 27.3% lost ≥5 letters at week 52.
The analysis showed the mean CRT improved significantly from a baseline of 417.8 µm at week 52. The change in mean CRT from baseline was statistically significant at weeks 6, 16, 24, and 52 showing reductions of 99.2, 32.7, 62.9, and 60.9 µm, respectively (P <.001).
Of the 143 eyes noted as anti-VEGF non-responders, 53 (37.1%) and 89 (62.2%) were early-switch and late-switch patients, respectively; a single patient (0.7%) had missing information on switching. Consistent with results in overall non-responders, the change in mean BCVA from baseline was not statistically significant at week 52 in either subset.
Although the early-late switch difference in BCVA was not statistically significant (P ≥.056) at baseline, week 6, week 16, and week 24, the difference was statistically significant at week 52 (9.41; 95% CI, 1.85 - 16.96; P = .015). As early-switch patients had greater BCVA improvement than late-switch patients, investigators suggested earlier DME treatment with dexamethasone is a factor that could improve functional outcomes.
“Randomized studies in which patients would be switched from anti-VEGF therapy to dexamethasone implant early vs later (based on BCVA and CRT, as in the current study, and/or additional parameters such as hyperreflective retinal foci and neurosensory detachment) are warranted to verify these findings in controlled settings,” investigators wrote.