Enhancing patient outcomes

(Image credit: AdobeStock/neirfy)

In the pursuit of optimizing care for diabetic macular edema (DME), the PALADIN study (NCT02424019), a nonrandomized, open-label,
observational phase 4 trial spanning 36 months, sheds light on the real-world impact of the 0.19 mg fluocinolone acetonide (FAc; Iluvien) implant. It evaluated the 0.19-mg FAc implant in 202 eyes of 159 patients diagnosed with DME,¹ providing a nuanced understanding of how the Iluvien (Alimera Sciences) implant can potentially improve vision and reduce treatment burden.

The PALADIN study observed improvement in best-corrected visual acuity (BCVA) following the administration of the 0.19 mg FAc implant. Over the 36 months post FAc, there was a statistically significant mean improvement of 4.5 letters compared to baseline (P = .0253). This contrasts with the 6.4-letter decline in visual acuity recorded during the preceding 36 months,² suggesting that the FAc implant may play a beneficial role in enhancing vision, likely by addressing the known undertreatment with anti-VEGF injections seen in real-world practice. Randomized clinical trials have shown a positive correlation between the number of anti-VEGF injections and visual gains. However, in real-world observational studies, patients received fewer injections, correlating with notably smaller visual improvements.³ Indeed, during the 36 months before the implant in this study, 75% of eyes received 5 or fewer yearly treatments.

The study highlights the treatment burden associated with DME by examining the frequency of interventions. In the 36 months leading up to FAc treatment, the eyes received a mean of 3.5 yearly treatments. With the introduction of the FAc implant, there was a notable reduction in the mean number of yearly supplemental treatments to 1.7 (P < .001). Additionally, 68% of eyes required 2 or fewer supplementary interventions annually post FAc, and at the end of the 36-month study, 25% of the eyes remained completely free of any additional treatment.⁴ This decline in treatment frequency indicates a potential reduction in the overall treatment burden for DME patients over a 3-year period.

Eyes that received supplemental treatments post FAc exhibited a higher incidence of intraocular pressure (IOP)–related events, underscoring the importance of continual monitoring and management of IOP. It is reassuring that the IOP events in PALADIN were similar to other postapproval studies and numerically lower than in the phase 3 FAME study (NCT01304706), likely due to the prior steroid challenge that is required by the label.¹

The findings from the PALADIN study have guided the design of the NEW DAY study (NCT04469595). In this phase 4, prospective clinical trial, treatment-naive eyes with DME are randomly assigned either to aflibercept or Iluvien plus aflibercept as needed. The 18-month NEW DAY results are anticipated in early 2025.

The measured improvement in vision and the reduction in treatment burden are noteworthy findings. While the findings are promising, maintaining a balanced view and addressing associated considerations such as IOP-related events are paramount. Integrating these insights into clinical practice may pave the way for a more nuanced and patient-centric treatment approach, where Iluvien can play a strategic role in improving outcomes and reducing the overall burden of care.

References

1. Singer MA, Sheth V, Mansour SE, Coughlin B, Gonzalez VH. Three-year safety and efficacy of the 0.19-mg fluocinolone acetonide intravitreal implant for diabetic macular edema: the PALADIN study. Ophthalmology. 2022;129(6):605-613. doi:10.1016/j.ophtha.2022.01.015

2. Merrill PT, Holekamp N, Roth D, Kasper J, Grigorian R; PALADIN Study Group. The 0.19-mg fluocinolone acetonide intravitreal implant reduces treatment burden in diabetic macular edema. Am J Ophthalmol. 2023;248:16-23. doi:10.1016/j.ajo.2022.09.017

3. Bailey C, et al. Poster presented at: 8th World Congress on Controversies in Ophthalmology (COPHy); March 30-April 1, 2017; Madrid, Spain.

4. Merrill PT, Cutino A, et al. 0.19 mg fluocinolone acetonide implant improves vision and treatment burden in patients with diabetic macular edema: the PALADIN study. Presented at: American Academy of Ophthalmology Annual Meeting; November 5, 2023; San Francisco, CA.