Short-term real-world outcomes of diabetic macular edema treated with intravitreal faricimab

doi:10.21203/rs.3.rs-4364919/v1

Faricimab, a new drug for diabetic macular edema (DME), was made available in Japan in 2022. However, few reports have been published about its treatment outcomes in clinical practice. To assess the short-term outcomes of intravitreal faricimab (IVF) in patients with DME, the records of patients with DME receiving IVF therapy between July 2022 and July 2023 at Juntendo University Hospital were retrospectively reviewed. Their best-corrected visual acuities in the logarithm of the minimum angle of resolution units and central macular thicknesses were compared at baseline and one month after the final IVF. Eighteen patients and 22 eyes were included and allocated to the naïve and switched groups: 12 cases (15 eyes) and 6 cases (7 eyes), respectively. The best-corrected visual acuity improved for the naïve group, but no difference was observed for the switched group. In contrast, the central macular thickness improved for both the naïve and switched groups. IVF demonstrated good short-term outcomes for DME, suggesting that it is effective for DME in clinical practice.

Health sciences/Diseases/Eye diseases

Health sciences/Diseases/Eye diseases/Retinal diseases

faricimab

diabetic macular edema

diabetic retinopathy

diabetes mellites

Diabetic retinopathy (DR) is the most common microvascular complication in patients with diabetes.¹ Diabetic macular edema (DME), which is a component of DR, causes vision loss. Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are currently the most effective treatment for DME.² However, they have several limitations, including the need for repetitive injections and insufficient response in a subset of patients.

Faricimab (Roche/Genentech, Basel, Switzerland) was developed as a bispecific antibody to bind VEGF-A and Ang2.³ It was approved in Japan in March 2022 and its use began in May 2022. It has anti-Ang2 effects and is expected to be more effective for DME than previous treatments.⁴ It is also expected to be effective for cases of ineffectiveness or resistance to existing drugs such as ranibizumab and aflibercept.

This study aimed to determine the short-term efficacy of faricimab for the treatment of DME.

The clinical characteristics of the patients are summarized in Table 1. This study included naïve (15 eyes of 12 patients) and switched (seven eyes of six patients) cases. The mean follow-up duration was 6.3 ± 3.6 months. The number of intravitreal faricimab (IVFs) was 3.3 ± 1.9, 2.7 ± 1.3, and 4.2 ± 2.4 for the all cases and the naïve and switched groups, respectively. For the switched group, the number of previous anti-VEGF injections was 7.6 ± 9.2. Five aflibercept and two ranibizumab drugs were previously administered as anti-VEGF drugs before switching to faricimab. Two eyes in the naive group had a history of vitrectomy.

Table 1. Demographic all patients

	All case
	Naïve	Switch
Case (eye)	18 (23)
	12 (15)	6 (8)
male (female)	12 (6)
	9 (2)	3 (4)
The number of IVF	3.3 ± 1.9
	2.7 ± 1.3	4.2 ± 2.4
Past history of anti-VEGF
		7.6 ± 9.2
Avitreous case (eye)	2 (2)
	2 (2)	0
PRN (TAE)*	15 (7)
	11 (4)	4 (3)
Mean follow-up period (months)	6.3 ± 3.6
	5.1 ± 3.7	8.4 ± 1.7
PRN, pro re nata; TAE, treat and extend *The teatment regimen of IVF.

The change in the logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) is shown in Fig. 1. For all cases and the naïve group, the logMAR BCVA improved after IVF (Fig. 1B). In contrast, the logMAR BCVA at baseline and after IVF were not different for the switched group (Fig. 1C).

Changes in the central macular thickness (CMTs) are shown in Fig. 2. The CMT significantly improved after IVF from the baseline for both groups (Figs. 2A–C). Additionally, both groups succussed the macula thickness under 300 µm (Figs. 3A–C).

In the present study, DME treatment with IVF was assessed retrospectively. IVF improved CMT for both the naïve and switched groups, suggesting a reduction in the retinal fluid. Visual acuity improved for the naïve but not for the switched group. These suggest that IVF is more effective at improving retinal morphological changes in DME.

This was a retrospective study, and the methods of drug administration varied (PRN or TAE, with or without the administration period of IVF). Cases in which no induction phase was provided were included, and the reasons for this were recognized, including the financial burden of the patient and fear of injecting the drug into the eye. Cases for which the exact number of injections required was not administered were also included, suggesting that this study reflects the actual clinical real-world aspects of the study.

This drug, anti-Ang2, has a new effect and is expected to be more effective for DME than previous treatments.³ It is also expected to be effective for cases of ineffectiveness or resistance to existing drugs such as ranibizumab and aflibercept. In this study, naïve patients showed improvements in visual acuity and retinal thickness, suggesting good fluid control. In contrast, the switched case group showed improvement in retinal thickness but not in visual acuity.

The risk factors for poor visual improvement after DME treatment for the naïve group were older age and poor vision before treatment.⁵ Murakami et al. showed that visual acuity was significantly worse for patients with cystoid macular edema than for those with the serous retinal detachment or diffuse type.⁶ Moreover, a disrupted ELM or parafoveal thickening was significantly correlated with poor visual acuity of patients with diffuse DME. However, the switched group in this study showed no obvious abnormalities in the outer retinal layers on OCT. Some previous reports have shown the efficacy of IVF for the switched cases.^7–9 These differences in results may be attributed to the small sample in this study, given the trend toward improvement in this study. The pathomorphology and photoreceptor statuses at the fovea and retinal edema in the parafovea should be continually considered as prognostic factors for DME.

This study has several limitations. First, the sample was small. Second, the IVF treatment methods varied from case to case. Third, the follow-up was relatively short. We intend to continue this longitudinal study using additional cases.

In this real-world study, IVF showed good short-term outcomes for DME. IVF may be effective for treating DME in clinical practice.

This study included 18 patients with 23 consecutive eyes treated with intravitreal faricimab (IVF) for DME between July 2022 and July 2023. They were divided into the naïve (15 eyes of 12 patients) and switched (seven eyes of six patients) groups, and their medical records were retrospectively reviewed. For the switched cases, one eye from each patient was excluded because of concomitant age-related macular degeneration. Finally, 22 eyes from the 18 patients with DME treated with IVF were included in this study. The follow-up lasted from July 2022 to August 2023. This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Juntendo University (16–292). All patients signed informed consent forms before IVF, and it was administered when retinal exudative changes (intraretinal and subretinal fluids) were detected by OCT.

All patients underwent comprehensive ophthalmic examinations, including logMAR BCVA, fundus ophthalmoscopy, and spectral-domain OCT (SD-OCT; Carl Zeiss and Hidelberg). OCT analyzed the CMT. The baseline data obtained immediately before IVF administration and data from the last visit during the follow-up were compared. The statistical analyses were performed using Prism 10 software.

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Acknowledgments

This work was supported by grants from MEXT/JSPS KAKENHI (19K23851, 20K18395 and 23K15918 to T.H.).

Author contribution

T. Hirakata, and S.N. designed all experiments. T. Hirakata, F.H., Y.N., D.S., S.Y., Y.H., and S.N recruited and followed all of the patients. T. Hirakata and S.N. analyzed the data. T. Hirakata wrote the manuscript.

Conflict of interest

No conflicting relations.

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No competing interests reported.

Short-term real-world outcomes of diabetic macular edema treated with intravitreal faricimab

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