Real-World Data Confirm Safety of Switching Between Ranibizumab Biosimilars

DME is a complication of diabetic retinopathy (DR) caused by fluid leakage from damaged retinal blood vessels, leading to swelling in the macula. | Image credit: Orawan - stock.adobe.com

Switching between ranibizumab biosimilars is safe and effective for patients receiving treatment for retinal conditions, with no reported immunogenicity issues or significant adverse events, according to early real-world data coming out of India.¹

The interventional retrospective, uncontrolled multicenter study represents early insight into the real-world effects of biosimilar-to-biosimilar switching among biosimilars administered intravitreally. Most switching studies compare the safety and efficacy of a biosimilar with its originator, and studies on ranibizumab products are typically conducted in wet age-related macular degeneration (AMD) populations, leaving out patients with retinal vein occlusion (RVO), DME, and myopic or secondary macular neovascularization (MNV).^2,3

DME is a complication of diabetic retinopathy (DR) caused by fluid leakage from damaged retinal blood vessels, leading to swelling in the macula.⁴ It can occur at any stage of DR and affects 3.8% of US adults aged 40 and older with diabetes.

The risk of DME is influenced by diabetes duration and poor glycemic control, making annual dilated eye exams essential for early detection. Treatments include focal laser photocoagulation for non–center-involved DME, which reduces vision loss risk by 50% to 70%, and intravitreal anti-vascular endothelial growth factor (VEGF) injections (e.g., aflibercept, bevacizumab, ranibizumab) for center-involved DME, which have been considered the standard of care since the early 2000s.

“To our knowledge, no switching trial has evaluated using biosimilars for retinal diseases other than our report of switching from the reference ranibizumab to the first biosimilar ranibizumab,” the authors noted.¹

Data on patients with DME, wet AMD, RVO, or MNV previously treated with a ranibizumab biosimilar were collected from 7 eye care centers in India for this interventional retrospective uncontrolled multicenter study. Data were collected anonymously from patients who received at least 1 intravitreal injection of ranibizumab biosimilar Ranieyes (0.5 mg) between July 2022 and July 2023, with a minimum follow-up of 4 weeks.

Off-label use was noted in cases of proliferative diabetic retinopathy, cystoid macular edema related to retinitis pigmentosa, and post-cataract surgery. Patients with other structural eye pathologies or vitreoretinal interface disorders were excluded.

Assessments included visual acuity using a Snellen chart (converted to logMAR), central subfield thickness (CST) via spectral-domain optical coherence tomography (OCT), intraocular pressure measurement, and a full ophthalmic examination. Efficacy was analyzed based on best-corrected visual acuity (BCVA) and CST at baseline and final follow-up.

During the study period, 474 Ranieyes injections were administered in 268 eyes of 254 patients, with a mean follow-up of 7.7 weeks. The primary indications included DME (n = 112) MNV (n = 92). Approximately half of the patients received a single injection. Among pretreated eyes, prior therapies included anti-VEGF agents (bevacizumab, ranibizumab, or aflibercept) and/or intravitreal steroids (triamcinolone or dexamethasone implants), with a median of 3 prior injections (range, 1-6).

Visual acuity improved significantly overall (P < .001) and within the DME (P < .001), MNV (P < .001), and RVO (P < .001) groups. Secondary MNV cases showed a significant visual acuity improvement from a baseline logMAR of 0.83 ± 0.26 (n = 6/45) to 0.45 ± 0.23 (n = 6/15) at last follow-up (P = .04). In PDR cases with vitreous hemorrhage, mean logMAR BCVA improved from 0.71 ± 0.54 (n = 6/30) to 0.28 ± 0.37 (n = 6/12), though this was not statistically significant (P = .13).

CST also significantly improved overall (P < .001) and within the DME (P < .001), MNV (P < .001), and RVO (P < .001) groups. However, in PDR cases, CST decreased from 341.6 ± 183.7 µm to 229.5 ± 25.3 µm (P = .16), and in CME cases, CST reduced from 325.5 ± 50.9 µm to 251 ± 65 µm (P = .12), with neither change reaching statistical significance. Both treatment-naïve and pretreated patients demonstrated significant improvements in visual acuity and CST.

Regarding safety, no drug-related ocular or systemic adverse events, including inflammation, vasculitis, or vision loss, were reported across study sites. While procedure-related events such as conjunctival hemorrhage, pain, and foreign-body sensation were noted, they were comparable with those observed with other anti-VEGF injections.

The study's limitations include the small sample size and the retrospective nature, which prevented the identification of injection procedure-related adverse events.

References

1. Biosimilar ranibizumab (Ranieyes) safety and efficacy in the real world: BRESER study. J Vitreoretin Dis. Published online February 27, 2025. doi:10.1177/24741264251322213

2. Ferreri D. No IBD activity changes following switch from biosimilar to originator infliximab. The Center for Biosimilars^®. March 3, 2025. Accessed March 18, 2025. https://www.centerforbiosimilars.com/view/no-ibd-activity-changes-following-switch-from-biosimilar-to-originator-infliximab

3. Petrullo J. Phase 3 study demonstrates comparable safety, efficacy between ranibizumab biosimilar, Lucentis for nAMD. The Center for Biosimilars. March 10, 2024. Accessed March 18, 2025. https://www.centerforbiosimilars.com/view/phase-3-study-demonstrates-comparable-safety-efficacy-between-ranibizumab-biosimilar-lucentis-for-namd

4. Lundeen EA, Andes LJ, Rein DB, et al. Trends in prevalence and treatment of diabetic macular edema and vision-threatening diabetic retinopathy among Medicare Part B fee-for-service beneficiaries. JAMA Ophthalmol. 2022;140(4):345-353. doi:10.1001/jamaophthalmol.2022.0052