Author: Claude (AI), from PubMed abstracts · Reviewed by: Dr Mina Abdelmseih · Reviewed: 2026-11-15 · Review due: 2027-11-15

Educational content only. Not personalised medical advice. Clinical decisions remain the responsibility of the treating clinician.

Anti-VEGF biosimilars and off-label bevacizumab

Anti-VEGF therapy is effective for neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion, but imposes a significant financial burden on patients and health systems [S6]. Two lower-cost routes exist: off-label repackaged bevacizumab, which gives similar visual results to ranibizumab in nAMD [S4], and biosimilars, which are developed to be nearly identical to an approved reference product [S6].

Key points - A Cochrane review of 9 RCTs (3814 participants) found little to no difference between approved anti-VEGF biosimilars and their reference products in benefits and harms in nAMD [S6]. - Biosimilars matched reference products for visual acuity, retinal thickness and adverse events across nAMD, DMO, vein occlusion and polypoidal choroidal vasculopathy in a 2026 meta-analysis of 25 studies [S11]. - Bevacizumab and ranibizumab gave similar visual acuity outcomes in nAMD (high-certainty evidence), despite the substantially lower cost of bevacizumab [S4]. - In DMO with worse baseline vision, aflibercept gave better 2-year acuity than bevacizumab; with better baseline vision outcomes were similar [S2]. - Long-term safety data for biosimilars are sparse [S6].

Evidence last checked: 2026-10-18 (PubMed abstracts).

Red flags

• Pain, redness or reduced vision after any anti-VEGF injection, whatever the product: endophthalmitis and retinal haemorrhage were the most frequently documented serious ocular adverse events in biosimilar trials [S6].
• Ocular inflammation or raised IOP after injection, the most frequently reported serious ocular adverse events in the anti-VEGF Cochrane review [S4].
• Long-term use of a biosimilar: the evidence comes mostly from trials with follow-up of 12 to 52 weeks [S6].

Recognise it: what the options are

• Reference products in biosimilar trials were ranibizumab in seven and aflibercept in two studies [S6].
• Aflibercept biosimilars. A meta-analysis of 11 RCTs (4064 participants) found no significant differences in visual acuity change, central subfield thickness, anti-drug antibodies or adverse events in nAMD or DMO [S8].
• Ranibizumab biosimilar example. In a phase 3 equivalence trial of SB11 (705 participants), visual and anatomical outcomes were equivalent, serious adverse events were 12.6% vs 12.4%, and anti-drug antibodies were 3.0% vs 3.1% [S5].
• Bevacizumab biosimilars. In an Indian randomised study of 123 patients with DMO, two bevacizumab biosimilars gave similar acuity and thickness improvements to the originator and were cost-effective [S7].
• Off-label bevacizumab. Across 17 trials, no agent had a clear advantage for effectiveness or safety; aflibercept and ranibizumab were significantly less cost-effective than repackaged bevacizumab in two trials [S3].

Confirm it: judging the evidence

• Biosimilar trials were all industry-supported but judged to be of high methodological standard [S6].
• Evidence is thinner for aflibercept biosimilars than ranibizumab biosimilars in the Cochrane review [S6].
• One DMO trial reported more arterial thrombotic events with ranibizumab than aflibercept [S3]; in a 660-participant DMO RCT, APTC events were 5%, 8% and 12% with aflibercept, bevacizumab and ranibizumab, warranting further evaluation [S2].

Manage it: choosing a product

Before acting on this section, check the national and local guidelines, product information and regulatory approvals that apply where you practise. See the medical disclaimer.

Tier A (primary care / no specialist)

• Tier A does not give injections. Refer patients with suspected nAMD or DMO; explain that lower-cost options exist and give similar results in trials [S4] [S6].

Tier B (general eye clinic)

• Where cost limits access, bevacizumab is a reasonable first choice in nAMD on efficacy grounds [S4], and was the most cost-effective strategy in the UK IVAN trial [S1].
• Biosimilars may be a viable alternative to reference products [S6].
• Doses used in trials, as reported in [S2]: aflibercept 2.0 mg, repackaged bevacizumab 1.25 mg and ranibizumab 0.3 mg for DMO; as reported in [S1]: ranibizumab 0.5 mg or bevacizumab 1.25 mg for nAMD. For practice, follow product labelling and local formularies.
• Repackaged (compounded) bevacizumab was used in the DMO comparative RCT [S2]; compounding standards are not covered by these sources.

Tier C (specialist centre)

• In DMO with worse baseline vision (20/50 to 20/320), consider aflibercept where available, given its better 2-year results vs bevacizumab [S2].
• Retinopathy of prematurity. A systematic review of 5 studies (382 eyes) found an overall adverse event rate of 0.5% and pooled success of 65% with bevacizumab biosimilars and 46% with ranibizumab biosimilars; RCTs against reference products are needed [S10].
• Use cost-effectiveness data with care: estimates vary with model perspective, time horizon and assumptions [S9].

Refer when

Pitfalls

• Assuming biosimilar long-term safety is established [S6].
• Assuming all anti-VEGF agents are interchangeable in DMO with poor baseline vision [S2].
• Comparing cost-effectiveness studies without checking their assumptions [S9].
• Extrapolating ROP biosimilar results, which come from small non-randomised data [S10].

Evidence notes

• All biosimilar RCTs in the Cochrane review were industry-supported [S6]. The SB11 trial was an equivalence design over 48 weeks [S5].
• The Cochrane anti-VEGF review notes trials were too small to estimate differences in rare safety outcomes [S4].
• Cost data from IVAN reflect the UK NHS in 2014 and may not transfer to other settings [S1].
• Not covered by these sources: regulatory approval status by country, switching between biosimilars, interchangeability rules, and aseptic compounding of bevacizumab.

Related articles

• Next-Generation Anti-VEGF and Long-Acting Retinal Drugs
• Diabetic Macular Oedema

References

See the numbered source list below. Each marker [S#] links to its PubMed and DOI record.