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Monotherapy Aflibercept Does Not Differ to Initial Bevacizumab for DME Care

An assessment of anti-VEGF dose regimen strategies concludes with little difference in outcomes among treatment arms at 2 years.

Monotherapy aflibercept (EYLEA) did not provide a significant difference in visual outcomes than bevacizumab over 2 years for patients with diabetic macular edema (DME), according to new data.

In research findings presented at the American Society of Retina Specialists (ASRS) 2022 Annual Meeting today, a team of investigators with the DRCR Retina Network reported bevacizumab, an investigative biologic from Outlook Therapeutics, provided similar improvements in long-term visual acuity as standard-care anti-VEGF aflibercept in patients with DME.

The team, led by Chirag D. Jhaveri, MD, of the Retina Consultants of Austin, sought to interpret the relative efficacy of aflibercept monotherapy compared to initial bevacizumab with a switch to aflibercept among eyes with insufficient approval, in patients with DME.

As they noted, aflibercept and ranibizumab are among the US Food and Drug Administration (FDA)-marketed options for anti-VEGF treatment of DME, the leading cause of vision loss in the US, while bevacizumab—up for consideration later this year—is a lower-cost, off-label option.

“Because the costs of aflibercept and ranibizumab are substantially higher than that of bevacizumab, an increasing number of insurers require step therapy, in which bevacizumab is used for the initial treatment with a switch to another anti-VEGF agent if the clinical response is unsatisfactory,” they wrote. “For eyes with a baseline visual acuity of 20/50 or worse, it is unclear whether this strategy compromises long-term visual acuity relative to aflibercept monotherapy.”

Their analysis included eyes from adult participants at 54 different clinical sites. Eligible eyes had diagnosed DME involving the macular center and a baseline visual acuity (VA) letter score of 24-69. Participants were randomized to either 2 mg intravitreal aflibercept or 1.25 mg intravitreal bevacizumab, with doses at baseline then according to pre-specified regimen protocol. Patient eyes in the bevacizumab arm who did not meet protocol-specified outcomes by week 12 were switched to aflibercept.

Primary outcome was mean change in VA over 2 years, with additional assessments into retinal central subfield thickness (CST) and VA, as well las safety outcomes.

The final assessment included 312 eyes in 270 adults with DME; 158 were assigned to aflibercept and 154 assigned to bevacizumab at baseline. Median patient age was 61 years old, 48% were women, and more than half (53%) were White. Baseline median VA score was 60 letters; median baseline CST was 488 mcm.

At 2 years, 7 in 10 (70%) of the eyes initiated with bevacizumab were switched to aflibercept therapy. Mean improvement in VA was 15.0 letters among aflibercept-monotherapy eyes and 14.0 letters among the initial bevacizumab group at 2 years (adjusted difference, 0.8; 95% CI, -0.9 to 2.5; P = .37).

Investigators additionally observed similar mean changes in VA and retinal CST across the 2 arms— a decrease of 192 mcm and 198, respectively, at 2 years (adjusted difference, -16; 95% CI, -39 to 7). Though reduction in CST was greater in the aflibercept mono therapy group than initial bevacizumab group at 24 and 52 weeks, the percentage of eyes at trial’s end with CST below DME thresholds were similar in the 2 arms: 60% and 55%, respectively (adjusted difference, 4; 95% CI, -12 to 20).

Jhaveri and colleagues reported ≥1 serious adverse event in 52% of the aflibercept monotherapy group and 36% of the initial bevacizumab group (P = .05). Another ≥1 hospitalization was reported in 48% and 32% of the treatment arms, respectively (P = .04).

The team credited the trial for “expanding understanding” on the difference of clinical outcomes in differing anti-VEGF treatment strategies for DME.

“Unsurprisingly, given these findings, the visual-acuity and retinal-thickness outcomes in the current trial appeared to favor aflibercept monotherapy over the bevacizumab-first strategy throughout the first year,” they wrote. “However, rescue treatment with aflibercept mitigated the mean visual and anatomical differences that arose from the initiation of therapy with bevacizumab or aflibercept.”

Investigators concluded the findings were increasingly relevant in the scope of costs for care with anti-VEGF for patients with DME.

“Given the difference between the drugs in cost—by approximately a factor of 26 (Medicare reimbursement, approximately $1,830 for one dose of aflibercept and $70 for one dose of bevacizumab)—the initiation of treatment with bevacizumab could have substantial cost reductions for the health care system,” they wrote.

The study, “Aflibercept Monotherapy or Bevacizumab First for Diabetic Macular Edema,” was published online in the New England Journal of Medicine.