AZURE: Treat-and-Extend Aflibercept for nAMD Noninferior to Fixed Dosing

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New results from the phase 3 randomized AZURE trial showed treat-and-extend aflibercept 2 mg achieved similar functional and anatomic outcomes to fixed dosing every 8 weeks (Q8W) over 52 weeks among patients with neovascular age-related macular degeneration (nAMD).¹

The included population with nAMD previously completed ≥1 year of treatment under a fixed dosing regimen – now, these results exhibited the noninferiority of treat-and-extend to fixed dosing for the primary endpoint of change in best-corrected visual acuity (BCVA) from baseline to week 52

“AZURE shows that treat-and-extend dosing regimens can be personalized to the needs of each patient and enables them to achieve maintenance of BCVA gains comparable to those achieved with fixed dosing, with comparable safety and while reducing treatment burden,” wrote the investigative team, led by Laurent Kodjikian, department of ophthalmology, Croix-Rousse Teaching Hospital, Hospices Civils de Lyon.

Prior to the AZURE study, investigators cited a lack of data on the preferred intravitreal aflibercept treatment for optimal functional and anatomic outcomes with reduced treatment burden in patients with nAMD.¹ Results from the ARIES trial showed noninferior BCVA outcomes between early-start and late-start treat and extend at week 104.² Meanwhile, the ALTAIR study showed noninferior outcomes between Q2W and Q4W dosing regimens at week 52.³

However, the study team noted neither ARIES nor ALTAIR were able to directly establish if a treat-and-extend regimen would provide similar efficacy to fixed Q8W dosing during the chronic phase of treatment after the first year of fixed dosing aflibercept treatment.¹

The parallel-group, open-label, phase 3b AZURE Trial compared the efficacy and safety of intravitreal aflibercept 2 mg using an individualized treat-and-extend regimen with Q8W dosing in patients with nAMD, who completed ≥1 year of fixed-dosing intravitreal aflibercept treatment. The trial was conducted at 100 study centers in 14 countries in Europe and Canada from September 2015 to June 2020.

Enrolled patients were ≥51 years old and prior treatment had to be initiated with intravitreal aflibercept once per month (–1 month or +2 weeks) for 3 months, followed by intravitreal aflibercept every 6 to 12 weeks. After screening, the study randomly assigned patients (1:1) to receive one of 2 parallel aflibercept treatment groups: treat-and-extend (minimum treatment interval of 8 weeks) or a fixed-dosing regimen (treatment Q8W [± 3 days]).

Of the 470 patients screened in AZURE, 336 were randomized and 332 patients were included in the full analysis set. Among this population, 165 patients were included in the treat-and-extend dosing arm and 167 patients were included in the fixed-dosing arm. From treatment initiation to study baseline, data showed the mean change in BCVA was +9.6 letters in the treat-and-extend group and +8.9 letters in the fixed-dosing group.

Upon analysis, at week 52, the mean BCVA change from baseline was –0.3 and –0.5 letters, respectively (least-squares mean difference, 0.22 letters [95% CI, –1.51 to 1.96]. Compared with the fixed-dosing arm, treat-and-extend achieved a mean change in BCVA at week 52 (prespecified margin of 5 letters; P <.0001 for noninferiority test).

From baseline to week 52, the analysis showed 95.2% (n = 157) of patients in the treat-and-extend arm and 94.0% (n = 157) of patients in the fixed-dosing-arm maintained vision (<15-letter loss), with a treatment difference of 1.1% (95% CI, –3.7 to 6.0). Anatomic outcomes revealed central subfield thickness (CST) in the study eye remained stable throughout the study in both groups. From baseline to week 52, the mean change in CST was –24 µm in the treat-and-extend arm and –33 µm in the fixed-dosing arm.

Among those in the treat-and-extend group, 37% of patients achieved a last treatment interval of ≥12 weeks and 9.1% of patients achieved a last treatment interval of >16 weeks up to week 76. Overall, more than half (55.4%) of those who completed the study in the treat-and-extend group (N = 82) had an extended treatment interval of ≥12 weeks.

Kodjikian and colleagues noted that a treat-and-extend regimen lessens the need for interim monitoring, as the expected timing of the next injection may benefit both patient and clinician. Moreover, they indicated an individualized treatment plan could improve both compliance and patient quality of life.

“AZURE demonstrates that a substantial proportion of patients (37%) could be maintained on treatment intervals of ≥12 weeks, and when treatment intervals are not capped at a maximum of 16 weeks, such as in ARIES and ALTAIR,” investigators wrote.

References

1. _{Kodjikian L, Arias Barquet L, Papp A, et al. Intravitreal Aflibercept for Neovascular Age-Related Macular Degeneration Beyond One Year of Treatment: AZURE, a Randomized Trial of Treat-and-Extend vs. Fixed Dosing. Adv Ther. Published online January 6, 2024. doi:10.1007/s12325-023-02719-3}
2. _{Paul M, Frank GH, Philip H, Edoardo M, Eric S, Helmut A, et al. Efficacy and safety of intravitreal aflibercept using a treat-and-extend regimen for neovascular age-related macular degeneration: the ARIES study. Retina. 2021;41:1911–20.}
3. _{Ohji M, Takahashi K, Okada AA, Kobayashi M, Matsuda Y, Terano Y, et al. Efficacy and safety of intravitreal aflibercept treat-and-extend regimens in exudative age-related macular degeneration: 52- and 96-week findings from ALTAIR. Adv Ther. 2020;37(3):1173–87.}