Real-world outcomes with aflibercept better in treatment-naïve patients

The global burden of neovascular age-related macular degeneration (AMD) is expected to increase as the population ages, and (to date) the anti-vascular endothelial growth factor (VEGF) drugs are considered first-line treatment, based on the results from numerous pivotal studies. Those studies led to the approval of both aflibercept and ranibizumab (and pegaptanib, although that compound is rarely used as a first-line treatment these days).

Evidence remains strong that this class of drug is both efficacious and safe across a wide range of neovascular AMD patients.

What about real-world outcomes?

Clinicians do not yet know if treat-and-extend, PRN, or some other dosing regimen is best. Conflicting reports suggest that when anti-VEGF therapy is stopped, the clinical aspects of the disease return sooner than anticipated, making a case for continual monthly dosing.

Investigating the effectiveness of aflibercept (Eylea, Regeneron) in patients with wet AMD, (PERSEUS) is a prospective, observational, non-controlled, multicenter cohort study to describe follow-up and treatment patterns in routine practice in 942 patients with AMD (treatment-naïve or previously treated) across 66 clinics in Germany. “Previously treated” in this study meant patients who received any pre-treatment.
 

Study background

Study background

PERSEUS also sought to evaluate subgroups of participants based on treatment patterns.

Though the study is designed to follow patients for 24 months, Nicole Eter, MD, professor of ophthalmology, University of Muenster Medical Center, Muenster, Germany, et al. recently highlighted the 12-month interim results.¹

Six-month interim results were presented last year.^2,3

Subjects were eligible for enrollment if they had neovascular AMD and were treated with aflibercept according to the European label (intravitreal injections every 8 weeks after a 3-month loading dose). There were 802 patients available with 12-month data (447 treatment-naïve and 355 previously treated). Eter et al. also reported on outcomes with regular injection intervals (+4/-2 weeks) following three monthly (+2/-1 week) injections, and compared those results with patients who had irregularities in treatment regimens.

At baseline, patient characteristics were fairly well matched, Dr. Eter noted, with a mean age of 77.7 overall (77.5 in the treatment-naïve group and 78.0 in the previously treated group).

Most patients did not have a baseline fluorescein angiography, but most patients had occult lesions with no chronic lesions (31.1% in the treatment-naïve group and 18.3% in the previously treated group).

Mean letter scores were relatively similar as well--53.4 in the treatment-naïve group and 52.9 letters in the previously treated group. More than 90% of patients in both groups had public health insurance.

Trial results

Trial results

At month 4, mean visual acuity in the treatment-naïve group (n = 328) improved by 6.2 letters, and had improved in the previously treated group (n = 283) by 2.6 letters. At month 12, however, mean visual acuity in the treatment-naïve group improved by 5.3 ± 17.4 letters (n = 374) and decreased by -0.1 ± 15.6 letters in the pre-treated group (n = 311).

In the overall study group, 26.1% (n = 209) received injections at regular intervals, but irregularities occurred in 593 patients (73.9%). When stratified by treatment regularity, visual acuity improvement was more pronounced in patients who were treated regularly compared with those who were not.

This held for the number of patients with a 15+ letter improvement as well-29.1% in the treatment-naïve group and 15.4% in the previously treated group; 11.8% of the treatment lost 15+ letters compared wih 15.1% of the previously treated group.

Changes in retinal thickness followed along the same lines, with the treatment-naïve group improving by 92 μm compared with the previously treated group, which improved by 58.5 μm. However, irregularities in treatment occurred in 74% of all patients, and the researchers noted “visual acuity improvement was more pronounced in regularly treated patients.”

In the treatment-naïve group, those who received regular treatments saw their visual acuity improve by 30.9%, compared with only 18.7% in those treated irregularly.

Similarly, in the previously treated group, those who were treated regularly had a 10.9% increase in visual acuity compared with a -2.3% loss in vision if they were treated irregularly.

The number of injections and the number of visits were not statistically different between the two groups, Dr. Eter noted, averaging around 9 visits and 6 injections each.

“Injection numbers were lower than what would be expected during treatment in strict accordance to the European intravitreal aflibercept label,” Dr. Eter said.

Overall, 3.5% of all patients experienced non-ocular treatment-emergent adverse events (TEAE), 8.9% experienced ocular TEAEs. Of all patients, 1.9% had a cataract, 1.1% had conjunctival hemorrhage, and 0.7% had corneal erosion. No cases of endophthalmitis were reported (5,211 injections).

References

1. Eter N, Jochmann C, Wiedemann PM, et al. Real-life evidence data on intravitreal usage of/treatment with intravitreal aflibercept in Germany: 12-months results of an observational study in nAMD (PERSEUS). Presented at ARVO 2017. Baltimore, MD: May 7, 2017. Abstract A0298.

2. Framme C, Eter N, Jochmann C, et al. PERSEUS 12-month interim analysis: A prospective non-interventional study to assess the effectiveness of intravitreal aflibercept in routine clinical practice in patients with wet age-related macular degeneration: patient-relevant visual acuity. Presented at EURETINA 2016. Copenhagen, Denmark: Sept. 8-11, 2016. Abstract available at: http://euretina.org/copenhagen2016/programme/posters-details.asp?id=6828 Accessed June 7, 2017.

3. Wachtlin J, Schilling H, Jochmann C., et al. 6-month interim analysis of PERSEUS: A prospective non-interventional study to assess the effectiveness of intravitreal aflibercept in routine clinical practice in patients with wet age-related macular degeneration (wAMD) - outcomes in naïve patients (P,B). Presented at: 29th International Congress of German Ophthalmic Surgeons (DOC). Nuremberg, Germany: June 9-11, 2016. Abstract available at: http://www.egms.de/static/en/meetings/doc2016/16doc076.shtml Accessed June 7, 2017.

Nicole Eter, MD

E: eter@ukmuenster.de

This article was adapted from Dr. Eter’s presentation at the 2017 meeting of the Association for Research in Vision and Ophthalmology. Dr. Eter is a consultant to or has received financial support from Alimera, Allergan, Bayer, Heidelberg Engineering, Novartis, and Roche.