how new anti-vegf redefine care

PARIS -The arrival of second generation anti-VEGF is upsetting the treatment of macular degeneration linked to the exudative age (DMLA). Moreover, due to prolonged efficiency which makes it possible to reduce injections, but to the price of a higher inflammatory risk. In addition, A presentation during the 131st congress of the French Ophthalmology Society (SFO) returned to the impact of these new approaches^[1].

The therapeutic management of DMLA has been marked in recent years by several substantial changes. For example, the most important of which is undoubtedly the provision of second generation anti-VEGF (Brolucizumab, Faricimab and Aflibercept 8 mg), with administration patterns which allow up to five months of interval between injections.

If these new features will redefine therapeutic management in the AMD. However, for the moment “it remains difficult to lead to a simple algorithm”, as the care has become how new anti-vegf redefine care more complex, stressed the Dre Sarah mrejen (National Hospital Center for Ophthalmology of Fifteen-Vingts, Paris), during its presentation.

Poise tolerance

Adjustments are expected in particular with the use of new anti-vegf. Moreover, after the appearance of a signal of less good tolerance in real life with these drugs, in particular the Brolucizumab. Nevertheless, An observation which leads to questioning the best strategy to follow. In addition, in particular after the appearance of one of intraocular inflammation under second generation anti-VEGF.

DMLA is characterized by a progressive degeneration of the Macula, central part of the retina. Furthermore, It is the main cause of vision loss in the elderly. In addition, In the wet form. For example, also called exudative (about 10 % of cases), blood vessels develop abnormally in the macula and lead to a rapid loss of central vision.

Treatment of damp DMLA is based on intravitrean injections how new anti-vegf redefine care of an anti-vegf drug under local anesthesia. Nevertheless, Ranibuzumab and AfliberCept 2 mg are the first to have been used in this indication. For example, The scheme is based on an induction phase of three consecutive monthly injections. However, then reinjections in maintenance, depending on the activity of the disease.

These anti-VEGFs have allowed better control of the disease. Nevertheless, but between 20 to 25% of patients require an intravitrean injection at least every two months, said the ophthalmologist. Nevertheless, To improve the duration of action and avoid loss of compliance in these patients, other anti-VEGFs have been developed.

“More important” drying “

The Brolucizumab is the first second generation anti-vegf to have obtained an AMM in this indication in 2020. In addition, It is a fragment of antibodies “which targets all the ISOFORMS of the VEGF-A”, specifies the speaker. Moreover, Phase III tests HAWK et HARRIER were how new anti-vegf redefine care able to demonstrate his non-inferiority in relation to the reference treatment by. For example, AfliberCept 2 mg ^[2].

AfliberCept 2mg and Brolucizumab were administered at the rate of monthly injection during the first three months of induction. Nevertheless, The Brolucizumab was then administered every two to three months depending on the activity of the disease. while the Aflibercept was administered every two months during this maintenance phase.

The results show a non-inferiority of the Brolucizumab in terms of visual acuity to a year. which is then maintained up to two years. “The efficiency appears above anatomical level, with a greater drying” in the group receiving the anti-vegf antibodies. More than 75% of patients under Brolucizumab were able to keep an interval of 3 months between two injections.

The Faricimab is a bispecific antibody which targets both the vegf-a and the angiopietine 2 (Ang-2). Its non-inferiority compared to the AfliberCept 2 how new anti-vegf redefine care mg has been demonstrated in the tests Tenaya et LUCERNE ^[3]. After an induction phase at the rate of a monthly injection. the Faricimab was then injected every two to four months depending on the activity of the disease.

The non-inferiority of Faricimab on visual acuity compared to the AfliberCept 2 mg was maintained at two years in. the two studies. At two years old. the interval between two injections of Faricimab was three or four months in 71% of patients in the Tenaya trial and 81% in Lucerne. The reference treatment with AfliberCept 2mg was administered every two months.

Finally, the 8mg AfliberCept was compared to the AfliberCept 2 mg in the test PULSAR^[4]. After the induction phase of three monthly injections. patients receiving the AfliberCept 8mg were able to go to injections every two to four months depending on the activity of the disease.

There too, the non-inferiority how new anti-vegf redefine care of the 8mg AfliberCept is demonstrated. At two years, 88% of patients under AfliberCept 8mg have an injection interval of at least three months.

How new anti-vegf redefine care

Favor first generation anti-VEGF

These three molecules are now indicated. in the same way as the first generation anti-VEGF, in the first-line treatment of the exudative DMLA, but different administration patterns. For Faricimab. the interval between injections cannot exceed four months in maintenance, against five months for the Brolucizumab and the AfliberCept 8 mg.

Studies. however, reported later on different tolerance profiles, less favorable with the injections of Brolucizumab, associated with intraocular inflammation “more frequent and more severe”, including retinal vascular occlusions, said Dr. Mrejen. “They also occur later, after six to eight months of treatment.”

Regarding Faricimab and AfliberCept 8 mg, intraocular inflammation “are rare and reversible in the majority of cases”. They generally appear at the start of how new anti-vegf redefine care treatment “after two, three or four injections”. An observation which remains to be confirmed in real life with the AfliberCept 8 mg, “for which we have less perspective”.

These characteristics bring to reconsider the place of these new molecules. “First generation anti-vegf remain a good choice for a first intention,” said Dre Mrejen. Ranibuzumab and AfliberCept 2 mg “have an excellent tolerance profile and very good efficiency”.

The second -line brolicizumab?

The arrival of the biosimilars of first-generation anti-VEGFs. less expensive, but still little used, is also an argument in favor of the priority of these molecules. Ranibizumab biosimilars have been available since 2023. Those of AfliberCeppt should appear on the market in 2026.

Nevertheless. after the induction phase with these first generation molecules, “if fluid control [maculaires] It is not optimal or if it is difficult to space injections of more than two months, it is better how new anti-vegf redefine care to move to second generation molecules which have greater efficiency. »»

Among these second generation anti-vegfs, the Broolicizumab takes a special place, due to its less satisfactory tolerance profile. “It is to be reserved for second -line treatment, especially in the more severe forms of DMLA”. The Faricimab. the AfliberCept 8 mg, better tolerated than the Broolicizumab, are not recommended in first intention “in the event of inflammation history”.

In all cases. Additionally, the use of these new anti-vegf implies personalized care, with in particular a search for the history of inflammation before prescription, underlined the specialist.

“It also takes a time of exchange with the patient to properly explain the signs of alert of intraocular inflammation”. The appearance of pain. redness, myodesopsia (appearance of floating filaments in the visual field) or a decrease in visual acuity must lead to consulting urgently.

Apply the precautionary principle

If an how new anti-vegf redefine care inflammation under second generation anti-VEGF is noted. the opinions are still shared on the process to follow to avoid aggravation towards an occlusive retinal vasculitis. This was revealed by an exchange that followed the presentation between the stakeholders who participated in this session devoted. to the exudative DMLA.

For Dr. Mrejen, the appearance of intraocular inflammation must lead, once it is absorbed, to move to a first generation molecule. For its part. the Dr Maté roast (Paris) believes that this therapeutic switch must depend on the severity of inflammation, taking into account in particular the reluctance of patients at the idea of having more frequent injections.

The PRE Stéphanie Baillif (CHU de Nice). a moderator of the session, recalled that second generation anti-VEGF inflammations appear mainly in the induction phase, “after the first two or three monthly injections”. According to her, patients then easily agree to move to a first how new anti-vegf redefine care generation molecule.

The risk also depends on the anti-VEGF used. In the event of inflammation under Brolizumab. the transition to another second generation anti-VEGF (Faricimab or AfliberCept 8 mg) can be envisaged. But, not the opposite. While waiting to have more data in real life to orient the strategies. it is better to apply the precautionary principle by promoting the best tolerated molecules, estimates the pre Baillif.

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