Activity Transcript

Nancy M. Holekamp, MD: Tom is like many patients who are receiving intravitreal anti-VEGF injections for AMD.

We know that these therapies are highly effective for preventing vision loss due to the macular neovascularization and fluid leakage that can occur as AMD progresses. And they have been shown to be safe for the majority of patients. For those reasons, they are now viewed as the standard of care for patients who have developed neovascular AMD.

In real-world patients like Tom, however, the results often fall short of those seen in the clinical trial setting. Anti-VEGF injections must be given on a regular, consistent schedule. Unfortunately,  frequent visits pose a significant burden on patients – and, in many cases, their family or other caregivers. Consequently, a significant proportion of patients initially show a good response to anti-VEGF injections, but then they don’t maintain the necessary frequency of visits. And their vision begins to decline again -- even though we have these great treatments. The AURA study tells us it's a global problem and that, at 2 years, some people’s vision ends up back where they started, or worse, because of undertreatment.

Several studies have explored the reasons why these injections pose such a burden. A survey of 253 patients receiving anti-VEGF injections found that in most cases, the barriers to adherence were numerous and multifactorial. The average number of barriers to treatment reported by patients in that survey was 3.1, with almost half of the patients reporting at least 3 different barriers. So, what are the things that we can do to motivate our patients to adhere to their prescribed treatment regimen? In my experience, it comes down to 3 factors: Number 1 is treatment effect. If we treat patients and they get better, then they’re motivated to come back. Number 2 is the patient-physician relationship. If it becomes a real therapeutic relationship, then patients have confidence in us, and they’re more likely to come back. And number 3 is patient education. If patients understand not only their disease, but the treatment for their disease and the consequences of not getting treated, then they want to come back.

So, of course, we aim to make sure that our patients are on the most effective therapy for them – which means a treatment regimen that they’re willing and able to stick to. And then beyond the treatment effect, we can all help to create a good, open, patient-physician relationship, and we can all help our patients to be adequately educated about their disease and its treatment.

Let’s return to our case, where Tom’s ophthalmologist is going to address the need for good adherence to anti-VEGF therapy…

Dr Holekamp: The reality for patients like Tom is that there are not many good alternatives to anti-VEGF injections. Consequently, there has been an unmet need for effective wet AMD treatment options that sustain the clinical benefits of regular intravitreal anti-VEGF therapy, but without the burden of frequent treatment and monitoring. There has been significant progress in the development of sustained release technology that provides consistent medication over a prolonged period.

The first technology of this kind -- a ranibizumab port delivery system (or ‘PDS’) – was approved last year for the treatment of wet AMD in patients who have responded to at least 2 intravitreal injections of anti-VEGF therapy. It contains 100 mg/mL of ranibizumab -- 20 times the amount in the injectable solution. And this medication is continuously delivered directly into the vitreous cavity over a period of 24 weeks (or approximately 6 months). After 6 months, the implant is refilled in the office.

The effectiveness of the ranibizumab PDS was compared with intravitreal injections of ranibizumab in the Archway trial -- a phase 3 noninferiority and equivalence study involving 418 patients who had previously responded to anti-VEGF therapy. Patients were randomized to receive either the PDS, with refills every 24 weeks, or intravitreal injections every 4 weeks. The change in best-corrected visual acuity from baseline, averaged over weeks 36 and 40, was +0.2 letters in the PDS group and +0.5 letters in the group who received monthly injections. Those findings were within the predetermined noninferiority margin of minus 4.5 letters and the equivalence margin of plus-or-minus 4.5 letters.

Importantly, of the 248 patients who received the PDS implant and were assessed throughout the first 6 months, only 4 patients needed to be given any supplemental injections prior to the first refill exchange at 24 weeks. That is less than 2% of patients.

A bioresorbable hydrogel fiber implant is also in development. This implant is delivered via intravitreal injection and is designed to release medication over a period of around 6 months. It provides axitinib -- a different kind of drug that is not currently used for AMD. Axitinib is a tyrosine kinase inhibitor that acts directly on VEGF receptors. This implant is currently being evaluated in a clinical trial, and initial data have been encouraging.

We’ll look at the most important safety considerations relating to the ranibizumab PDS in a moment. But first, let’s return to the final part of our case, during which Tom’s ophthalmologist is going to describe the implant to him…

Dr. Holekamp: It is important, of course, that we explain to our patients, not only the advantages of sustained-release therapy, but also other important aspects of treatment that should be aware of. For example, we know that for most patients who have the ranibizumab PDS implant, the OCT retinal thickness is controlled, and the vision remains stable. In patients who are VEGF-responsive after injections, we now have data through 96 weeks.  Those data show that both vision and retinal thickness are controlled with the PDS and just a refill exchange procedure in the office every 6 months. However, patients should be aware that it’s normal to experience a transient decrease in vision for the first 4 to 8 weeks, until the eye heals from surgery. In the Archway study, this had generally resolved by the 12-week assessment. Because initial implantation of the ranibizumab PDS is a surgical procedure, the safety considerations are different from intravitreal injections. Prespecified ocular adverse events of special interest were reported in 19% of patients who received the implant, and in 6% of patients in the monthly injections group. The most significant of these events was endophthalmitis. Over time, this occurs in about 2% of patients with the implant.

It's important to treat endophthalmitis promptly, and all patients therefore need to be educated about the signs and symptoms of endophthalmitis, and instructed to immediately report anything that could be associated with these events. It’s also essential for ophthalmologists to routinely monitor the implant and the tissue overlying the implant flange for signs of conjunctival erosion or retraction, so that they can take action if necessary.

In my experience, once the pros and cons of the ranibizumab PDS have been explained to patients they jump at the opportunity to have the implant. And once they have it, they love it. More than 93% of the patients in the ARCHWAY study either strongly or very strongly preferred the implant over injections.

In summary then, most of us who administer intravitreal injections of anti-VEGF therapy to treat wet AMD have encountered patients like Tom who, for a variety of reasons, don’t adhere to the necessary treatment schedule – and subsequently are at risk for losing vision. Sustained delivery technology now allows us to overcome that problem for the majority of patients.

Thank you for watching this Medscape Clinic. Goodbye.