Ranibizumab Port Delivery System effective alternative for Neovascular Age-Related Macular Degeneration: JAMA

The port delivery system with ranibizumab (PDS) is an innovative drug delivery system that has been approved by the US Food and Drug Administration for the treatment of nAMD in adults who have previously responded to at least 2 anti-VEGF injections. The PDS includes a surgically placed permanent indwelling and refillable ocular implant that provides continuous release of a customized formulation of ranibizumab. The PDS is refilled with ranibizumab in an in-clinic setting approximately every 6 months and compared with the requirement for frequent intravitreal injections, has the potential to lead to a reduction in treatment frequency and monitoring visits. The phase 3 Archway trial evaluating PDS with ranibizumab, 100 mg/mL with fixed refill exchanges every 24 weeks, vs intravitreal ranibizumab, 0.5 mg injections every 4 weeks, demonstrated that continuous ranibizumab delivery via PDS had equivalent visual acuity efficacy to monthly ranibizumab injections and a generally well-tolerated safety profile.

Patients who receive their preferred treatment (ie, through shared decision-making, choice, or assessed preferences) may have higher treatment satisfaction rates, increased adherence and compliance, and superior clinical outcomes. The potential for fewer visits and reduced treatment burden with the PDS vs intravitreal injections may influence patient choice. To evaluate patient preference between PDS and intravitreal injections, a PDS Patient Preference Questionnaire (PPPQ) was developed based on the previously reported Patient Preference Questionnaire. In addition, among the patients in the PDS arms, Margaret A. Chang et al reported the PPPQ whereby they evaluated patient preference in the for the PDS vs intravitreal anti-VEGF injections.

Archway was a phase 3 randomized active-comparator open-label clinical trial conducted at 78 sites in the US. Patients 50 years and older with nAMD diagnosed within 9 months of screening with a documented response to anti-VEGF therapy were included. Of 619 patients screened, 418 were enrolled; 415 were included in the primary analysis and 234 were included in the secondary exploratory analysis. The Archway study ran from September 12, 2019, through primary readout on May 22, 2020.

Patients were randomized 3:2 to PDS with ranibizumab, 100 mg/mL, with fixed refill exchanges every 24 weeks or intravitreal ranibizumab injections, 0.5 mg, every 4 weeks.

Treatment satisfaction was measured using the Macular Disease Treatment Satisfaction Questionnaire in the PDS and intravitreal injection arms at week 40. Patient preference was assessed using the content-validated PDS Patient Preference Questionnaire (PPPQ), which measured the proportion of patients in the PDS arm with monthly monitoring who preferred treatment with the PDS at week 40 over previous intravitreal injections or concurrent fellow-eye injections. Both outcomes were exploratory end points.

The mean (SD) age of participants at baseline was 75.0 (7.9) years; 234 participants (59%) were women and 162 (41%) were men. At week 40, differences in overall treatment satisfaction scores were minimal for the PDS and intravitreal injection.

A total of 234 of 248 patients (94.4%) in the PDS arm were included in the PPPQ analysis. At week 40, almost all patients in the PDS arm preferred treatment via PDS (218 of 234 [93.2%]) vs previous intravitreal injections (3 of 234 [1.3%]), including 172 of 234 (73.5%) with a very strong preference for the PDS.

In patients who received concurrent fellow-eye injections (n = 78), 72 (92.3%) preferred the PDS.

Archway was the first phase 3 trial of the PDS; it demonstrated that longer-acting antiVEGF treatment via the PDS provided equivalent visual acuity efficacy, with some safety concerns unique to the PDS, compared with monthly intravitreal anti-VEGF injections. Patients in both Archway and Ladder reported not only a high overall treatment satisfaction for both the PDS and intravitreal injections, but post hoc analyses did not demonstrate a difference in treatment satisfaction between treatment methods.

Authors found that 93.2% of patients preferred treatment with ranibizumab delivered via the PDS vs only 1.3% of patients who preferred intravitreal injections. In addition, they found that most patients (73.5%) in the PDS group had a very strong preference for the PDS, with the most common reasons for PDS preference being fewer treatments, less discomfort, and less worry or nervousness. This is perhaps unsurprising because many patients receiving repeated intravitreal injections report discomfort and anxiety arising from fear of discomfort and fear and anxiety are commonly given reasons for nonadherence among patients receiving intravitreal anti-VEGF injections. Study found that a similarly high proportion of patients preferred the PDS vs intravitreal injections in the subpopulation of patients with bilateral disease who received concurrent intravitreal injections in the fellow eye.

Given the concerns associated with the safety profile of the PDS, authors performed a subgroup analysis for patients with and without ocular SAEs to assess whether preference for the PDS was driven by those without serious complications. Although patient preference for the PDS was lower in patients with ocular SAEs vs those without, most patients (75.0%) with ocular SAEs preferred PDS treatment.

Long-term and frequent use of intravitreal anti-VEGF injections is associated with substantial burden to patients, caregivers, and health care professionals. However, treatment burden (eg, frequency and length of visits and costs to patients and health care professionals) was another important consideration. These studies highlight the unmet need for improvements in the treatment approach for patients with nAMD. In addition, these findings suggest that patients may prefer less burdensome treatment regimens. Evidence from other treatment settings suggest that saving time and less frequent injection regimen are key reasons underlying patient preference.

Although PDS treatment was preferred over previous intravitreal injections by almost all patients assigned to the PDS, both delivery methods had high treatment satisfaction. Using the content-validated PPPQ in patients with nAMD only assigned to the PDS in Archway, study found that continuous delivery of ranibizumab via the PDS was preferred by almost all patients in the PDS group vs intravitreal injections. Preference for the PDS was supported by findings in patients with bilateral nAMD who received concurrent intravitreal injections in the fellow eye. Most patients assigned to the PDS who experienced ocular SAEs preferred treatment with PDS. The overall results appear to be driven by the perceived reductions in treatment burden reported as the need for fewer treatments, requiring less time for treatment, and less discomfort. Authors previously reported that the PDS had equivalent efficacy and was noninferior to intravitreal anti-VEGF injections in Archway and had a well understood safety profile that needs to be kept in mind. Together with the results of the current analysis, these findings suggest that the PDS could be a meaningful alternative treatment option for patients with nAMD.

Source: Margaret A. Chang, MD, MS; Audrey Kapre, MS; Derrick Kaufman; JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2022.1091