Variable Lucentis dosing strategies for wet AMD

As-needed treatment with Lucentis can provide results similar to monthly dosing

The PrONTO (Prospective optical coherence tomography imaging of patients with intraocular ranibizumab) study was designed to investigate the possibility of reducing the frequency of treatment with Lucentis in patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). The study showed that as-needed treatment with Lucentis can provide results similar to monthly dosing.

STUDY DESIGN

Forty patients with AMD-related CNV were enrolled in the study. The mean visual acuity (VA) was 20/80. Patients received 3 monthly injections of Lucentis. Thereafter, treatments were only performed if one of following criteria were met:

1. Loss of 5 letters of acuity with fluid in the macula detected by optical coherence tomography (OCT)
2. An increase in retinal thickness, new hemorrhage, new CNV, or persistent fluid detected by OCT.

After one year, the study was modified such that retreatment was performed if any qualitative OCT change suggestive of recurrent fluid was seen, including new macular cysts, new subretinal fluid, or enlargement of a retinal pigment epithelial detachment.

RESULTS

Full 2-year results are available for 37 patients. Visual acuity and retinal thickness improved within 2 weeks of the initiation of Lucentis treatment. These improvements were then sustained over the 24 months of the study.

Over the 2 years, the average number of injections was 9.9, just about 5 per year. Discounting the first 3 mandatory injections, the average rate of injection was approximately once every 3 months.

All lesion types (classic, occult, etc) responded the same way to treatment.

COMPARING RESULTS

In PrONTO, patients experienced a mean improvement in visual acuity of 11.1 letters at 24 months, compared with a mean gain of 6.6 letters in MARINA (Minimally classic/occult trial of the anti-VEGF antibody ranibizumab in the treatment of neovascular AMD) and 10.7 letters in ANCHOR (Anti-VEGF antibody for the treatment of predominantly classic choroidal neovascularization in AMD). There was no statictically significant difference among the 3 studies in those patients that gained at least 15 letters from baseline.

OCT changes occur very rapidly after Lucentis treatment, as early as 1 day in the PrONTO study, and the change at 1 week is nearly identical between the PrONTO and MARINA studies. Variable dosing yielded results comparable to monthly dosing over 24 months. OCT appears to be useful in guiding retreatment decisions.

RETREATMENT STRATEGIES

Natural history of untreated AMD: Dry AMD progresses from dry to wet or geographic atrophy (Click to enlarge)

The variable dosing strategy used in PrONTO successfully reduced the number of Lucentis treatments in most patients, but it did not reduce the frequency of office visits patients needed to attend. Therefore, other strategies are being explored with the aim of reducing the number of office visits.

In the PrONTO strategy, called "treat and observe," the patient is treated monthly until the macula is dry and observed monthly until fluid reappears. Then treatment is given.

A second strategy is called "treat and extend." Here, the patient is treated until the macula is dry, and then treatment is continued while the interval between follow-up exams is extended. So, for instance, if the patient is dry 1 month after the last injection, another treatment is given, and follow-up would be extended to 6 weeks, and again treatment would be given and follow-up scheduled for 8 weeks. Most often, the extension is stopped at 3 months, and retreatment is given every 3 months. The downside to this option is that patients may be given unnecessary treatments.

NONRESPONDERS

Treatment with Lucentis converts wet AMD back to dry AMD or geographic atrophy (Click to enlarge)

In both MARINA and ANCHOR, approximately 10% of patients lost at least 3 lines of visual acuity. In order to try to determine why these patients lost vision, lesion characteristics of the patients that lost vision were compared with those that gained vision. In most patients, visual acuity loss did not result from continuation of neovascularization - almost all of the patients who lost vision had dry maculas.

Lucentis essentially took the wet form of the disease and converted it back to dry (See Figures). It seems likely that the progression of the dry macular degeneration is responsible for the vision loss in the 10% of patients who lost vision.

CONCLUSIONS

Variable dosing strategies with Lucentis can improve vision. OCT-guided retreatment strategies, with the goal of a dry macula, are a promising alternative to mandated monthly injections.

SOURCE