Article Date: 1/1/2008

PrONTO Boosts Hope for Variable Dosing of Ranibizumab
PRESENTATIONS FROM THE RETINA SOCIETY

PrONTO Boosts Hope for Variable Dosing of Ranibizumab

OCT-guided therapy may reduce frequency of injections for some patients.

Among the most eagerly awaited presentations at this year's Retina Society in Boston in September were the 2-year results of the Prospective Optical Coherence Tomography (OCT) Imaging of Patients with Neovascular Age-Related Macular Degeneration (AMD) Treated with Intra-Ocular Ranibizumab (Lucentis, Genentech) study, or the PrONTO study, as it is better known. The results were presented by Philip J. Rosenfeld, MD, PhD, professor of ophthalmology at the Bascom Palmer Eye Institute at the University of Miami. Dr. Rosenfeld first presented these data at the Retinal Physician Symposium in Sanibel, FL, in April 2007.

THE STUDY PROTOCOL

Dr. Rosenfeld reviewed the key questions the PrONTO study sought to answer: How rapidly do OCT and visual acuity (VA) improve? Once the macula is dry, how rapidly does fluid reaccumulate? Once fluid reaccumulates, does it always progress? And can OCT-guided variable dosing sustain improvements in 2-year OCT and VA outcomes?

Dr. Rosenfeld then went over PrONTO study protocol. Monthly dosing with 0.5 mg ranibizumab was done over the first 3 months at baseline, month 1, and month 2. For the next 21 months, there were monthly follow-up visits, with addition injections given only if certainly criteria were fulfilled, ie, loss of ≥5 letters with any fluid by OCT, increase in central retinal thickness ≥100 μm, new hemorrhage or classic choroidal neovascularization (CNV), or persistent fluid detect by OCT 1 month after an injection. Dr. Rosenfeld noted that a key aspect missing in the study design was a monthly dosed control group. Dr. Rosenfeld then discussed the an amendment to the study protocol that took place during year 2 of the study, under which retreatment was now available to a patient with any qualitative OCT change suggestive of recurrent fluid, including new subretinal fluid, macular cysts and the enlargement of retinal pigment epithelial (RPE) detachment.

Philip J. Rosenfeld, MD, PhD, is professor of ophthalmology at Bascom Palmer Eye Institute in Miami. Dr. Rosenfeld reports the following financial relationships: Genentech (speaker, advisory board), Allergan (advisory board), Tanox (advisory board), Genaera (advisory board), Quark (advisory board), Jerini (advisory board), and Carl Zeiss Meditec (travel reimbursement).

THE RESULTS

Out of 40 patients initially enrolled in the PrONTO study based on the inclusion criteria — neovascularization involving the fovea, OCT central retinal thickness ≥300 μm, VA of 20/40 to 20/400 measured using the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart — 3 patients failed to complete 2 years of follow-up.

Dr. Rosenfeld then turned to the quantitative results. There was a mean decrease in central retinal thickness of 210 μm and a mean of 11.1 ETDRS letters gained (median >14 lines). The mean number of injections was 9.9 or 5.0 per year, and the median number was 9.0 or 4.5 per year. These data compared favorably with the results of the MARINA and ANCHOR trials. The PrONTO VA results had the same mean gain of ETDRS letters as the ANCHOR trial (10.7 letters), while PrONTO exceeded the 6.6 ETDRS letter gain from MARINA. The comparison was similar with regard to the percentage of patients who experienced vision gains of ≥15 letters from baseline at the end of 2 years (PrONTO: 43%; MARINA: 33%; and ANCHOR: 41%).

PrONTO was compared only with MARINA for changes in OCT thickness from baseline at week 1, month 1, and year 1. The decreases in PrONTO thickness were better than those from MARINA (116 vs 84 μm at week 1; 157 vs 105 μm at month 1; and 178 vs 123 μm at year 1), but the average thickness at baseline was greater for PrONTO than MARINA. However, when the resolution of excess retinal thickness measurements were compared at each time point, the 2 studies had very similar outcomes.

CONCLUSION

Dr. Rosenfeld concluded his presentation with some generalizations that could be drawn from the PrONTO results. First, VA and OCT improvement were rapid and OCT changes usually precedes VA changes. Second, an OCT-guided variable-dosing regimen was able to maintain improvements through 2 years. Thus, OCT-guided retreatment appears promising as a way to minimize the number of injections while achieving VA results similar to monthly dosing. A prospective randomized trial is needed to confirm the results from this exploratory study. RP



Retinal Physician, Issue: January 2008