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Ranibizumab provided improvements in visual acuity and DR that were stable over the long term when the drug was administered on an as-needed regimen to patients with diabetic macular edema in the RIDE and RISE trials.
Take-home message: Ranibizumab provided improvements in visual acuity and DR that were stable over the long term when the drug was administered on an as-needed regimen to patients with diabetic macular edema in the RIDE and RISE trials.
By Lynda Charters; Reviewed by Michael J. Elman, MD
Baltimore-Ranibizumab (Lucentis, Genentech) provided improvements in visual acuity and diabetic retinopathy (DR) that were stable over the long term when the drug was administered on an as-needed regimen to patients with diabetic macular edema (DME) in the RIDE and RISE trials, said Michael J. Elman, MD.
Obesity and diabetes have been clearly documented to be growing problems in the United States, according to the Centers for Disease Control and Prevention (CDC) that has tracked the steady and concomitant rise of the two diseases. With obesity defined as a body mass index of 30 kg/m2 and higher, the CDC data showed that the incidence of obesity rose from under 14% in some areas of the country and 14.0% to 17.9% in others in 1994 to 26% and higher by 2010.
With this, the incidence of diabetes during the same time frame almost doubled from less than 4.5% and from 4.5% to 5.9% in some areas in 1994 to 9.0% and over in a substantial portion of the United States, said Dr. Elman, who is in private practice in Baltimore.
Along with those increases come visual loss from DR and its complications including DME, hemorrhage from new vessels, retinal detachment, and neovascular glaucoma. Over the decades the standard treatment for DR, panretinal photocoagulation (PRP), decreased the risk of blindness but was associated with its own serious set of complications.
The RISE and RIDE Studies were designed to bring DME treatment to the next level and also to some additional questions: Can proliferative DR (PDR) be delayed or prevented, the need for PRP delayed, the debilitating side effects of PRP eliminated, and DR reversed? The answers to all those may be “Yes.”
Patients in the RISE and RIDE Studies were randomly assigned to 0.3- or 0.5-mg monthly injections of ranibizumab or sham injections. At month 24, patients in the sham group were allowed to cross over to monthly 0.5-mg ranibizumab injections through month 36.
Dr. Elman explained that 15.4% to 19.7% of patients who were initially randomly assigned to 0.3-mg injections-the dose approved by the FDA-had a clinically significant two-step improvement in the Early Treatment Diabetic Retinopathy Study (ETDRS) severity level as early as month 3 compared with 1.7% to 3.2% in the sham arms (p <0.01), Dr. Elman noted. This improvement continued and stabilized at 18 months in 36.8% to 39.3% of patients.
An example of such a two-step improvement, i.e., from an ETDRS score of 61 to a score of 47, is provided in Figure 1. A proportion of patients (5.1% to 9.4%) also had an improvement of three or more steps that was significant at 12 months. This improvement continued through 36 months in 14.5% to 15.4% of patients.
At the 36-month time point, the patients could enter an open-label extension of the study and receive 0.5-mg injections of ranibizumab as needed based on vision and retinal thickness stability.
Overall, 500 patients entered the open-label extension phase of RIDE and RISE. These patients were followed for a mean of 14.1 months and received a mean of 3.8 annualized ranibizumab injections.
“Nearly 20% of patients in the open-label extension study did not require any further treatment,” Dr. Elman, said. “Of 298 patients followed for 1 year or longer in this arm, 19.5% did not need further treatment.
“The PRN ranibizumab treatment during the extension phase continues to reduce the occurrence of new PDR events and patients continued to show improvement in DR with PRN ranibizumab,” Dr. Elman added.
A new PDR event was defined as the first occurrence of progression from nonproliferative DR to PDR, use of panretinal laser, occurrence of vitreous hemorrhage, identification by ophthalmoscopy, vitrectomy for PDR, and occurrence of iris or retinal neovascularization.
Looking at patients with the longest follow-up at months 36 and 60, 49% and 40% of patients, respectively, had improvements of two or more ETDRS steps and 21% and 11% had improvements of three or more ETDRS steps.
“The population of the RIDE and RISE studies represents the entire spectrum of DR,” Dr. Elman summarized. “Improvement over sham in DR was seen as early as month 3 after the onset of treatment with ranibizumab for two or more steps of improvement or at month 12 for three or more steps of improvement. The improvement in DR was maintained with as-needed administration of ranibizumab.”
Michael J. Elman, MD
This article was adapted from Dr. Elman’s presentation at the 2015 meeting of the Association for Research in Vision and Ophthalmology. Dr. Elman receives financial support from Genentech