Healio
Healio

American Society of Retina Specialists Meeting
August 29, 2012
2 min read
Save

Visual gains maintained at 36 months in RISE, RIDE studies

LAS VEGAS — Vision gains made in the first 24 months of the RIDE and RISE studies were maintained at 36 months for patients who received active treatment, according to a speaker here. Patients who were switched from sham therapy to active therapy in the final 12 months also achieved gains, but not enough to match 3 years of active therapy.

Perspective from Carl D. Regillo, MD

The RIDE and RISE studies similarly randomized patients 1:1:1 to sham, 0.3-mg Lucentis (ranibizumab, Genentech) and 0.5-mg ranibizumab for treatment of diabetic macular edema to 24 months; from 24 to 36 months, all patients received active treatment. The studies were the basis for the U.S. Food and Drug Administration’s recent approval of 0.3-mg ranibizumab monthly treatment for diabetic macular edema

“The sham injection patients rolled over to 0.5 mg monthly, the 0.3-mg patients stayed at 0.3 mg, and the 0.5 mg stayed at 0.5 mg,” David Brown, MD, told colleagues as he gave 36-month study results at the American Society of Retina Specialists meeting.

There were differences, however, between the 0.3-mg and 0.5-mg groups in arterial thrombotic events and deaths. For example, there were more deaths in the 0.5-mg group but more heart attacks in the 0.3-mg group.

“There is no clear answer whether the higher dose is unsafe based on this study; however, these studies aren’t really powered to determine low level of disease progression,” Brown said.

“We all know there’s a selection bias and you make it into the trial because you’re relatively healthy and we think you can make it 36 months,” Brown said. “Patients in the clinic will be sicker, and any potential effect of therapy will be magnified in a real-world situation.”

The rationale for the FDA’s choice of approving the 0.3-mg dose rather than the 0.5-mg dose is based on theoretical concerns for systemic exposure, according to Brown.

“Rationale was that most of these patients are going to need bilateral treatment; they’re going to be at a high risk of heart attack and stroke,” Brown said, and the lower dose was chosen to potentially lower this risk.

  • Disclosure: Brown served on the steering committee for the RIDE and RISE trials.

Perspective

Back to Top
Carl D. Regillo, MD
Carl D. Regillo, MD

There are several important conclusions that can be drawn from the 36-month RIDE and RISE studies of monthly ranibizumab treatment for center-involving diabetic macular edema (DME). From an efficacy standpoint, the groups originally assigned to active drug maintained the very significant gains from baseline for another year beyond the primary endpoint of 24 months without signs of any ocular toxicity. Furthermore, this ongoing treatment not only resulted in excellent DME control but also provided significant reduction in diabetic retinopathy progression. It even improved the retinopathy scale in many patients, some by two or three steps. This overall disease-altering effect with retinopathy improvement is a first for a local treatment. Lastly, similar to other retinal diseases such as retinal vein occlusions and exudative macular degeneration, DME is best managed with early intervention. The initial sham group that crossed over to receive monthly 0.5 mg of ranibizumab in the third year of the study showed relatively good DME reduction by month 36 but did not end up with visual gains that were close to the two groups that received ranibizumab from the start of the trial.

Carl D. Regillo, MD
OSN Retina Board Member
Disclosures: Regillo receives research grant support from and consults with Genentech.