November 10, 2008(亞特蘭大) — 兩個第二期試驗的結果顯示，ranibizumab (Lucentis,Genentech藥廠)對於治療糖尿病黃斑部水腫(DME)有效。
約翰霍普金斯大學Wilmer眼科研究中心眼科教授、Peter A. Campochiaro醫師發表READ 2研究的6個月結果，該研究比較DME的不同治療，包括玻璃體內注射ranibizumab 0.5 mg 、病灶雷射治療，與ranibizumab加上病灶雷射治療。
Campochiaro醫師向Medscape Ophthalmology表示，這些結果證明READ 1試驗的發現。他指出，RISE和RIDE第3期試驗將提供有關ranibizumab用於DME效果的更明確資料；他也指出，未來的試驗將使用比現在這個研究更積極的治療規範，可以更改善效力。
在同場會議中發表的另一篇ranibizumab用於DME的試驗中，法國巴黎Lariboisi?re醫院眼科的Pascale Massin醫師報告了RESOLVE第2期試驗的12個月資料，評估玻璃體內注射兩種濃度 ranibizumab用於DME的安全性與效果。
Massin醫師指出，一般認為DME病患的視網膜和玻璃體的視網膜血管內皮細胞成長因子(VEGF)值會高於新血管性老年黃斑病變(neovascular age-related macular degeneration)病患；因此，DME 病患可以從比較高劑量的ranibizumab這種VEGF抑制劑獲利。
此試驗包括了151名中央斑點厚度達300 μm 以上的病患，最佳校正視力(BCVA)字母分數在39-73之間；這些病患有第1或第2型糖尿病，且至少一個眼睛中間發生DME (集中或者擴散)。
當把兩種劑量的ranibizumab 資料整合(n= 77)，且與佯裝組(n= 32)進行比較，整合組的平均BCVA 差異為6.7 (P= .0002)；同樣地，整合組之中央視網膜厚度減少程度也大於佯裝組。
Massin醫師向Medscape Ophthalmology表示，這些結果顯示出減少中央視網膜厚度與改善DME病患視力的效果， 也幫助確認了初步的READ 1 和READ 22的結果。
主持該段會議且擔任READ 2執行委員會的Jennifer Lim醫師向Medscape Ophthalmology表示，RESOLVE試驗的發表是令人著迷的，因為我們已經知道DME病患的VEGF相當高，這使得ranibizumab的劑量也相對的需要高一些。這對此一議題來說是全新的，也使得這篇發表成為此段會議中的最佳表現。
READ2研究接受少年糖尿病研究基金會之贊助，Genentech藥廠提供研究用的藥物。RESOLVE試驗接受Novartis藥廠支持。Campochiaro醫師接受製造ranibizumab的Genentech藥廠的研究資金。Massin 醫師宣稱與Eli Lilly、Fovea Pharmaceuticals、Novartis、Solvay與Takeda等藥廠有財務利益關係。Lim醫師接受Genentech藥廠的教育活動資金，且她擔任Genentech、Eyetech/OSI、Pfizer、Allergan與Novartis的諮商顧問。
November 10, 2008 (Atlanta, Georgia) — Results of 2 phase?2 trials suggest a benefit for ranibizumab (Lucentis, Genentech) in the treatment of diabetic macular edema (DME).
The findings were presented in an oral session here at the 2008 Joint Meeting of the American Academy of Ophthalmology and the European Society of Ophthalmology.
Peter A. Campochiaro, MD, professor of ophthalmology at the Wilmer Eye Institute at Johns Hopkins University, in Baltimore, Maryland, presented 6-month findings from the READ?2 study, which is comparing, in subjects with DME, the effects of intravitreal ranibizumab 0.5?mg with focal laser treatment and a combination of ranibizumab plus focal laser treatment.
Patients were included if they had foveal thickness of at least 250?μm on ocular coherence tomography. Previous treatment was allowed if it had been given at least 3 months prior to study entry (at least 2 months with antiangiogenic agents). Of the 126 patients, 115 completed the study visit at month 6. The results from this population were presented at the meeting.
Improvement in visual acuity of at least 3 lines was observed in 9 patients in the ranibizumab group, compared with 5 in the combination group and 0 in the laser-only group. Visual acuity improved by a mean of 8 letters in the ranibizumab group and 3.8 letters in the combination group; there was a 1-letter loss in the laser-only group. No drug or laser-related adverse events were reported.
"These results substantiate the findings of the READ?1 trial," Dr. Campochiaro told Medscape Ophthalmology. "The RISE and RIDE phase?3 trials will provide more definitive data regarding the effects of ranibizumab in DME," he added. He also noted that future trials will use a more aggressive treatment protocol than the one used in this study, which could further improve efficacy.
In another trial of ranibizumab in DME presented during the same session, Pascale Massin, MD, from the Department of Ophthalmology at the Lariboisiere Hospital, in Paris, France, reported 12-month data from the RESOLVE phase?2 trial, which evaluated the safety and efficacy of 2 concentrations of intravitreal ranibizumab in DME.
Dr. Massin noted that retinal vascular endothelial growth factor (VEGF) levels might be "considerably higher" in the retina and vitreous of patients with DME than in patients with neovascular age-related macular degeneration; therefore, DME patients could benefit from a higher dose of ranibizumab, a VEGF inhibitor.
The trial included 151 patients with central macular thickness of 300 μm or more and a best corrected visual acuity (BCVA) letter score of between 39 and 73. Patients had type?1 or type?2 diabetes mellitus and DME with center involvement in at least 1 eye (focal or diffuse).
Subjects were randomized to receive 3 monthly injections with either 0.3 or 0.5?mg ranibizumab or placebo (sham group). Treatment was then administered on an as-needed basis, depending on response to initial treatment. If edema resolution was incomplete, then the dose of ranibizumab was doubled after 1 month. Photocoagulation after 3 injections was given if needed.
Ranibizumab was superior to placebo with respect to changes in BCVA letter score and central retinal thickness. The safety profile of ranibizumab was comparable to that observed in patients with age-related macular degeneration, Dr. Massin said.
When the pooled data from the doubled-dose ranibizumab group (n?= 77) were compared with the sham group (n?= 32), the difference in mean average change in BCVA was 6.7 for the pooled group (P?= .0002). Likewise, the reduction in central retinal thickness was higher in the pooled-dose group than in the sham group.
"These results demonstrate the efficacy of ranibizumab in decreasing retinal thickness and improving visual acuity in DME, and also help confirm the preliminary READ?1 and 2 results," Dr. Massin told Medscape Ophthalmology.
Jennifer Lim, MD, who moderated the session and serves on the READ?2 Executive Committee, told Medscape Ophthalmology that the presentation of the RESOLVE trial "was fascinating because it is well known that the VEGF levels in DME are much higher, and it makes sense that the dose of ranibizumab needed would be correspondingly higher. This might be breaking new ground with respect to this issue, and this presentation won best in session because of it."
The READ?2 study is funded by the Juvenile Diabetes Research Foundation, and the study drug was provided by Genentech. The RESOLVE trial is supported by Novartis. Dr. Campochiaro has received grants for clinical research from Genentech, the maker of ranibizumab. Dr. Massin has disclosed financial interests or relationships with Eli Lilly, Fovea Pharmaceuticals, Novartis, Solvay, and Takeda. Dr. Lim has received grants for educational activities from Genentech, and she has served as an advisor or consultant to Genentech, Eyetech/OSI, Pfizer, Allergan, and Novartis.
2008 Joint Meeting of the American Academy of Ophthalmology (AAO) and the European Society of Ophthalmology (SOE): Scientific Session PA015 and PA016. Presented November 9, 2008.