Ursula Schmidt-Erfurth1, Gabriele E Lang2, Frank G Holz3, Reinier O Schlingemann4, Paolo Lanzetta5, Pascale Massin6, Ortrud Gerstner7, Abdelkader Si Bouazza7, Haige Shen8, Aaron Osborne7, Paul Mitchell9. 1. Department of Ophthalmology, Medical University Vienna, Vienna, Austria. Electronic address: ursula.schmidt-erfurth@meduniwien.ac.at. 2. Division of Medical Retina and Laser Surgery, Department of Ophthalmology, University Eye Hospital Ulm, Ulm, Germany. 3. Department of Ophthalmology, University of Bonn, Bonn, Germany. 4. Medical Retina Unit and Ocular Angiogenesis Group, Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands; Netherlands Institute for Neuroscience (NIN), Royal Academy of Sciences (KNAW), Amsterdam, The Netherlands. 5. Department of Ophthalmology, University of Udine, Udine, Italy; Istituto Europeo di Microchirurgia Oculare (IEMO), Udine, Italy. 6. Assistance Publique des Hopitaux de Paris, Université Paris Diderot, Ophthalmology Department, Hopital Lariboisiere, Paris, France. 7. Novartis Pharma AG, Basel, Switzerland. 8. Beijing Novartis Pharmaceuticals Co., Ltd., Shanghai, China. 9. Centre for Vision Research (Westmead Millennium Institute), University of Sydney, Sydney, Australia.
Abstract
OBJECTIVE: To evaluate long-term efficacy and safety profiles during 3 years of individualized ranibizumab treatment in patients with visual impairment due to diabetic macular edema (DME). DESIGN: Phase IIIb, multicenter, 12-month, randomized core study and 24-month open-label extension study. PARTICIPANTS: Of the 303 patients who completed the randomized RESTORE 12-month core study, 240 entered the extension study. METHODS: In the extension study, patients were eligible to receive individualized ranibizumab treatment as of month 12 guided by best-corrected visual acuity (BCVA) and disease progression criteria at the investigators' discretion. Concomitant laser treatment was allowed according to the Early Treatment Diabetic Retinopathy Study guidelines. Based on the treatments received in the core study, the extension study groups were referred to as prior ranibizumab, prior ranibizumab + laser, and laser. MAIN OUTCOME MEASURES: Change in BCVA and incidence of ocular and nonocular adverse events (AEs) over 3 years. RESULTS: Overall, 208 patients (86.7%) completed the extension study. In patients treated with ranibizumab during the core study, consecutive individualized ranibizumab treatment during the extension study led to an overall maintenance of BCVA and central retinal subfield thickness (CRST) observed at month 12 over the 2-year extension study (+8.0 letters, -142.1 μm [prior ranibizumab] and +6.7 letters, -145.9 μm [prior ranibizumab + laser] from baseline at month 36) with a median of 6.0 injections (mean, 6.8 injections; prior ranibizumab) and 4.0 (mean, 6.0 injections; prior ranibizumab + laser). In the prior laser group, a progressive BCVA improvement (+6.0 letters) and CRST reduction (-142.7 μm) at month 36 were observed after allowing ranibizumab during the extension study, with a median of 4.0 injections (mean, 6.5 injections) from months 12 to 35. Patients in all 3 treatment groups received a mean of <3 injections in the final year. No cases of endophthalmitis, retinal tear, or retinal detachment were reported. The most frequently reported ocular and nonocular adverse effects over 3 years were cataract (16.3%) and nasopharyngitis (23.3%). Eight deaths were reported during the extension study, but none were suspected to be related to the study drug/procedure. CONCLUSIONS:Ranibizumab was effective in improving and maintaining BCVA and CRST outcomes with a progressively declining number of injections over 3 years of individualized dosing. Ranibizumab was generally well tolerated with no new safety concerns over 3 years.
RCT Entities:
OBJECTIVE: To evaluate long-term efficacy and safety profiles during 3 years of individualized ranibizumab treatment in patients with visual impairment due to diabetic macular edema (DME). DESIGN: Phase IIIb, multicenter, 12-month, randomized core study and 24-month open-label extension study. PARTICIPANTS: Of the 303 patients who completed the randomized RESTORE 12-month core study, 240 entered the extension study. METHODS: In the extension study, patients were eligible to receive individualized ranibizumab treatment as of month 12 guided by best-corrected visual acuity (BCVA) and disease progression criteria at the investigators' discretion. Concomitant laser treatment was allowed according to the Early Treatment Diabetic Retinopathy Study guidelines. Based on the treatments received in the core study, the extension study groups were referred to as prior ranibizumab, prior ranibizumab + laser, and laser. MAIN OUTCOME MEASURES: Change in BCVA and incidence of ocular and nonocular adverse events (AEs) over 3 years. RESULTS: Overall, 208 patients (86.7%) completed the extension study. In patients treated with ranibizumab during the core study, consecutive individualized ranibizumab treatment during the extension study led to an overall maintenance of BCVA and central retinal subfield thickness (CRST) observed at month 12 over the 2-year extension study (+8.0 letters, -142.1 μm [prior ranibizumab] and +6.7 letters, -145.9 μm [prior ranibizumab + laser] from baseline at month 36) with a median of 6.0 injections (mean, 6.8 injections; prior ranibizumab) and 4.0 (mean, 6.0 injections; prior ranibizumab + laser). In the prior laser group, a progressive BCVA improvement (+6.0 letters) and CRST reduction (-142.7 μm) at month 36 were observed after allowing ranibizumab during the extension study, with a median of 4.0 injections (mean, 6.5 injections) from months 12 to 35. Patients in all 3 treatment groups received a mean of <3 injections in the final year. No cases of endophthalmitis, retinal tear, or retinal detachment were reported. The most frequently reported ocular and nonocular adverse effects over 3 years were cataract (16.3%) and nasopharyngitis (23.3%). Eight deaths were reported during the extension study, but none were suspected to be related to the study drug/procedure. CONCLUSIONS:Ranibizumab was effective in improving and maintaining BCVA and CRST outcomes with a progressively declining number of injections over 3 years of individualized dosing. Ranibizumab was generally well tolerated with no new safety concerns over 3 years.
Authors: Andreas Ebneter; Dominik Waldmeier; Denise C Zysset-Burri; Sebastian Wolf; Martin Sebastian Zinkernagel Journal: Graefes Arch Clin Exp Ophthalmol Date: 2016-10-07 Impact factor: 3.117
Authors: Susan B Bressler; Danni Liu; Adam R Glassman; Barbara A Blodi; Alessandro A Castellarin; Lee M Jampol; Paul L Kaufman; Michele Melia; Harinderjit Singh; John A Wells Journal: JAMA Ophthalmol Date: 2017-06-01 Impact factor: 7.389