Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study
Ursula Schmidt-Erfurth, Gabriele E Lang, Frank G Holz, Reinier O Schlingemann, Paolo Lanzetta, Pascale Massin, Ortrud Gerstner, Abdelkader Si Bouazza, Haige Shen, Aaron Osborne, Paul Mitchell, RESTORE Extension Study Group, Andras Papp, Andras Seres, Andras Berta, Norbert Pesztenlehrer, Michel Weber, Catherine Creuzot- Garcher, Karl-Heinz Emmerich, Katrin Engelmann, Lutz Hansen, Ulrich Kellner, Bernd Kirchhof, Andreas Mohr, Georg Spital, Peter Wiedemann, Norbert Schrage, Ugo Menchini, Emilio Balestrazzi, Nicola Delle Noci, J P Martinez Ciriano, Bert Jeroen Kleverling, Joachim Van Calster, Marlene Devriendt, Malaika Kurz-Levin, Inga Jürgens, Ulrike Schneider, Justus Garweg, Christoph Tappeiner, Heinrich Gerding, Patrik Kloos, Bora Eldem, Gungor Sobaci, Ziya Kapran, Mehmet Ergin, Berati Hasanreisoglu, Josep Garcia Arumi, Francisco Gomez Ulla, Ramon Torres Imaz, Enrique Cervera, Alfredo Adan Civera, Jose Ruiz Moreno, Mark Gillies, Lyndell Lim, Brendan Vote, Dianne Sharp, John Gonder, Peter Kertes, David Maberley, Shelley Boyd, Sébastien Olivier, Clare Bailey, Ursula Schmidt-Erfurth, Gabriele E Lang, Frank G Holz, Reinier O Schlingemann, Paolo Lanzetta, Pascale Massin, Ortrud Gerstner, Abdelkader Si Bouazza, Haige Shen, Aaron Osborne, Paul Mitchell, RESTORE Extension Study Group, Andras Papp, Andras Seres, Andras Berta, Norbert Pesztenlehrer, Michel Weber, Catherine Creuzot- Garcher, Karl-Heinz Emmerich, Katrin Engelmann, Lutz Hansen, Ulrich Kellner, Bernd Kirchhof, Andreas Mohr, Georg Spital, Peter Wiedemann, Norbert Schrage, Ugo Menchini, Emilio Balestrazzi, Nicola Delle Noci, J P Martinez Ciriano, Bert Jeroen Kleverling, Joachim Van Calster, Marlene Devriendt, Malaika Kurz-Levin, Inga Jürgens, Ulrike Schneider, Justus Garweg, Christoph Tappeiner, Heinrich Gerding, Patrik Kloos, Bora Eldem, Gungor Sobaci, Ziya Kapran, Mehmet Ergin, Berati Hasanreisoglu, Josep Garcia Arumi, Francisco Gomez Ulla, Ramon Torres Imaz, Enrique Cervera, Alfredo Adan Civera, Jose Ruiz Moreno, Mark Gillies, Lyndell Lim, Brendan Vote, Dianne Sharp, John Gonder, Peter Kertes, David Maberley, Shelley Boyd, Sébastien Olivier, Clare Bailey
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.
Trial registration: ClinicalTrials.gov NCT00906464.
Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Source: PubMed