PMID- 23725735 OWN - NLM STAT- MEDLINE DCOM- 20131118 LR - 20151119 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 120 IP - 10 DP - 2013 Oct TI - Two-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema: interim analysis of the RESTORE extension study. PG - 2004-12 LID - S0161-6420(13)00153-X [pii] LID - 10.1016/j.ophtha.2013.02.019 [doi] AB - OBJECTIVE: To evaluate the 2-year safety and efficacy of ranibizumab 0.5 mg in diabetic macular edema (DME). DESIGN: Twenty-four-month, open-label, multicenter, Phase IIIb extension study. PARTICIPANTS: Two hundred forty of 303 patients with visual impairment due to DME who completed the RESTORE core study and entered the extension. METHODS: All patients were eligible to receive ranibizumab 0.5 mg pro re nata (PRN) from month 12 (end of core study) to month 36 based on best-corrected visual acuity (BCVA) stability and disease progression retreatment criteria. Patients were also eligible to receive laser PRN according to Early Treatment Diabetic Retinopathy Study guidelines. A preplanned interim analysis was performed at month 24, stratifying by treatment groups as in the RESTORE core study and referred to as prior ranibizumab, ranibizumab plus laser, or laser groups in the extension. MAIN OUTCOME MEASURES: Incidence of ocular and nonocular adverse events (AEs) and mean change in BCVA. RESULTS: Two hundred twenty patients (92%) completed the month 24 visit. Over 2 years, the most frequent ocular serious AE (SAE) and AE were cataract (2.1%) and eye pain (14.6%), respectively. The main nonocular AEs were nasopharyngitis (18.8%) and hypertension (10.4%). There were no cases of endophthalmitis, and the incidences of nonocular SAEs were low. Of the patients entering the extension, 4 deaths were reported in the second year, none of which were related to study drug or procedure. Mean BCVA gain, central retinal thickness (CRT) decrease, and National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) composite score observed at month 12 were maintained at month 24 (prior ranibizumab: +7.9 letters, -140.6 mum, and 5.6, respectively; prior ranibizumab plus laser: +6.7 letters, -133.0 mum, and 5.8, respectively), with an average of 3.9 (prior ranibizumab) and 3.5 ranibizumab injections (prior ranibizumab plus laser). In patients treated with laser alone in the core study, the mean BCVA, CRT, and NEI VFQ-25 composite score improved from month 12 to month 24 (+5.4 letters, -126.6 mum, and 4.3, respectively), with an average of 4.1 ranibizumab injections. CONCLUSIONS: Ranibizumab 0.5 mg administered according to prespecified visual stability and disease progression criteria was well tolerated, with no new safety concerns identified over 2 years. Overall, an average of 3.8 ranibizumab injections was sufficient to maintain (prior ranibizumab) or improve (prior laser) BCVA, CRT, and NEI VFQ-25 outcomes through the second year. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. CI - Copyright (c) 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Lang, Gabriele E AU - Lang GE AD - Division of Medical Retina and Laser Surgery, Department of Ophthalmology, University of Ulm, Ulm, Germany. Electronic address: gabriele.lang@uniklinik-ulm.de. FAU - Berta, Andras AU - Berta A FAU - Eldem, Bora M AU - Eldem BM FAU - Simader, Christian AU - Simader C FAU - Sharp, Dianne AU - Sharp D FAU - Holz, Frank G AU - Holz FG FAU - Sutter, Florian AU - Sutter F FAU - Gerstner, Ortrud AU - Gerstner O FAU - Mitchell, Paul AU - Mitchell P CN - RESTORE Extension Study Group LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20130529 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antibodies, Monoclonal, Humanized) RN - ZL1R02VT79 (Ranibizumab) SB - IM MH - Adult MH - Angiogenesis Inhibitors/adverse effects/*therapeutic use MH - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use MH - Diabetic Retinopathy/*drug therapy MH - Female MH - Humans MH - Intravitreal Injections MH - Macular Edema/*drug therapy MH - Male MH - Ranibizumab MH - Visual Acuity FIR - Adan Civera, A IR - Adan Civera A FIR - Bailey, C IR - Bailey C FIR - Balestrazzi, E IR - Balestrazzi E FIR - Boyd, S IR - Boyd S FIR - Cervera, E IR - Cervera E FIR - Creuzot-Garcher, C IR - Creuzot-Garcher C FIR - Delle Noci, N IR - Delle Noci N FIR - Devriendt, M IR - Devriendt M FIR - Emmerich, K-H IR - Emmerich KH FIR - Ergin, M IR - Ergin M FIR - Garcia-Arumi, J IR - Garcia-Arumi J FIR - Garweg, J IR - Garweg J FIR - Gerding, H IR - Gerding H FIR - Gillies, M IR - Gillies M FIR - Gonder, J IR - Gonder J FIR - Hansen, L IR - Hansen L FIR - Hasanreisoglu, B IR - Hasanreisoglu B FIR - Jurgens, I IR - Jurgens I FIR - Kapran, Z IR - Kapran Z FIR - Kellner, U IR - Kellner U FIR - Kerenyi, A IR - Kerenyi A FIR - Kertes, P IR - Kertes P FIR - Kirchhof, B IR - Kirchhof B FIR - Kleverling, B J IR - Kleverling BJ FIR - Kloos, P IR - Kloos P FIR - Kurz-Levin, M IR - Kurz-Levin M FIR - Lim, L IR - Lim L FIR - Lanzetta, P IR - Lanzetta P FIR - Maberley, D IR - Maberley D FIR - Massin, P IR - Massin P FIR - Martinez Ciriano, J P IR - Martinez Ciriano JP FIR - Menchini, U IR - Menchini U FIR - Mohr, A IR - Mohr A FIR - Olivier, S IR - Olivier S FIR - Papp, A IR - Papp A FIR - Pesztenlehrer, N IR - Pesztenlehrer N FIR - Ruiz Moreno, J IR - Ruiz Moreno J FIR - Sborgia, C IR - Sborgia C FIR - Schlingemann, R O IR - Schlingemann RO FIR - Schneider, U IR - Schneider U FIR - Schrage, N IR - Schrage N FIR - Seres, A IR - Seres A FIR - Sobaci, G IR - Sobaci G FIR - Spital, G IR - Spital G FIR - Tappeiner, C IR - Tappeiner C FIR - Torrez, R IR - Torrez R FIR - Van, J IR - Van J FIR - Vote, B IR - Vote B FIR - Weber, M IR - Weber M FIR - Wiedemann, P IR - Wiedemann P EDAT- 2013/06/04 06:00 MHDA- 2013/11/19 06:00 CRDT- 2013/06/04 06:00 PHST- 2012/08/14 00:00 [received] PHST- 2013/02/12 00:00 [revised] PHST- 2013/02/14 00:00 [accepted] PHST- 2013/06/04 06:00 [entrez] PHST- 2013/06/04 06:00 [pubmed] PHST- 2013/11/19 06:00 [medline] AID - S0161-6420(13)00153-X [pii] AID - 10.1016/j.ophtha.2013.02.019 [doi] PST - ppublish SO - Ophthalmology. 2013 Oct;120(10):2004-12. doi: 10.1016/j.ophtha.2013.02.019. Epub 2013 May 29.