PMID- 23021093 OWN - NLM STAT- MEDLINE DCOM- 20130307 LR - 20220311 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 120 IP - 1 DP - 2013 Jan TI - The SECURE study: long-term safety of ranibizumab 0.5 mg in neovascular age-related macular degeneration. PG - 130-9 LID - S0161-6420(12)00660-4 [pii] LID - 10.1016/j.ophtha.2012.07.026 [doi] AB - OBJECTIVE: To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). DESIGN: Twenty-four-month, open-label, multicenter, phase IV extension study. PARTICIPANTS: Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. METHODS: Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion). MAIN OUTCOME MEASURES: Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections. RESULTS: Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline. CONCLUSIONS: The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment. 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 - Silva, Rufino AU - Silva R AD - Department of Ophthalmology, Coimbra University Hospital, Faculty of Medicine, University of Coimbra, and Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal. rufino.silva@oftalmologia.co.pt FAU - Axer-Siegel, Ruth AU - Axer-Siegel R FAU - Eldem, Bora AU - Eldem B FAU - Guymer, Robyn AU - Guymer R FAU - Kirchhof, Bernd AU - Kirchhof B FAU - Papp, Andras AU - Papp A FAU - Seres, Andras AU - Seres A FAU - Gekkieva, Margarita AU - Gekkieva M FAU - Nieweg, Annette AU - Nieweg A FAU - Pilz, Stefan AU - Pilz S CN - SECURE Study Group LA - eng SI - ClinicalTrials.gov/NCT00504959 PT - Clinical Trial, Phase IV PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20120925 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antibodies, Monoclonal, Humanized) RN - ZL1R02VT79 (Ranibizumab) SB - IM CIN - Ophthalmology. 2013 Sep;120(9):e68-9. PMID: 24001549 CIN - Ophthalmology. 2013 Sep;120(9):e69. PMID: 24001550 MH - Aged MH - Angiogenesis Inhibitors/administration & dosage/*adverse effects MH - Antibodies, Monoclonal, Humanized/administration & dosage/*adverse effects MH - Cataract/chemically induced MH - Double-Blind Method MH - Female MH - Follow-Up Studies MH - Humans MH - Intraocular Pressure/drug effects MH - Intravitreal Injections MH - Male MH - Ocular Hypertension/chemically induced MH - Prospective Studies MH - Ranibizumab MH - Retinal Hemorrhage/chemically induced MH - Visual Acuity/drug effects/physiology MH - Wet Macular Degeneration/*drug therapy/physiopathology FIR - Leys, Anita IR - Leys A FIR - Rakic, Jean-Marie IR - Rakic JM FIR - Postelmans, Laurence IR - Postelmans L FIR - Guymer, Robyn IR - Guymer R FIR - Papp, Andras IR - Papp A FIR - Facsko, Andrea IR - Facsko A FIR - Seres, Andras IR - Seres A FIR - Silva, Rufino IR - Silva R FIR - Falcao Reis, F IR - Falcao Reis F FIR - Schlingemann, R O IR - Schlingemann RO FIR - Hoyng, C P IR - Hoyng CP FIR - Casaroli, Ricardo IR - Casaroli R FIR - Mateo, Carlos IR - Mateo C FIR - Tejerina, Amparo Navea IR - Tejerina AN FIR - Cervera, Enrique IR - Cervera E FIR - Moreno, Jose Ruiz IR - Moreno JR FIR - Lopez, Juan Donate IR - Lopez JD FIR - Ulla, Francisco Gomez IR - Ulla FG FIR - Armada, Felix IR - Armada F FIR - Yang, Yit-Chuijn IR - Yang YC FIR - Bailey, Clare IR - Bailey C FIR - Lotery, Andrew IR - Lotery A FIR - Gibson, Jon IR - Gibson J FIR - Wiedemann, Peter IR - Wiedemann P FIR - Bartz-Schmidt, Karl-Ulrich IR - Bartz-Schmidt KU FIR - Engelmann, Katrin IR - Engelmann K FIR - Holz, Frank IR - Holz F FIR - Kampik, Anselm IR - Kampik A FIR - Kellner, Ulrich IR - Kellner U FIR - Kirchhof, Bernd IR - Kirchhof B FIR - Lemmen, Klaus IR - Lemmen K FIR - Mennel, Stefan IR - Mennel S FIR - Mohr, Andreas IR - Mohr A FIR - Roider, Johann IR - Roider J FIR - Guthoff, Rainer IR - Guthoff R FIR - Foerster, Michael IR - Foerster M FIR - Moisseiev, Joseph IR - Moisseiev J FIR - Goldstein, Michaela IR - Goldstein M FIR - Axer-Siegel, Ruth IR - Axer-Siegel R FIR - Eldem, Bora IR - Eldem B FIR - Ozmert, Emin IR - Ozmert E EDAT- 2012/10/02 06:00 MHDA- 2013/03/08 06:00 CRDT- 2012/10/02 06:00 PHST- 2011/08/30 00:00 [received] PHST- 2012/07/04 00:00 [revised] PHST- 2012/07/10 00:00 [accepted] PHST- 2012/10/02 06:00 [entrez] PHST- 2012/10/02 06:00 [pubmed] PHST- 2013/03/08 06:00 [medline] AID - S0161-6420(12)00660-4 [pii] AID - 10.1016/j.ophtha.2012.07.026 [doi] PST - ppublish SO - Ophthalmology. 2013 Jan;120(1):130-9. doi: 10.1016/j.ophtha.2012.07.026. Epub 2012 Sep 25.