PMID- 31079057 OWN - NLM STAT- MEDLINE DCOM- 20200728 LR - 20200728 IS - 1468-2079 (Electronic) IS - 0007-1161 (Print) IS - 0007-1161 (Linking) VI - 104 IP - 1 DP - 2020 Jan TI - Safety and tolerability of ranibizumab in uni/bilateral neovascular age-related macular degeneration: 12-month TWEYEs study. PG - 64-73 LID - 10.1136/bjophthalmol-2019-313907 [doi] AB - BACKGROUND: To evaluate the safety and tolerability of ranibizumab 0.5 mg in patients with uni/bilateral neovascular age-related macular degeneration (nAMD) and best-corrected visual acuity (BCVA)<2/10 and/or second eye affected, regardless of BCVA. METHODS: In this 12-month, prospective, multicentre, open-label, single arm, pragmatic interventional study, patients (N=941) aged >/= 50 years were to receive ranibizumab as per approved label, monthly until maximum stable visual acuity (VA) was achieved (initially, three or more injections may be required). Thereafter, patients were to be monitored monthly for VA and treatment was to be resumed if VA was reduced due to disease activity. RESULTS: Of the 936 patients treated with ranibizumab at least once during the study, 823/113 were unilaterally/bilaterally (not simultaneously) treated . The mean (SD) number of ranibizumab injections during the study was 5.4 (2.9)/10.6 (5.0) injections in uni/bilaterally treated patients. Three systemic drug-related adverse events (AEs) (all serious, all in unilaterally treated patients) and 18 systemic AE of special interest (AESIs) (11 serious, 16/2 in unilaterally/bilaterally treated patients) occurred during the study. The annual incidence rate (AIR) (events/1000 person-years) for systemic drug-related AEs, considering a 15-day/30-day risk period, 11.0/8.5 for unilaterally treated patients. Considering the same risk period, the AIR (events/1000 person-years) for systemic AESIs for unilaterally treated patients was 22.1/19.9. Considering a 30-day risk period, the AIR (events/1000 treated eye-years) of ocular drug-related AEs was 23 and AESIs was 11.5. CONCLUSIONS: The low incidence of AEs and AESIs demonstrated the good safety and tolerability of ranibizumab in unilaterally/bilaterally treated patients with nAMD in this real-world setting. CI - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Bandello, Francesco AU - Bandello F AUID- ORCID: 0000-0003-3238-9682 AD - Department of Ophthalmology, University Vita Salute Hospital San Raffaele, Milano, Italy bandello.francesco@hsr.it. FAU - Staurenghi, Giovanni AU - Staurenghi G AD - Department of Biomedical and Clinical Science Luigi Sacco, Luigi Sacco Hospital, University of Milan, Milan, Italy. FAU - Ricci, Federico AU - Ricci F AD - UOSD Patologie Retiniche, Policlinico Tor Vergata, University Tor Vergata, Rome, Italy. FAU - Midena, Edoardo AU - Midena E AD - Department of Ophthalmology, University of Padua, Padova, Italy. FAU - Viola, Francesco AU - Viola F AD - Department of Clinical Sciences and CommunityHealth, University of Milan, Ophthalmological Unit, IRCCS-Ca GrandaFoundation-Ospedale Maggiore Policlinico, Milano, Italy. FAU - Lupieri Sinibaldi, Tommaso AU - Lupieri Sinibaldi T AD - Novartis Farma S.p.A, Largo Umberto Boccioni, Origgio, Origgio, Italy. FAU - Colombo, Laura AU - Colombo L AD - Novartis Farma S.p.A, Largo Umberto Boccioni, Origgio, Origgio, Italy. FAU - Peruzzi, Elena AU - Peruzzi E AD - Novartis Farma S.p.A, Largo Umberto Boccioni, Origgio, Origgio, Italy. FAU - Bassanini, Stefania AU - Bassanini S AD - Novartis Farma S.p.A, Largo Umberto Boccioni, Origgio, Origgio, Italy. LA - eng PT - Journal Article PT - Multicenter Study PT - Pragmatic Clinical Trial DEP - 20190511 PL - England TA - Br J Ophthalmol JT - The British journal of ophthalmology JID - 0421041 RN - 0 (Angiogenesis Inhibitors) RN - ZL1R02VT79 (Ranibizumab) SB - IM MH - Aged MH - Aged, 80 and over MH - Angiogenesis Inhibitors/administration & dosage/*adverse effects/therapeutic use MH - Choroidal Neovascularization/drug therapy/epidemiology/physiopathology MH - Drug Administration Schedule MH - Drug-Related Side Effects and Adverse Reactions/epidemiology/etiology MH - Female MH - Humans MH - Incidence MH - Intravitreal Injections MH - Italy/epidemiology MH - Male MH - Middle Aged MH - Prospective Studies MH - Ranibizumab/administration & dosage/*adverse effects/therapeutic use MH - Risk Assessment/methods MH - Tomography, Optical Coherence MH - Visual Acuity/drug effects MH - Wet Macular Degeneration/*drug therapy/epidemiology/physiopathology PMC - PMC6922014 OTO - NOTNLM OT - age-related macular degeneration OT - bilateral AMD OT - neovascular age-related macular degeneration OT - neovascularisation OT - retina OT - unilateral AMD OT - vision COIS- Competing interests: FB: Consultant-Acucela (Seattle, Washington), Alcon (Fort Worth, Texas), Bayer (Leverkusen, Germany), Boehringer-Ingelheim (Ingelheim, Germany), Genentech (South San Francisco, California), Heidelberg Engineering (Heidelberg, Germany), Novartis (Basel, Switzerland), Roche (Basel, Switzerland) and Zeiss (Oberkochen, Germany); Financial support-Bayer (Leverkusen, Germany), Genentech (South San Francisco, California), Heidelberg Engineering (Heidelberg, Germany), Novartis (Basel, Switzerland), Roche (Basel, Switzerland) and Zeiss (Oberkochen, Germany). GS: Consultant-Novartis (Basel, Switzerland), Bayer HealthCare (Leverkusen, Germany), Allergan (Dublin, Ireland), Genentech (South San Francisco, California), Roche (Basel, Switzerland), Heidelberg Engineering (Heidelberg, Germany) and Alcon (Fort Worth, Texas); Financial support-Bayer HealthCare (Leverkusen, Germany), Centervue (Padova, Italy), Heidelberg Engineering (Heidelberg, Germany) and Novartis (Basel, Switzerland); Lecturer-Zeiss (Oberkochen, Germany); Patent holder-in conjunction with Ocular Instruments, Inc. (Bellevue, Washington); Payment for development of educational presentations-Roche (Basel, Switzerland). FR: Alcon (Fort Worth, Texas), Bayer (Leverkusen, Germany), Novartis (Basel, Switzerland), Roche (Basel, Switzerland), Allergan (Dublin, Ireland), SIFI (Catania, Italy). FV: Consultant-Novartis (Basel, Switzerland), Bayer HealthCare (Leverkusen, Germany), Financial support-Allergan (Dublin, Ireland), Novartis (Basel, Switzerland), Bayer HealthCare (Leverkusen, Germany), SIFI (Catania, Italy). TLS: Employee-Novartis Farma S.p.A (Origgio, Italy) at the time of development of the manuscript and submission. EP, SB: Employees-Novartis Farma S.p.A (Origgio, Italy). LC: Employee-Novartis Farma S.p.A (Origgio, Italy) at the time of development of the manuscript and submission. EDAT- 2019/05/13 06:00 MHDA- 2020/07/29 06:00 PMCR- 2019/12/19 CRDT- 2019/05/13 06:00 PHST- 2019/01/22 00:00 [received] PHST- 2019/03/29 00:00 [accepted] PHST- 2019/05/13 06:00 [pubmed] PHST- 2020/07/29 06:00 [medline] PHST- 2019/05/13 06:00 [entrez] PHST- 2019/12/19 00:00 [pmc-release] AID - bjophthalmol-2019-313907 [pii] AID - 10.1136/bjophthalmol-2019-313907 [doi] PST - ppublish SO - Br J Ophthalmol. 2020 Jan;104(1):64-73. doi: 10.1136/bjophthalmol-2019-313907. Epub 2019 May 11.