TY - JOUR
T1 - Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema
T2 - the RESTORE extension study
AU - Schmidt-Erfurth, Ursula
AU - Lang, Gabriele E
AU - Holz, Frank G
AU - Schlingemann, Reinier O
AU - Lanzetta, Paolo
AU - Massin, Pascale
AU - Gerstner, Ortrud
AU - Bouazza, Abdelkader Si
AU - Shen, Haige
AU - Osborne, Aaron
AU - Mitchell, Paul
N1 - Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
KW - Angiogenesis Inhibitors
KW - Antibodies, Monoclonal, Humanized
KW - Diabetes Mellitus, Type 1
KW - Diabetes Mellitus, Type 2
KW - Diabetic Retinopathy
KW - Female
KW - Humans
KW - Individualized Medicine
KW - Intravitreal Injections
KW - Laser Coagulation
KW - Macular Edema
KW - Male
KW - Middle Aged
KW - Questionnaires
KW - Retina
KW - Retreatment
KW - Sickness Impact Profile
KW - Time Factors
KW - Treatment Outcome
KW - Visual Acuity
U2 - 10.1016/j.ophtha.2013.11.041
DO - 10.1016/j.ophtha.2013.11.041
M3 - Article
C2 - 24491642
VL - 121
SP - 1045
EP - 1053
JO - Ophthalmology
JF - Ophthalmology
SN - 0161-6420
IS - 5
ER -