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

doi:10.1016/j.ophtha.2013.11.041

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,

Netherlands Institute for Neuroscience (NIN)

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

291 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1045-53
Number of pages	9
Journal	Ophthalmology
Volume	121
Issue number	5
DOIs	https://doi.org/10.1016/j.ophtha.2013.11.041
Publication status	Published - May 2014

Keywords

Angiogenesis Inhibitors
Antibodies, Monoclonal, Humanized
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Diabetic Retinopathy
Female
Humans
Individualized Medicine
Intravitreal Injections
Laser Coagulation
Macular Edema
Male
Middle Aged
Questionnaires
Retina
Retreatment
Sickness Impact Profile
Time Factors
Treatment Outcome
Visual Acuity

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10.1016/j.ophtha.2013.11.041

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Schmidt-Erfurth, U., Lang, G. E., Holz, F. G., Schlingemann, R. O., Lanzetta, P., Massin, P., Gerstner, O., Bouazza, A. S., Shen, H., Osborne, A., Mitchell, P. (2014). Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology, 121(5), 1045-53. https://doi.org/10.1016/j.ophtha.2013.11.041

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title = "Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study",

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.",

keywords = "Angiogenesis Inhibitors, Antibodies, Monoclonal, Humanized, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Female, Humans, Individualized Medicine, Intravitreal Injections, Laser Coagulation, Macular Edema, Male, Middle Aged, Questionnaires, Retina, Retreatment, Sickness Impact Profile, Time Factors, Treatment Outcome, Visual Acuity",

author = "Ursula Schmidt-Erfurth and Lang, {Gabriele E} and Holz, {Frank G} and Schlingemann, {Reinier O} and Paolo Lanzetta and Pascale Massin and Ortrud Gerstner and Bouazza, {Abdelkader Si} and Haige Shen and Aaron Osborne and Paul Mitchell",

year = "2014",

month = may,

doi = "10.1016/j.ophtha.2013.11.041",

language = "English",

volume = "121",

pages = "1045--53",

journal = "Ophthalmology",

issn = "0161-6420",

publisher = "Elsevier Inc.",

number = "5",

}

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

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

SN - 0161-6420

VL - 121

SP - 1045

EP - 1053

JO - Ophthalmology

JF - Ophthalmology

IS - 5

ER -

Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study

Abstract

Keywords

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