Subgroup Analysis of the MARINA Study of Ranibizumab in Neovascular Age-Related Macular Degeneration

doi:10.1016/j.ophtha.2006.10.045

Ophthalmology

Volume 114, Issue 2, February 2007, Pages 246-252

https://doi.org/10.1016/j.ophtha.2006.10.045 Get rights and content

Objective

An examination of clinically relevant subgroups of patients in the MARINA study of ranibizumab in treatment of minimally classic or occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) was done. Objectives were to determine the effectiveness of ranibizumab across subgroups, compare the effectiveness of ranibizumab with that of sham injection within subgroups, and evaluate the relationship between selected baseline characteristics and visual acuity (VA) outcomes.

Design

Retrospective subgroup analyses of 24-month data from the MARINA study.

Participants and Controls

Seven hundred sixteen patients were randomly assigned to 0.3 mg ranibizumab (n = 238), 0.5 mg ranibizumab (n = 240), or sham treatment (n = 238).

Methods

Efficacy outcomes were compared across subgroups based on patients’ gender, age, baseline VA score, baseline CNV lesion size, CNV lesion type, and duration of neovascular AMD using univariate analyses. Multivariate analyses were performed on the change from baseline to 24 months in VA score to assess further the correlation between baseline characteristics and VA outcome.

Main Outcome Measures

Proportion of patients losing <15 letters from baseline, proportion gaining ≥15 letters from baseline, and mean VA score change from baseline.

Results

For each of the 3 VA end points, all subgroups of ranibizumab-treated patients did better on average than the sham-treated patients. Increasing age, larger CNV lesion size at baseline, and a higher baseline VA score were all associated with greater loss of letters in the sham group or less gain of letters in the ranibizumab groups. However, the net benefit of ranibizumab versus sham treatment was greater in patients who scored higher than in those who scored lower in baseline VA.

Conclusions

This subgroup analysis of 24-month data from the MARINA study indicates that ranibizumab treatment was associated with an average increase from baseline VA in all subgroups evaluated, and that ranibizumab treatment was superior to sham treatment across all subgroups. The most important predictors of VA outcomes were, in decreasing order of importance, baseline VA score, CNV lesion size, and age.

Section snippets

Materials and Methods

MARINA was a 2-year, prospective, multicenter (96 sites), randomized, double-masked, sham-injection–controlled study of the safety, tolerability, and efficacy of monthly intravitreal injections of ranibizumab in patients with minimally classic or occult with no classic CNV secondary to AMD. The prespecified primary efficacy analysis was at 12 months, but monthly efficacy assessments continued through 24 months. Institutional review board approval of the study protocol was obtained before

Results

A total of 716 patients were enrolled and randomly assigned to treatment between March and December 2003. The randomized groups were well balanced for demographic characteristics (Table 1) and ocular characteristics in the study eye (Table 2) at baseline. In each group, approximately two thirds of the patients were female, and 96% to 97% of patients were white. The mean age in each group was 77 years. The mean ± standard deviation VA score (number of letters read) at baseline was 53.6±14.1,

Discussion

The MARINA study in patients with minimally classic or occult with no classic CNV was the first to demonstrate that a treatment for neovascular AMD could preserve and also improve VA. On average, these effects were sustained over a 2-year treatment period.⁵ Our retrospective, exploratory analysis of clinically relevant subgroups of patients from the MARINA study indicates that ranibizumab treatment for 24 months was consistently superior to sham treatment in all subgroups examined—gender, CNV

Acknowledgments

The authors acknowledge Steven Butler, PhD, and Carol Y. Chung, PhD, for expert statistical advice and Robert Y. Kim, MD, for clinical scientific advice and review.

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We conducted a single-center, retrospective, case-control cohort study in Belgium.
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Our study failed to demonstrate an effect of smoking on the short-term treatment response to anti-VEGF in nAMD.
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Nous avons mené une étude de cohorte cas-témoins, monocentrique et rétrospective en Belgique.
Cent quarante-sept yeux de 131 patients, dont 92 femmes (70 %) ont été traités par IVT d’anti-VEGF. L’âge moyen au moment de la première IVT était de 79 ± 9 ans. Dix-sept patients (13 %) étaient des fumeurs actifs au moment des IVT. En moyenne, ils étaient 11 ans plus jeunes que les non-fumeurs. Ils présentaient plus souvent du liquide sous-rétinien (94 % contre 65 %). Les analyses de Mann-Whitney comparant le changement de l’épaisseur maculaire centrale et le changement d’acuité visuelle en logarithme de l’angle minimum de résolution entre les deux groupes n’ont montré aucune différence significative. En comparant la réponse au traitement entre les patients ayant fumé moins de 10 paquets-années (PA) (y compris les non-fumeurs) et les patients ayant fumé plus de 10 PA, aucune différence significative n’a été trouvée. Dans un modèle de régression logistique binaire, les hommes répondaient moins bien aux IVT d’anti-VEGF que les femmes, avec un odds ratio de 0,27 pour une bonne réponse. C’était le seul prédicteur statistiquement significatif de réponse au traitement.
Notre étude n’a pas démontré d’effet du tabagisme sur la réponse à court terme au traitement anti-VEGF dans la DMLAn.
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To investigate the anatomical and visual outcomes of the patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (anti-VEGF), according to the baseline best-corrected visual acuity (BCVA) based on the multicenter real-life data.
Five-hundred-ninety patients who had taken the Pro Re Nata (PRN) treatment regimen with three loading doses and at least one year of follow-up were included. The patients were divided into three groups according to the baseline BCVA: Group 1 (BCVA ≥ 1.3 Logmar), Group 2 (1.3 Logmar > BCVA ≥ 0.3 Logmar), and Group 3 (BCVA ≤ 0.2 Logmar). BCVA, central macular thickness (CMT), and the number of injections and visits were evaluated.
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Seventy-three nAMD patients (73 eyes) treated with anti-VEGF agents for 12 months using the pro re nata regimen were included in this retrospective longitudinal study. Patients were split into 3 groups according to the time from diagnosis to first anti-VEGF injection: < 48 h (group 1); 48 h-7 days (group 2); > 7 days (group 3). Decimal best-corrected visual acuity (VA) and macular thickness (MT) were recorded at baseline and 1–2-, 3–4-, 6- and 12-month later. Furthermore, age, gender as well as the applied treatment and number of injections after 12 months of treatment were also registered and compared.
Long-term effect of the treatment demonstrated enhanced VA in group 1 patients compared with the rest of groups after 1–2-, 6-, and 12-month follow-up (P < 0.05). Positive effects of early treatment were additionally corroborated by the augmented percentage of patients with normal VA in the group 1 respect to the rest of groups over studied time points (P < 0.05). Moreover, the VA gain in nAMD at group 1 was obtained with a mean of 3.7 intravitreal injections over 1-year follow-up period. Regarding MT, non-significant difference was observed among groups.
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Manuscript no. 2006-1033.

Supported financially by Genentech, Inc. and Novartis Pharma AG, Basel, Switzerland.

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Original ArticleSubgroup Analysis of the MARINA Study of Ranibizumab in Neovascular Age-Related Macular Degeneration

Objective

Design

Participants and Controls

Methods

Main Outcome Measures

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

Acknowledgments

Am J Ophthalmol

Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes

Invest Ophthalmol Vis Sci

Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor

Invest Ophthalmol Vis Sci

Original Article
Subgroup Analysis of the MARINA Study of Ranibizumab in Neovascular Age-Related Macular Degeneration