Korean J Ophthalmol.  2019 Apr;33(2):150-166. 10.3341/kjo.2018.0081.

Short-term Efficacy and Safety of Ranibizumab for Neovascular Age-related Macular Degeneration in the Real World: A Post-marketing Surveillance Study

• Woo SJ
• Cho GE
• Cho JH

• KMID: 2442620
• DOI: http://doi.org/10.3341/kjo.2018.0081

Abstract

PURPOSE
To investigate the short-term efficacy and safety of ranibizumab in the routine clinical setting in patients with neovascular age-related macular degeneration and to analyze the associated factors for visual outcome.
METHODS
This was a post-hoc analysis of a ranibizumab regulatory post-marketing surveillance study in which 4,136 patients were enrolled and followed for 12 weeks. Change in best-corrected visual acuity (BCVA), size of choroidal neovascularization, and the presence of hemorrhage and exudate were analyzed and the association between BCVA change and baseline characteristics were investigated. Data on ocular and systemic adverse events were collected.
RESULTS
Mean BCVA improved significantly and mean BCVA change was the logarithm of the minimal angle of resolution 0.13 ± 0.01 (p < 0.001). A lower baseline BCVA and younger age were significant predictive factors for visual improvement or maintenance (≥0 lines). For greater visual acuity gain (≥3 lines), no treatment history, lower baseline BCVA, younger age, and classic-type choroidal neovascularization were significant predictive factors. No new safety signals were found.
CONCLUSIONS
In this study, conducted in real-world clinical practice with a large number of neovascular age-related macular degeneration patients, visual and anatomical outcomes improved significantly after three monthly ranibizumab treatments. Treatment-naive patients had a higher chance of greater visual gain (≥3 lines) than non-naive patients.

Keyword

Efficacy; Age-related macular degeneration; Post marketing surveillance; Ranibizumab; Real-world evidence

MeSH Terms

Choroidal Neovascularization
Exudates and Transudates
Hemorrhage
Humans
Macular Degeneration*
Ranibizumab*
Visual Acuity
Ranibizumab

Figure

• 

  Fig. 1 Flow charts of grouping subjects enrolled in the ranibizumab regulatory post-marketing surveillance study. CRF = case report form; DME = diabetic macular edema; RVO = retinal vein occlusion; CNV = choroidal neovascularization; CSCR = central serous chorioretinopathy; SRNVM = subretinal neovascular membrane; BCVA = best-corrected visual acuity.

• 

  Fig. 2 Changes of best-corrected visual acuity after three monthly ranibizumab injections. (A) Best-corrected visual acuity (BCVA, mean ± standard deviation) of 2,811 subjects in the efficacy analysis set improved at three months from baseline (Wilcoxon signed rank test, p < 0.001). (B) Eyes of treatment-naive group achieved greater BCVA (mean ± standard error) gain compared to those of non-naive group (Wilcoxon rank sum test, p < 0.001). (C) Changes of BCVA were different among the three different choroidal neovascularization (CNV) groups (Kruskal-Wallis test, p < 0.001). logMAR = logarithm of minimum angle resolution.

• 

  Fig. 3 Proportion of patients with visual change categorized as logarithm of the minimum angle of resolution ≤−0.3 (Early Treatment Diabetic Retinopathy Study 3 or more lines gain); 0 to −0.3 (<3 lines gain or no change); 0.3 to 0 (<3 lines loss); and 0.3 (3 or more lines loss) in total, treatment-naive, and non-naive groups. The distribution of visual gain or loss was statistically different between the naive and non-naive groups (chi-square test, p < 0.001). BCVA = best-corrected visual acuity.

• 

  Fig. 4 Anatomical changes including choroidal neovascularization (CNV) size (A), retinal or subretinal hemorrhage (B), and exudate (C) after three monthly injections of ranibizumab on the total patients (n = 2,811) in the efficacy analysis set.

• 

  Fig. 5 Comparison of best-corrected visual acuity (BCVA) changes according to the age groups. (A) BCVA (mean ± standard error) improved in both <70 and ≥70 years age groups significantly from baseline (Wilcoxon signed rank test, both p < 0.001), however, the change is greater in the younger age group (Wilcoxon rank sum test, p < 0.001). (B) BCVA improved in all age groups (Wilcoxon signed rank test, p < 0.05) except for the oldest age group (p = 0.074) and the change in BCVA was different among the six age groups (Kruskal-Wallis test, p < 0.001). (C) BCVA change was correlated with age (r = 0.062, p = 0.001). logMAR = logarithm of minimum angle resolution.

• 

  Fig. 6 Comparison of best-correct visual acuity (BCVA) changes according to the baseline visual acuity. (A) BCVA (mean ± standard error) improved in both <20 / 100 and ≥20 / 100 groups significantly from baseline (Wilcoxon signed rank test, both p < 0.001) and the change was greater in the worse baseline visual acuity group (Wilcoxon rank sum test, p < 0.001). (B,C) BCVA improved in three baseline BCVA groups (Wilcoxon signed rank test, p < 0.05) but not for the group with the best baseline BCVA ( p = 0.351). The changes in BCVA were different among the four baseline BCVA groups (Kruskal-Wallis test, p < 0.001) and correlated with baseline BCVA (r = 0.331, p < 0.001). logMAR = logarithm of minimum angle resolution.

• 

  Fig. 7 Graphs showing baseline predictive factors associated with (A,B) a visual gain or no change from baseline best-corrected visual acuity (BCVA) and those associated with (C,D) a gain of 3 or more lines from baseline BCVA. (A) Age less than 70 years and baseline BCVA worse than 20 / 100 were the significant predictors for BCVA gain or no change (p = 0.083 and p < 0.001, respectively) in model 1. (B) In model 2, age group 40 to 49 years (p = 0.049) and baseline BCVA group <20 / 320, 20 / 320 to 20 / 100, 20 / 100 to 20 / 40 were the significant predictors for BCVA gain or no change. (C) No treatment history (p < 0.001), age less than 70 years (p < 0.001), baseline BCVA worse than 20 / 100 (p < 0.001), choroidal neovascularization (CNV) with predominantly classic CNV (p = 0.002), and minimally classic CNV (p = 0.017) were associated with BCVA gain of 3 or more lines. (D) In model 2, no prior treatment history (p < 0.001), age of 40 to 49 years (p = 0.004), baseline BCVA of <20 / 320, 20 / 320 to 20 / 100, 20 / 100 to 20 / 40 (all p < 0.001), predominantly classic CNV (p = 0.005), and minimally classic CNV (p = 0.024) were the significant predictors for BCVA gain of three or more lines. *Versus occult without classic CNV.

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