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Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration.
Ophthalmology 2013; 120(5):1046-56O

Abstract

OBJECTIVE

To evaluate the 12-month efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered monthly and on an as-needed (PRN) basis in treatment-naïve patients with subfoveal neovascular age-related macular degeneration (wet AMD).

DESIGN

A 24-month, phase III, randomized, multicenter, double-masked, dose-response study.

PARTICIPANTS

Patients aged ≥ 50 years with subfoveal wet AMD.

METHODS

Patients (n = 1098) were randomized to receive ranibizumab 0.5 mg or 2.0 mg intravitreal injections administered monthly or on a PRN basis after 3 monthly loading doses.

MAIN OUTCOME MEASURES

The primary efficacy end point was the mean change from baseline in best-corrected visual acuity (BCVA) at month 12. Key secondary end points included the mean number of ranibizumab injections, the mean change from baseline in central foveal thickness (CFT) over time, and the proportion of patients who gained ≥ 15 letters of BCVA. Unless otherwise specified, end point analyses were performed using the last-observation-carried-forward method to impute missing data.

RESULTS

At month 12, the mean change from baseline in BCVA for the 4 groups was +10.1 letters (0.5 mg monthly), +8.2 letters (0.5 mg PRN), +9.2 letters (2.0 mg monthly), and +8.6 letters (2.0 mg PRN). The proportion of patients who gained ≥ 15 letters from baseline at month 12 in the 4 groups was 34.5%, 30.2%, 36.1%, and 33.0%, respectively. The mean change from baseline in CFT at month 12 in the 4 groups was -172.0 μm, -161.2 μm, -163.3 μm, and -172.4 μm, respectively. The mean number of injections was 7.7 and 6.9 for the 0.5-mg PRN and 2.0-mg PRN groups, respectively. Ocular and systemic safety profiles were consistent with previous ranibizumab trials in AMD and comparable between groups.

CONCLUSIONS

At month 12, the ranibizumab 2.0 mg monthly group did not meet the prespecified superiority comparison and the ranibizumab 0.5 mg and 2.0 mg PRN groups did not meet the prespecified noninferiority (NI) comparison. However, all treatment groups demonstrated clinically meaningful visual improvement (+8.2 to +10.1 letters) and improved anatomic outcomes, with the PRN groups requiring approximately 4 fewer injections (6.9-7.7) than the monthly groups (11.2-11.3). No new safety events were observed despite a 4-fold dose escalation in the study. The pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvasculaR age-related macular degeneration (HARBOR) study confirmed that ranibizumab 0.5 mg dosed monthly provides optimum results in patients with wet AMD.

FINANCIAL DISCLOSURE(S)

Proprietary or commercial disclosure may be found after the references.

Authors+Show Affiliations

Tennessee Retina, Nashville, Tennessee 37203, USA. bgbusbee@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23352196

Citation

Busbee, Brandon G., et al. "Twelve-month Efficacy and Safety of 0.5 Mg or 2.0 Mg Ranibizumab in Patients With Subfoveal Neovascular Age-related Macular Degeneration." Ophthalmology, vol. 120, no. 5, 2013, pp. 1046-56.
Busbee BG, Ho AC, Brown DM, et al. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology. 2013;120(5):1046-56.
Busbee, B. G., Ho, A. C., Brown, D. M., Heier, J. S., Suñer, I. J., Li, Z., ... Lai, P. (2013). Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology, 120(5), pp. 1046-56. doi:10.1016/j.ophtha.2012.10.014.
Busbee BG, et al. Twelve-month Efficacy and Safety of 0.5 Mg or 2.0 Mg Ranibizumab in Patients With Subfoveal Neovascular Age-related Macular Degeneration. Ophthalmology. 2013;120(5):1046-56. PubMed PMID: 23352196.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. AU - Busbee,Brandon G, AU - Ho,Allen C, AU - Brown,David M, AU - Heier,Jeffrey S, AU - Suñer,Ivan J, AU - Li,Zhengrong, AU - Rubio,Roman G, AU - Lai,Phillip, AU - ,, Y1 - 2013/01/23/ PY - 2012/03/30/received PY - 2012/09/26/revised PY - 2012/10/04/accepted PY - 2013/1/29/entrez PY - 2013/1/29/pubmed PY - 2013/6/26/medline SP - 1046 EP - 56 JF - Ophthalmology JO - Ophthalmology VL - 120 IS - 5 N2 - OBJECTIVE: To evaluate the 12-month efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered monthly and on an as-needed (PRN) basis in treatment-naïve patients with subfoveal neovascular age-related macular degeneration (wet AMD). DESIGN: A 24-month, phase III, randomized, multicenter, double-masked, dose-response study. PARTICIPANTS: Patients aged ≥ 50 years with subfoveal wet AMD. METHODS: Patients (n = 1098) were randomized to receive ranibizumab 0.5 mg or 2.0 mg intravitreal injections administered monthly or on a PRN basis after 3 monthly loading doses. MAIN OUTCOME MEASURES: The primary efficacy end point was the mean change from baseline in best-corrected visual acuity (BCVA) at month 12. Key secondary end points included the mean number of ranibizumab injections, the mean change from baseline in central foveal thickness (CFT) over time, and the proportion of patients who gained ≥ 15 letters of BCVA. Unless otherwise specified, end point analyses were performed using the last-observation-carried-forward method to impute missing data. RESULTS: At month 12, the mean change from baseline in BCVA for the 4 groups was +10.1 letters (0.5 mg monthly), +8.2 letters (0.5 mg PRN), +9.2 letters (2.0 mg monthly), and +8.6 letters (2.0 mg PRN). The proportion of patients who gained ≥ 15 letters from baseline at month 12 in the 4 groups was 34.5%, 30.2%, 36.1%, and 33.0%, respectively. The mean change from baseline in CFT at month 12 in the 4 groups was -172.0 μm, -161.2 μm, -163.3 μm, and -172.4 μm, respectively. The mean number of injections was 7.7 and 6.9 for the 0.5-mg PRN and 2.0-mg PRN groups, respectively. Ocular and systemic safety profiles were consistent with previous ranibizumab trials in AMD and comparable between groups. CONCLUSIONS: At month 12, the ranibizumab 2.0 mg monthly group did not meet the prespecified superiority comparison and the ranibizumab 0.5 mg and 2.0 mg PRN groups did not meet the prespecified noninferiority (NI) comparison. However, all treatment groups demonstrated clinically meaningful visual improvement (+8.2 to +10.1 letters) and improved anatomic outcomes, with the PRN groups requiring approximately 4 fewer injections (6.9-7.7) than the monthly groups (11.2-11.3). No new safety events were observed despite a 4-fold dose escalation in the study. The pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvasculaR age-related macular degeneration (HARBOR) study confirmed that ranibizumab 0.5 mg dosed monthly provides optimum results in patients with wet AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. SN - 1549-4713 UR - https://www.unboundmedicine.com/medline/citation/23352196/Twelve_month_efficacy_and_safety_of_0_5_mg_or_2_0_mg_ranibizumab_in_patients_with_subfoveal_neovascular_age_related_macular_degeneration_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-6420(12)00986-4 DB - PRIME DP - Unbound Medicine ER -