The Systemic Safety of Ranibizumab in Patients 85 Years and Older with Neovascular Age-Related Macular Degeneration.

OBJECTIVE

Ranibizumab safety is well established for treatment of neovascular age-related macular degeneration (nAMD), but less is known about the risk of systemic serious adverse events (SAEs), specifically among patients with heightened baseline risk due to age (≥85 years). This analysis examines whether patients ≥85 years of age versus those <85 years experience an increased risk of key systemic SAEs during intravitreal ranibizumab treatment for nAMD.

DESIGN

Retrospective, pooled analysis of safety data from 5 phase III/IIIb multicenter randomized clinical trials in patients with nAMD: ANCHOR, MARINA, PIER, SAILOR, and HARBOR.

PARTICIPANTS

Patients with nAMD receiving ranibizumab (n = 4347) or control (sham/verteporfin photodynamic therapy, n = 441) treatment included in the safety-evaluable set of the 5 trials.

METHODS

The incidence of nonocular SAEs was analyzed stratified by age (<85 years [n = 3795] vs ≥85 years [n = 993]), treatment (control, ranibizumab 0.3 mg, ranibizumab 0.5 mg, ranibizumab 2.0 mg), and injection frequency (monthly, as needed [PRN]).

MAIN OUTCOME MEASURES

Incidence of key systemic SAEs, defined as total nonocular SAEs, deaths, cardiovascular events, cerebrovascular (CBV) events, and Antiplatelet Trialists' Collaboration events.

RESULTS

The MARINA and ANCHOR trials had greater rates of key SAEs for patients ≥85 years versus those <85 years. Ranibizumab exposure did not increase the risk of most SAEs in elderly patients; for CBV events and death, the effect of ranibizumab versus control treatment for age ≥85 years was not interpretable due to small number of events (CBV: n = 2, 2, 5 for control, ranibizumab 0.3 mg, and ranibizumab 0.5 mg, respectively; death: n = 2, 4, 5, respectively). Across all 5 trials, an increased risk was found for age ≥85 years versus <85 years for the marketed dose of ranibizumab 0.5 mg. In the HARBOR trial, increased rates of key SAEs (excluding total nonocular SAEs) for age ≥85 years versus <85 years were observed with monthly dosing but not with PRN dosing; event rates were similar for 2.0 mg versus 0.5 mg.

CONCLUSIONS

Consistent with general trends, the risk of key systemic SAEs was associated with age ≥85 years versus <85 years, but not with ranibizumab drug exposure. The difference between monthly versus PRN was inconclusive. There was no evidence of a dose effect. Interpretation of this retrospective analysis is limited because it was not prospectively powered for statistically definitive conclusions.