Elsevier

Ophthalmology

Volume 120, Issue 1, January 2013, Pages 130-139
Ophthalmology

Original article
The SECURE Study: Long-Term Safety of Ranibizumab 0.5 mg in Neovascular Age-related Macular Degeneration

https://doi.org/10.1016/j.ophtha.2012.07.026Get rights and content

Objective

To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD).

Design

Twenty-four–month, open-label, multicenter, phase IV extension study.

Participants

Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study.

Methods

Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion).

Main Outcome Measures

Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections.

Results

Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline.

Conclusions

The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Study Design

SECURE was a 24-month, prospective, multicenter, phase IV, open-label extension study in patients with subfoveal CNV secondary to AMD who previously were treated for 1 year in either of the 2 ranibizumab studies EXCITE15 or SUSTAIN.16 The EXCITE and SUSTAIN studies were designed to assess the efficacy of alternate dosing regimens of ranibizumab. Thus, all patients received ranibizumab in the previous EXCITE (mean of approximately 5.5 ranibizumab injections in the quarterly treatment arms and

Patient Disposition and Demographics

A total of 134 of 353 EXCITE patients and 100 of 531 SUSTAIN patients who provided signed informed consent (n = 234) were enrolled in the SECURE study (Fig 1). The safety set consisted of 234 patients, and the FAS consisted of 233 patients (1 patient did not have a postbaseline VA assessment and was excluded from the FAS). Of the 234 enrolled patients, 210 (89.7%) completed the study (Table 1). The most common reasons for study discontinuation were AEs (3.4%), withdrawal of consent (3.4%), and

Discussion

The SECURE study was designed as a long-term extension study primarily to evaluate the safety of ranibizumab in patients who previously had been treated with ranibizumab for 1 year in the EXCITE or SUSTAIN studies. Results indicate that ranibizumab administered for 2 years of extension after 1 year of initial treatment was associated with a low incidence of ocular and nonocular AEs and SAEs. There were no new ocular or nonocular safety findings compared with the European Union SmPC18 for

Acknowledgments

The authors thank Sushmita Bhattacharya for assistance in developing the initial draft of the manuscript, Aditi Gandhe for medical writing and editorial support for the manuscript, and Mohammed Najeeb Ashraf for revision and resubmission support in all subsequent drafts of the manuscript, all from Medical Communications, Novartis Healthcare Private Ltd, Hyderabad, India. The authors also thank Martin Neuner-Jehle, Novartis Pharma AG, Basel, Switzerland, for coordinating the development of this

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    Manuscript no. 2011-1298.

    Appendix: 1 contains a list of the primary investigators who participated in this study (available at http://aaojournal.org).

    Financial Disclosure(s): The author(s) have made the following disclosure(s):

    Rufino Silva: Financial Support — International Advisory Board Member, Allergan, Pfizer, Novartis; THEA, Bayer.

    Bora Eldem: Financial support, advisory board - Novartis, Pfizer, Allergan, Bayer, and Bausch & Lomb.

    Robyn Guymer: Australian Advisory board — Novartis and Bayer.

    Margarita Gekkieva: Employee — Novartis Pharma AG Switzerland.

    Annette Nieweg: Employee — Novartis Pharma AG Switzerland.

    Stefan Pilz: Employee — Novartis Pharma AG Switzerland.

    Sponsored by Novartis Pharma AG, Basel, Switzerland, which participated in the design of the study; conducting the study; data collection; management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The study is registered with www.clinicaltrial.gov under number NCT00504959. Proprietary or commercial disclosure may be found after the references.

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