Elsevier

Ophthalmology

Volume 118, Issue 5, May 2011, Pages 831-839
Ophthalmology

Original article
Efficacy and Safety of Monthly versus Quarterly Ranibizumab Treatment in Neovascular Age-related Macular Degeneration: The EXCITE Study

Presented at: EURETINA, May 14–17, 2009, Nice, France, and ARVO, May 3–7, 2009, Fort Lauderdale, Florida.
https://doi.org/10.1016/j.ophtha.2010.09.004Get rights and content

Objective

To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).

Design

A 12-month, multicenter, randomized, double-masked, active-controlled, phase IIIb study.

Participants

Patients with primary or recurrent subfoveal CNV secondary to AMD (353 patients), with predominantly classic, minimally classic, or occult (no classic component) lesions.

Intervention

Patients were randomized (1:1:1) to 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised of a loading phase (3 consecutive monthly injections) followed by a 9-month maintenance phase (either monthly or quarterly injection).

Main Outcome Measures

Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 12 and the incidence of adverse events (AEs).

Results

In the per-protocol population (293 patients), BCVA, measured by Early Treatment Diabetic Retinopathy Study-like charts, increased from baseline to month 12 by 4.9, 3.8, and 8.3 letters in the 0.3 mg quarterly (104 patients), 0.5 mg quarterly (88 patients), and 0.3 mg monthly (101 patients) dosing groups, respectively. Similar results were observed in the intent-to-treat (ITT) population (353 patients). The mean decrease in CRT from baseline to month 12 in the ITT population was −96.0 μm in 0.3 mg quarterly, −105.6 μm in 0.5 mg quarterly, and −105.3 μm in 0.3 mg monthly group. The most frequent ocular AEs were conjunctival hemorrhage (17.6%, pooled quarterly groups; 10.4%, monthly group) and eye pain (15.1%, pooled quarterly groups; 20.9%, monthly group). There were 9 ocular serious AEs and 3 deaths; 1 death was suspected to be study related (cerebral hemorrhage; 0.5 mg quarterly group). The incidences of key arteriothromboembolic events were low.

Conclusions

After 3 initial monthly ranibizumab injections, both monthly (0.3 mg) and quarterly (0.3 mg/0.5 mg) ranibizumab treatments maintained BCVA in patients with CNV secondary to AMD. At month 12, BCVA gain in the monthly regimen was higher than that of the quarterly regimens. The noninferiority of a quarterly regimen was not achieved with reference to 5.0 letters. The safety profile was similar to that reported in prior ranibizumab studies.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Study Design

The EXCITE study was a 1-year, randomized, double-masked, active-controlled, multicenter, Phase IIIb study in patients with subfoveal CNV secondary to AMD, comparing the efficacy and safety of quarterly dosing regimens of ranibizumab with a monthly dosing regimen during the maintenance phase, that is, from month 3 onward.

Eligible patients were randomly assigned in a 1:1:1 ratio to any of the following 3 double-masked treatment arms (Fig 1): loading doses of 3 initial monthly intravitreal

Patients

A total of 482 patients were screened and 353 patients were randomized for treatment with the study medication. As per the study design, patients received ranibizumab 0.3 mg quarterly (120 patients), ranibizumab 0.5 mg quarterly (118 patients), or ranibizumab 0.3 mg monthly dosing (115 patients). The PP population included 104 patients (86.7%) from the 0.3 mg quarterly, 88 (74.6%) from the 0.5 mg quarterly, and 101 (87.8%) from the 0.3 mg monthly dosing groups. The study was completed by 106

Discussion

The EXCITE trial is the first study directly comparing visual outcomes between monthly and quarterly dosing regimens in the treatment of patients with subfoveal CNV, secondary to AMD. The EXCITE study offers a rigorous analysis of the quarterly treatment regimen, with monthly study visits and OCT assessments, providing a monthly monitoring of functional and anatomic changes in the study eye. The EXCITE study allows to (1) compare the study outcome under monthly vs. quarterly treatment and (2)

Acknowledgments

The authors acknowledge medical writing assistance from Ajithkumar Vasudevan, PhD, and Shivani Mittra, PhD, Novartis Healthcare Pvt Ltd.

References (13)

There are more references available in the full text version of this article.

Cited by (0)

*Group members listed online in Appendix 1 (available at http://aaojournal.org).

Manuscript no. 2009-1732.

Financial Disclosure(s): The authors have made the following disclosures: Ursula Schmidt-Erfurth – Consultant – Alcon Laboratories Inc., Bayer Healthcare, Carl Zeiss Meditec, Heidelberg Engineering Inc., Novartis Pharmaceutical Corporation, Regeneron; Research Grant – Bayer Healthcare, Carl Zeiss Meditec, Novartis Pharmaceutical Corporation Bora Eldem – Lecture Fee, Financial Support for this project – Novartis Pharmaceuticals Corporation Robyn Guymer – Consultant – Novartis Pharmaceuticals Corporation Jean-Francois Korobelnik – Consultant –Alcon Laboratories, Bayer Healthcare, Novartis Pharmaceuticals Corporation, THEA Reinier Schlingemann – Consultant, Lecture Fee – Novartis Pharmaceuticals Corporation Peter Wiedemann – Lecture Fee – Novartis Pharmaceutical Corporation Christian Simader – Consultant – Novartis Pharmaceutical Corporation Margarita Gekkieva –Employee – Novartis Pharma Andreas Weichselberger –Employee – Novartis Pharma Supported by Novartis Pharma, AG, Switzerland.

A list of the primary investigators for the EXCITE study is available at http://aaojournal.org.

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