September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Dose-response analysis of ranibizumab as-needed regimens for best-corrected visual acuity improvement in patients with diabetic macular edema using a modeling approach
Author Affiliations & Notes
  • Yuan Xiong
    Novartis Pharmaceutical Corporation, East Hanover, New Jersey, United States
  • Etienne Pigeolet
    Noavartis Pharma AG, Basel, Switzerland
  • Philippe Margaron
    Noavartis Pharma AG, Basel, Switzerland
  • Amy Racine
    Noavartis Pharma AG, Basel, Switzerland
  • Footnotes
    Commercial Relationships   Yuan Xiong, Novartis Pharmaceutical Corporation (E); Etienne Pigeolet, Novartis Pharma AG (E); Philippe Margaron, Novartis Pharma AG (E); Amy Racine, Novartis Pharma AG (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2102. doi:
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      Yuan Xiong, Etienne Pigeolet, Philippe Margaron, Amy Racine; Dose-response analysis of ranibizumab as-needed regimens for best-corrected visual acuity improvement in patients with diabetic macular edema using a modeling approach. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2102.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Ranibizumab (RBZ) 0.5 mg pro re nata (PRN) has a well-established efficacy profile and is approved for treatment of diabetic macular edema (DME) in >100 countries worldwide. The Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol T study compared the efficacy of RBZ 0.3 mg PRN with other anti-vascular endothelial growth factor agents; this dosing regimen is neither studied previously nor approved. We assessed the dose responses of RBZ using a step-wise modeling approach for better understanding of the Protocol T 12-month efficacy results.

Methods : Summary data from the randomized clinical trials (RCT) RESOLVE, RESTORE, REVEAL, RESPOND, RETAIN, RISE, RIDE, Protocol I, and Protocol T with relevant arms were included in the analyses. An exploratory analysis was performed to verify a dose-response signal, then a dose-response model was built to describe the relationship between the average monthly doses of RBZ and the mean best-corrected visual acuity (BCVA) change from baseline at Month 12. A similar analysis was performed in a subgroup of patients with baseline BCVA <69 letters from RESOLVE, RESTORE, REVEAL, RESPOND, RETAIN, and Protocol T studies.

Results : The pooled exploratory analysis indicated a linear dose-response a dose range within which the RBZ average monthly dose from Protocol T falls into (Figure 1). After accounting for inter-study variability (study design, retreatment algorithms, etc.), the dose-response model predicted that, in Protocol T, RBZ 0.5 mg PRN may have provided a median BCVA gain of 13 letters (approximately 2–3 letters more than RBZ 0.3 mg PRN) with a mean of 7–7.5 injections over 12 months (Figure 2). In the subgroup with baseline BCVA <69 letters, it was predicted that a mean of 9 RBZ 0.5 mg PRN injections may have led to a median BCVA gain of 19 letters.

Conclusions : The dose-response model suggested that, in Protocol T, RBZ 0.5 mg PRN may have led to higher BCVA gains compared with RBZ 0.3 mg PRN. It was predicted that, compared with RBZ 0.3 mg PRN, RBZ 0.5 mg PRN may have led to a BCVA gain of 2–3 letters more in the overall population and 4–5 letters in patients with baseline BCVA <69 letters.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

 

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