Elsevier

Ophthalmology

Volume 122, Issue 9, September 2015, Pages 1811-1819
Ophthalmology

Original article
Ranibizumab 0.5 mg for Diabetic Macular Edema with Bimonthly Monitoring after a Phase of Initial Treatment: 18-Month, Multicenter, Phase IIIB RELIGHT Study

Presented in part at: the Association for Vision and Research in Ophthalmology, May 5–9, 2013, Seattle, Washington; USA Eye Complications Study Group, May 23–25, 2013, Barcelona, Spain; and the World Ophthalmology Congress, April 2–6, 2014, Tokyo, Japan.
https://doi.org/10.1016/j.ophtha.2015.05.038Get rights and content

Purpose

To evaluate ranibizumab 0.5 mg using bimonthly monitoring and individualized re-treatment after monthly follow-up for 6 months in patients with visual impairment due to diabetic macular edema (DME).

Design

A phase IIIb, 18-month, prospective, open-label, multicenter, single-arm study in the United Kingdom.

Participants

Participants (N = 109) with visual impairment due to DME.

Methods

Participants received 3 initial monthly ranibizumab 0.5 mg injections (day 0 to month 2), followed by individualized best-corrected visual acuity (BCVA) and optical coherence tomography–guided re-treatment with monthly (months 3–5) and subsequent bimonthly follow-up (months 6–18). Laser was allowed after month 6.

Main Outcome Measures

Mean change in BCVA from baseline to month 12 (primary end point), mean change in BCVA and central retinal thickness (CRT) from baseline to month 18, gain of ≥10 and ≥15 letters, treatment exposure, and incidence of adverse events over 18 months.

Results

Of 109 participants, 100 (91.7%) and 99 (90.8%) completed the 12 and 18 months of the study, respectively. The mean age was 63.7 years, the mean duration of DME was 40 months, and 77.1% of the participants had received prior laser treatment (study eye). At baseline, mean BCVA was 62.9 letters, 20% of patients had a baseline BCVA of >73 letters, and mean baseline CRT was 418.1 μm, with 32% of patients having a baseline CRT <300 μm. The mean change in BCVA from baseline to month 6 was +6.6 letters (95% confidence interval [CI], 4.9–8.3), and after institution of bimonthly treatment the mean change in BCVA at month 12 was +4.8 letters (95% CI, 2.9–6.7; P < 0.001) and +6.5 letters (95% CI, 4.2–8.8) at month 18. The proportion of participants gaining ≥10 and ≥15 letters was 24.8% and 13.8% at month 12 and 34.9% and 19.3% at month 18, respectively. Participants received a mean of 6.8 and 8.5 injections over 12 and 18 months, respectively. No new ocular or nonocular safety findings were observed during the study.

Conclusions

The BCVA gain achieved in the initial 6-month treatment period was maintained with an additional 12 months of bimonthly ranibizumab PRN treatment.

Section snippets

Study Design

RELIGHT was an 18-month, prospective, open-label, multicenter, single-arm, phase III study of patients in the United Kingdom with visual impairment due to DME using a bimonthly follow-up and treatment protocol after a 6-month period of monthly monitoring. The study was conducted between January 2011 and April 2013 in accordance with the Declaration of Helsinki. The study protocol was reviewed and approved by a multicenter research ethics committee for each contributing center. Patients provided

Participant Disposition and Demographics

Of 109 enrolled participants, 100 (91.7%) and 99 (90.8%) completed 12 and 18 months of the study, respectively. The main reasons for discontinuation were AEs (3.7%), consent withdrawal, and loss to follow-up (1.8% each) (Fig 2). The efficacy and safety analyses were performed on the FAS and safety set, respectively, consisting of 109 participants. The mean age was 63.7 years, and the majority of participants were male (70.6%). Ninety-three participants (85.3%) were white patients, and 84.4% of

Discussion

The RELIGHT study demonstrated that 12 months of bimonthly PRN treatment with ranibizumab, after a treatment period of 3 initial doses followed by 3 monthly visits with PRN treatment, was able to maintain the initial mean VA improvements in participants with visual impairment due to DME. There were no new safety findings reported in this study.

With monthly monitoring from months 3 to 5 and bimonthly monitoring from months 6 to 18, plus PRN treatment, participants gained on average +4.8 letters

Acknowledgments

The authors thank Sabyasachi Ghosh and Aditi Gandhe (Global Business Services-Global Medical and Clinical Services, Novartis Healthcare Pvt. Ltd., Hyderabad, India) and Sue Lupton (Novartis Pharmaceuticals UK Ltd., Surrey, United Kingdom) for medical writing and editorial assistance toward the development of this article.

References (19)

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Supplemental material is available at www.aaojournal.org.

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

I.P.: Consultant for Allergan and Alimera; Consultant and lecturer − Novartis and Bayer.

S.B.: Received grants and personal fees − Novartis, Bayer, and Allergan (outside the submitted work).

B.J.L.B.: Financial support for attending conferences and worked as an advisor – Novartis; Personal fees − Bayer.

U.C.: Travel support for attendance at meetings and honoraria for attendance at advisory boards − Novartis, Roche, Allergan.

L.D.: Consultant – Novartis, Bayer, Allergan, Alcon, Alimera, Oraya and Thrombogenics; Travel grants- Novartis, Bayer, Allergan and Principal Investigator for Clincial Trials sponsored by Novartis and Allergan.

R.P.G.: Consultant and received educational grants − Novartis, and his institution performs clinical trials sponsored by Novartis.

J.G.: Consultant − Novartis Pharmaceuticals UK Ltd., Allergan Ltd., and Bayer PLC; received travel support and research funding − Novartis Pharmaceuticals UK Ltd.

S.P.: Consultant – Bayer, Novartis; Grant support – Novartis; Educational sponsorship to conferences − Allergan, Novartis, Alcon; Paid Speaker for Heidelberg Engineering in the year 2015.

S.S.: Research grants and travel grants, advisory board − Allergen, Bayer, Novartis, Roche.

C.A. and J.W.: Employees − Novartis Pharmaceuticals UK Ltd.

C.B.: Employee − Novartis Pharmaceuticals UK Ltd., when the manuscript was developed; currently is an employee of F. Hoffmann-La Roche Ltd., Basel, Switzerland.

The study was conducted in the United Kingdom and was funded and managed by Novartis Pharmaceutical UK and is registered with www.clinicaltrials.gov (NCT01257815).

Author Contributions:

Conception and design: Pearce, Banerjee, Burton, Chakravarthy, Downey, Gale, Gibson, Pagliarini, Patel, Sivaprasad, Andrews, Brittain, Warburton, RELIGHT Study Group

Data collection: Pearce, Banerjee, Burton, Chakravarthy, Downey, Gale, Gibson, Pagliarini, Patel, Sivaprasad, Andrews, Brittain, Warburton, RELIGHT Study Group

Analysis and interpretation: Pearce, Banerjee, Burton, Chakravarthy, Downey, Gale, Gibson, Pagliarini, Patel, Sivaprasad, Andrews, Brittain, Warburton, RELIGHT Study Group

Obtained funding: Not applicable

Overall responsibility: Pearce, Banerjee, Burton, Chakravarthy, Downey, Gale, Gibson, Pagliarini, Patel, Sivaprasad, Andrews, Brittain, Warburton, RELIGHT Study Group

Group members are listed online in Appendix 1 (available at www.aaojournal.org).

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