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Research

Bevacizumab for neovascular age related macular degeneration (ABC Trial): multicentre randomised double masked study

BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c2459 (Published 10 June 2010) Cite this as: BMJ 2010;340:c2459
  1. Adnan Tufail, consultant ophthalmologist, medical retina department1,
  2. Praveen J Patel, locum consultant ophthalmologist1,
  3. Catherine Egan, consultant ophthalmologist1,
  4. Philip Hykin, consultant ophthalmologist1,
  5. Lyndon da Cruz, consultant ophthalmologist1,
  6. Zdenek Gregor, consultant ophthalmologist1,
  7. Jonathan Dowler, consultant ophthalmologist1,
  8. Mohammed A Majid, consultant ophthalmologist2,
  9. Clare Bailey, consultant ophthalmologist2,
  10. Quresh Mohamed, consultant ophthalmologist3,
  11. Robert Johnston, consultant ophthalmologist3,
  12. Catey Bunce, senior statistician, research and development department1,
  13. Wen Xing, statistician, research and development department1,
  14. ABC Trial Investigators
  1. 1Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD
  2. 2Bristol Eye Hospital, Bristol, BSL 2LX
  3. 3Gloucestershire Eye Department, Cheltenham General Hospital, Cheltenham GL53 7AN
  1. Correspondence to: A Tufail adnan.tufail{at}moorfields.nhs.uk
  • Accepted 15 April 2010

Abstract

Objectives To evaluate the efficacy and safety of intravitreous bevacizumab injections for the treatment of neovascular age related macular degeneration.

Design Prospective, double masked, multicentre, randomised controlled trial.

Setting Three ophthalmology centres in the United Kingdom.

Participants 131 patients (mean age 81) with wet age related macular degeneration randomised 1:1 to intervention or control.

Interventions Intravitreous bevacizumab (1.25 mg, three loading injections at six week intervals followed by further treatment if required at six week intervals) or standard treatment available at the start of the trial (photodynamic treatment with verteporfin for predominantly classic type neovascular age related macular degeneration, or intravitreal pegaptanib or sham treatment for occult or minimally classic type neovascular age related macular degeneration).

Main outcome measures Primary outcome: proportion of patients gaining ≥15 letters of visual acuity at one year (54 weeks). Secondary outcomes: proportion of patients with stable vision and mean change in visual acuity.

Results Of the 131 patients enrolled in the trial, five patients did not complete the study because of adverse events, loss to follow-up, or death. In the bevacizumab group, 21 (32%) patients gained 15 or more letters from baseline visual acuity compared with two (3%) in the standard care group (P<0.001); the estimated adjusted odds ratio was 18.1 (95% confidence interval 3.6 to 91.2) and the number needed to treat was 4 (3 to 6). In addition, the proportion of patients who lost fewer than 15 letters of visual acuity from baseline was significantly greater among those receiving bevacizumab treatment (91% (59) v 67% (44) in standard care group; P<0.001). Mean visual acuity increased by 7.0 letters in the bevacizumab group with a median of seven injections compared with a decrease of 9.4 letters in the standard care group (P<0.001), and the initial improvement at week 18 (plus 6.6 letters) was sustained to week 54. Among 65 patients treated with bevacizumab, there were no cases of endophthalmitis or serious uveitis related to the intervention. All end points with respect to visual acuity in the study eye at 54 weeks favoured bevacizumab treatment over standard care.

Conclusions Bevacizumab 1.25 mg intavitreous injections given as part of a six weekly variable retreatment regimen is superior to standard care (pegaptanib sodium, verteporfin, sham), with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 54 weeks.

Trial registration number Current controlled trials ISRCTN83325075

Footnotes

  • Trial investigators: Adnan Tufail (chief investigator); Laura Henderson, Ola Segun-Odumosu (trial managers).

  • Co-investigators: Praveen J Patel (principal investigator), Catherine Egan, Philip Hykin, Zdenek Gregor, Jonathan Dowler (Moorfields); Mohammed Majid (principal investigator), Clare Bailey (Bristol); Quresh Mohamed (principal investigator), Robert Johnston (Cheltenham).

  • Recruitment support: Richard Andrews, Andrew Webster.

  • Data management: Richard Seeberan, Catey Bunce, Wen Xing.

  • Statistical analysis: Catey Bunce, Wen Xing.

  • Pharmacy/drug management: Jagdev Bains and Moorfields Pharmacy; Moorfields Pharmaceuticals prepared bevacizumab for intraocular use.

  • Staff in clinical trials unit: Kerry Waller, Felicia Ikeji, Matthew Richardson, Kanom Bibi.

  • Optometry: Dan Ehrlich, Catherine Grigg, Sonal Rughani, Jen Smith, Shima Shah, Mina Devani, Graham Brown, Rebecca Black.

  • Treating doctors: Sobha Sivaprasad, Andrew Browning, Yvonne D’Souza, Nachi Acharya, Andrew Kaines, Sam Fraser-Bell, Maria Niskopolou, Noel Horgan, Fred K Chen, Waheeda Rahman, Rajen Gupta, Richard Hanson, Tariq Aslam, Mohammed Musadiq, Tryfon Rotsos, Gayatri Banerjee.

  • Image acquisition: Matthew Richardson, Kulwant Sehmi, Richard Poynter.

  • Image reading centre: Network of Reading Centres, UK: Usha Chakravarthy, Simon Harding, Nicola Duff, Alison Murphy, Liam Patton, Tunde Peto, Vittorio Silvestri.

  • Data and safety monitoring committee: Marion Campbell (chair), Frank Holz, Robyn Guymer.

  • Steering committee: Astrid Fletcher (chair), Catey Bunce, Praveen J Patel, Adnan Tufail, Richard Wormald.

  • Contributors: AT and PJP were responsible for the study concept and design, with additional input from CE. PJP, CE, LDC, ZG, JD, CB, QM, and RJ contributed to recruitment of patients, data collection, and manuscript review, CB, WX, AT, and PJP undertook analysis and interpretation of the data, AT and PJP drafted the manuscript. AT, PJP, CB, and WX had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the analysis. AT and PJP are guarantors.

  • Funding: This study was funded by the special trustees of Moorfields Eye Hospital. We also received financial support from the Department of Health through an award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. Additional local support was obtained from the National Eye Research Centre, Bristol.

  • Role of funding source: The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

  • Competing interests: AT has been on advisory boards for Novartis, Pfizer, GSK, MSD, Allergan. PJP has received travel grants from Novartis. CE has been on advisory boards for Novartis, Pfizer, Allergan. PH has been on advisory boards for Novartis. MM has received travel grants from Novartis. CB has received research grants for investigator sponsored trials, travel grants, and lecture fees from Novartis. RJ has received money for speaking engagements from Novartis, and is a shareholder of a software company that has business links with Novartis and Pfizer. The pharmaceutical division at Moorfields (Moorfields Pharmaceuticals) is involved in the repackaging of bevacizumab for intraocular use for sale to other institutions. The authors who work at Moorfields Eye Hospital have no financial gain from this endeavour, and no patents or patent applications with regard bevacizumab are owned by the authors or Moorfields Pharmaceuticals.

  • Ethical approval: This study was approved by the ethics committees of all clinical centres. Patients provided written informed consent for study participation.

  • Data sharing: No additional data available.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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