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The relative clinical effectiveness of ranibizumab and bevacizumab in diabetic macular oedema: an indirect comparison in a systematic review

BMJ 2012; 345 doi: https://doi.org/10.1136/bmj.e5182 (Published 13 August 2012) Cite this as: BMJ 2012;345:e5182
  1. John A Ford, research assistant1,
  2. Andrew Elders, statistician1,
  3. Deepson Shyangdan, research fellow2,
  4. Pamela Royle, senior research fellow2,
  5. Norman Waugh, professor of public health medicine and health technology assessment2
  1. 1Health Services Research Unit, University of Aberdeen, Health Services Building, Aberdeen AB25 2ZD, UK
  2. 2Warwick Evidence, Division of Health Sciences, Warwick Medical School, Coventry, UK
  1. Correspondence to: J A Ford john.ford{at}uea.ac.uk
  • Accepted 16 July 2012

Abstract

Objective To indirectly compare the effectiveness of ranibizumab and bevacizumab in the treatment of diabetic macular oedema.

Design Systematic review and indirect comparison.

Data sources Medline (1996–September 2011), Embase (1996–September 2011), and the Cochrane Central Register of Controlled Trials (Issue 4, 2011).

Selection criteria for studies Randomised trials evaluating ranibizumab or bevacizumab in diabetic macular oedema with a common comparator and sufficient methodological similarity to be included within an indirect comparison were eligible for inclusion.

Main outcome measures The primary outcome was the proportion of patients with an improvement in best corrected visual acuity of more than two lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Secondary outcomes included mean changes in best corrected visual acuity and in central macular thickness, and adverse events. Best corrected visual acuity was converted to logMAR units, a linear scale of visual acuity with positive values representing increasing visual loss. Indirect comparisons were done using Bayesian methods to estimate relative treatment effects of bevacizumab and ranibizumab.

Results Five randomised controlled trials with follow-up of 6–12 months and a common comparator (multiple laser treatment) were sufficiently similar to be included in the indirect comparison. Generally studies were small, resulting in wide credible intervals. The proportions of patients with an improvement in best corrected visual acuity of >2 lines were 21/77 participants (27%) for bevacizumab and 60/152 participants (39%) for ranibizumab (odds ratio 0.95 (95% credible interval 0.23 to 4.32)). The wide credible intervals cannot exclude a greater improvement, or worse outcome, for either drug. The mean change in best corrected visual acuity non-significantly favoured bevacizumab (treatment effect −0.08 logMAR units (−0.19 to 0.04)). The difference in mean change in central macular thickness was not statistically significant between ranibizumab and bevacizumab (treatment effect −6.9 μm (−88.5 to 65.4)).

Conclusions Results suggest no difference in effectiveness between bevacizumab and ranibizumab, but the wide credible intervals cannot exclude the possibility that either drug might be superior. Sufficiently powered, direct head to head trials are needed.

Footnotes

  • We thank the study authors who provided additional information: Wen Xing, Catey Bunce, and Michel Michaelides for the BOLT study; Peter Campochiaro and Afsheen Khwaja for READ-2; Mehdi Yaseri and Masoud Soheilian for Soheilian et al. We also thank Graeme MacLennan, Health Services Research Unit, University of Aberdeen, for his statistical advice.

  • Contributors: All authors contributed to the design, interpretation, and writing of the manuscript and approved the final manuscript. PR carried out the searches. JAF, DS, and PR screened titles and extracted data. AE carried out the indirect comparison. JAF is the guarantor. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding: No external funding required.

  • All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: the authors had support from University of Aberdeen and Warwick University for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; JAF, DS, PR and NW have undertaken an Evidence Review Group report for NICE on ranibizumab for diabetic macular oedema, which may be relevant to the submitted work.

  • Ethical approval: Not required

  • Protocol: No protocol exists for this study. The study arose out of a single technology appraisal for NICE.

  • Data sharing: Further details available in the ERG report on the NICE website (www.nice.org.uk/nicemedia/live/13125/53408/53408.pdf).

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