The relative clinical effectiveness of ranibizumab and bevacizumab in diabetic macular oedema: an indirect comparison in a systematic review.
OBJECTIVE
To indirectly compare the effectiveness of ranibizumab and bevacizumab in the treatment of diabetic macular oedema.


METHODS
Systematic review and indirect comparison.


METHODS
Medline (1996-September 2011), Embase (1996-September 2011), and the Cochrane Central Register of Controlled Trials (Issue 4, 2011).


METHODS
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.


METHODS
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.
Health Services Research Unit, University of Aberdeen, Health Services Building, Aberdeen AB25 2ZD, UK. john.ford@uea.ac.uk
John A
JA
Ford
Andrew
A
Elders
Deepson
D
Shyangdan
Pamela
P
Royle
Norman
N
Waugh
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001499:Bayes Theorem; D000068258:Bevacizumab; D003930:Diabetic Retinopathy / Q000150:complications*; D006801:Humans; D008269:Macular Edema / Q000188:drug therapy* / Q000209:etiology; D008390:Markov Chains; D009010:Monte Carlo Method; D000069579:Ranibizumab; D016896:Treatment Outcome; D014792:Visual Acuity
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000069579:Ranibizumab