Comparing the effectiveness and costs of Bevacizumab to Ranibizumab in patients with Diabetic Macular Edema: a randomized clinical trial (the BRDME study)

Abstract

BackgroundThe effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials. For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date. However, if proved non-inferior to ranibizumab, use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity. A cost-effectiveness study has been designed to substantiate this hypothesis.AimTo compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema. It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness.DesignThis is a randomized, controlled, double masked, clinical trial in 246 patients in seven academic trial centres in The Netherlands.OutcomesThe primary outcome measure is the change in best-corrected visual acuity (BCVA) in the study eye from baseline to month 6. Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months, the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months, the number of adverse events in 6 months, and the costs per quality adjusted life-year of the two treatments.

Are the odds shifting against pharma in the fight for cheaper treatment for macular degeneration?

“…8 The Guernsey eye service also used only bevacizumab in 2015, which Lotery provided. 9 The GMC has confirmed that doctors practising there are registered with them.…”

Association of Circulating Markers With Outcome Parameters in the Bevacizumab and Ranibizumab in Diabetic Macular Edema Trial

“…15 The most relevant inclusion criteria for DME patients were (1) clinically significant macular edema as defined by the Early Treatment Diabetic Retinopathy Study (ETDRS); (2) central macula thickness of >325 lm as documented using optical coherence tomography (OCT); (3) no previous intravitreal anti-VEGF or triamcinolone injections within 3 months prior to randomization; (4) no previous macular focal laser therapy within 3 months of commencement of the study period; and (5) age >18 years old. The most relevant exclusion criteria were (1) presence of ocular disease other than DR and cataract; (2) uncontrolled glaucoma; (3) intraocular surgery, injection, or laser photocoagulation within 3 months of commencement of the study period; and (4) active untreated proliferative DR.…”

“…Blood samples of DME patients included in the ongoing BRDME study 15 were analyzed. The BRDME study was a large clinical trial in which patients with DME receive monthly antivascular endothelial growth factor (anti-VEGF) injections during 6 months in 7 university medical centers in the Netherlands (Dutch Trail Register NTR3247and ClinicalTrials.-gov NCT01635790).…”

“…[5][6][7][8] Other candidate biomarkers may be related to structural retinal damage in DR. These candidate biomarkers include mRNA levels of rhodopsin, iovs.arvojournals.org j ISSN: 1552-5783 RPE65, and retinoschisin and have been independently and significantly associated with disease progression of DR. [9][10][11][12][13][14] Using blood samples collected in the Bevacizumab to Ranibizumab in patients with Diabetic Macular Edema (BRDME) study, in which the effectiveness and costs of bevacizumab and ranibizumab are compared in patients with DME, 15 we explored the most strongly associated leads in DR biomarker research. In this prospective, multicenter study, we evaluated the diagnostic and prognostic value of mRNA of EPC markers CD34, CD133, and plasma mRNA of rhodopsin, RPE65, and retinoschisin in patients with DME.…”

Licence to save: a UK survey of anti-VEGF use for the eye in 2015

“…20 In Holland, bevacizumab is approved as first-line treatment for AMD, and a randomised trial to compare bevacizumab with ranibizumab for diabetic macular oedema is underway. 21 In Italy, Roche/Novartis were fined 180 million euros for trying to 'channel demand toward the much more expensive drug Lucentis, through an artificial distinction between the two products'. 22 To conclude, UK regulation has resulted in an unnecessarily expensive choice of anti-VEGF treatment, despite good evidence of safety, efficacy, cost savings, and support from the respected professional bodies for the use of bevacizumab, despite repeated requests to the Government.…”