Ranibizumab versus Bevacizumab for the Treatment of neovascular macular degeneration: CATT study

Source: www.clinical-ophthalmology.com/index.php?option=com_content&view=article&id=52:ranibizumab-versus-bevacizumab-for-the-treatment-of-neovascular-macular-degeneration-catt-study-explained

CATT will be the first head-to-head trial of ranibizumab versus bevacizumab and is expected to return important safety and cost data

This study will be the largest head to head, Lucentis to Avastin trial so far. It appears to be a large, well-conducted RCT so is likely (in 2011) to answer some of the questions that hang over the two treatments.

Dr George A Williams (Beaumont Eye Institute, Royal Oak, Michigan, USA) gave an overview of the much-anticipated Comparison of AMD Treatment Trials (CATT) Study during a press conference at the 2008 AAO-SOE joint Congress.

Background

The health burden associated with advanced AMD is destined to rise as populations in the world's developed countries continue to age. The number of patients with either neovascular AMD or geographic atrophy is expected to have increased nearly 60% by 2020 compared with 2000.

The decrease in quality of life associated with AMD highlights the need for more effective treatment strategies, Dr Williams advised.

Existing agents

Vascular endothelial growth factor (VEGF) inhibitors hold the most promise in terms of AMD treatment he continued, and summarised the data on each as follows:

Ranibizumab (Lucentis) efficacy

25-40% of patients in studies experienced visual improvement.
more than 90% of patients experienced visual stabilisation.

Pegaptanib sodium (Macugen) / Photodynamic Therapy (PDT) efficacy

6-10% visual improvement.
70% of patients experienced visual stabilization.

Bevacizumab (Avastin)

FDA-approved for lung and colon cancer before ranibizumab was approved for AMD. Use in AMD is off-label.
initially used at cancer doses by intravenous infusion for treatment failures.
now given at much smaller doses by intraocular injection every 4-6 weeks.
small studies show apparent safety and efficacy, but has not been evaluated in randomised clinical trial settings.
no long-term follow-up has been reported.
systemic side-effects in patients with colon cancer include gastrointestinal perforations, haemorrhage, thromboembolic events, hypertension and proteinuria. Unknown relationship to intravitreal injections.

New challenges in the era of anti-VEGF therapy

Despite the potential that anti-VEGF agents hold for the treatment of neovascular AMD, there remain a number of obstacles and challenges that lie in the way of optimising their use. These include:

determination of optimal treatment schedule:
- monthly versus less frequent dosing schedule.
- treatment decisions based on clinical examination compared with decisions led by optical coherence tomography (OCT) or fluorescein angiographic (FA) images.
long-term safety of available anti-VEGF therapies:
- adverse event frequency beyond 2 years will require additional monitoring.
- Short- and long-term safety of bevacizumab largely unknown.

CATT, Dr Williams continued, may answer some of these questions.

The CATT study

CATT is a multi-centre randomised controlled trial designed assess the efficacy of ranibizumab compared with bevacizumab therapy for the treatment of neovascular AMD. CATT will be conducted in 44 clinical centers and is funded by the National Eye Institute.

Approximately 1200 participants aged 50 and older with subfoveal CNV secondary to AMD in at least one eye and visual acuity between 20/40 and 20/320 will take part in the study inclusive. The study eye must not have had any previous treatment for AMD. Patients will be randomised to one of 4 treatment arms:

ranibizumab: fixed-dosing schedule of every 4 weeks for 1 year; at 1 year, re-randomisation to ranibizumab every 4 weeks or to variable dosing.
bevacizumab: fixed-dosing schedule of every 4 weeks for 1 year; at 1 year, re-randomisation to bevacizumab every 4 weeks or to variable dosing.
ranibizumab: variable dosing for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
bevacizumab: variable dosing for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.

CATT participants will complete a total of 24 monthly study visits for 2 years. All CATT participants will receive a study treatment at their initial visit and will have monthly study visits thereafter for two years. Those who are assigned to the fixed monthly dosing groups will receive treatment at every visit. Those who are assigned to variable dosing groups will be evaluated for treatment at every visit. If lesion activity is present, the participant will receive a study treatment.

Study visit procedures include:

established tests of visual acuity conducted by examiners masked to the treatment assignment.
examination by a CATT ophthalmologist.
retinal photographs and OCTs assessed by masked graders in a centralised reading centers.

The primary outcome measurement of CATT will be mean change in visual acuity at 1 year. Secondary endpoints include:

number of treatments.
three-line change in visual acuity.
change in subretinal and intraretinal fluid on OCT.
change in lesion size on fluorescein angiography.
incidence of treatment complications (e.g. endophthalmitis, retinal detachment, cataract, and uveitis).
incidence of adverse events.
cost of treatments.

CATT is due to finish in February 2011.

Drug Costs

A pre-defined secondary endpoint of the study is cost of treatment. Cost is at the route of the off-label use of bevacizumab in neovascular AMD. In the USA, relative drug costs for the two agents are estimated at $45 for bevacizumab compared with $2030 for ranibizumab (a factor of 45 different).

"Would you treat your mother with a drug that has 40% the efficacy of another more expensive drug…60% the efficacy...80% the efficacy…?" Dr Williams asked. Evidence-based answers are needed to compare accurately both the efficacy and value of competing treatments, hopefully CATT will help advise on this matter, Dr Williams concluded.