Article Date: 1/1/2007

GUEST EDITORIAL

Raise Your Hand Only If You're Sure
Clinical studies on efficacy and safety should continue to guide treatment decisions.

By Jennifer I. Lim, MD
 
Jennifer I. Lim, MD, is associate professor of ophthalmology at the University of Southern California Keck School of Medicine in Los Angeles and is the medical director for clinical trials at Doheny Eye Institute. Dr. Lim is a member of Genentech�s advisory board and speakers� bureau, and has received research grants from the company.

Informal polls at major retinal meetings suggest that the current utilization of non-FDA approved medications for the treatment of choroidal neovascularization (CNV) in age-related macular degeneration (AMD) patients rivals the use of FDA-approved treatments.1 We are at a truly interesting period in the management of AMD patients with CNV.
 
Unlike the past decade, when treatments were unlikely to improve visual acuity (VA), retinal specialists now have at least 2 treatments that can offer patients potentially significant VA improvement. One of these, ranibizumab (Lucentis, Genentech), has been studied extensively in randomized phase 3 clinical trials and has been shown to be both effective and safe.2,3 The other drug, bevacizumab (Avastin, Genentech), has been used off-label and has been found in clinical practices throughout the country to be effective and not associated with significant or frequent side effects.4-6 However, we do not know whether one drug is better than the other, and if so, by what degree. Nor do we truly know that the safety profile of bevacizumab equals that of ranibizumab.
 
In several recent retina meetings, informal polls have shown that almost every retina specialist has used bevacizumab in the management of their AMD patients with CNV. More interestingly, a large proportion of retinal specialists continue to use bevacizumab even after ranibizumab has been approved by the FDA and after Medicare has agreed to cover the cost of its use. Such widespread use in the latter scenario suggests that the clinical experiences of some retina specialists leads them to believe bevacizumab is efficacious and safe. This perception is indeed powerful and may have an impact on other retina specialists who have no experience with either drug.
 
More Data Required
It is my opinion, however, that until a full, unbiased evaluation of both drugs is performed, perception cannot be taken to equal reality. We have witnessed the phenomenon in medicine when a drug was felt to be safe and was later linked to significant side effects. This is why post-marketing drug surveillance is important for ranibizumab and why formal efficacy and safety studies of bevacizumab are needed. To that end, the National Eye Institute is sponsoring a phase 3 comparison trial of ranibizumab and bevacizumab for treatment of AMD patients with CNV (Comparison of Age-related Macular Degeneration Treatments Trials [CATT]). The CATT study will hopefully determine the extent to which these 2 drugs are equivalent in efficacy and safety.
 
I urge retinal physicians to enroll their patients in the CATT study. For those who believe the drugs are equivalent, the premise of the clinical trial should be appealing. For those who are uncertain about the safety profile of bevacizumab as compared to ranibizumab, this study will determine that safety profile. We must remember not to jump on the bandwagon of new treatments and to maintain our objectivity and scientific perspectives. 
 
References
1. ASRS 2006 preferences and trends membership survey. 8th annual PAT survey. Presented at the American Society of Retina Specialists 24th Annual Meeting; September 9-13, 2006; Cannes, France.
2. Rosenfeld PJ, Brown DM, Heier JS, et al; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419-1431.
3. Brown DM, Kaiser PK, Michels M, et al; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432-1444.
4. Spaide RF, Laud K, Fine HF, et al. Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration. Retina. 2006;26:383-390.
5. Bashshur ZF, Bazarbachi A, Schakal A, Haddad ZA, El Haibi CP, Noureddin BN. Intravitreal bevacizumab for the management of choroidal neovascularization in age-related macular degeneration. Am J Ophthalmol. 2006;142:1-9.
6. Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology. 2006;113:363-372.

 



Retinal Physician, Issue: January 2007