Raise Your Hand Only If You're Sure
Clinical studies on efficacy and safety should continue to guide treatment
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.
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.
4. Spaide RF, Laud K, Fine HF, et al. Intravitreal bevacizumab treatment of
choroidal neovascularization secondary to age-related macular degeneration.
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