Download Health-Related Quality of Life and Health Economics Associated

Clinical Overview of
Age-Related Macular Degeneration
Victor H. Gonzalez, MD
Medical Director
Valley Retina Institute
McAllen, TX
Age-Related Macular Degeneration




Affects patients ≥ 50 years of age
Caucasian race, cigarette smoking, obesity, and
hypertension are significant risk factors
Condition marked by the appearance of drusen, an
accumulation of apparently undigested products of
retinal pigment epithelial cells under the basal lamina of
Bruch's membrane
Progressive deterioration of Bruch’s membrane, the
retinal pigment epithelium, choriocapillaris, and outer
retina in the macular area
Age-Related Macular Degeneration (AMD)



Leading cause of severe vision loss in the developed
countries
– Marked by
 Decreased visual acuity and contrast sensitivity
 Metamorphopsia and scotoma
2 forms
– Non-neovascular (dry)
– Neovascular (exudative, or “wet”)
90% of severe vision loss results from wet AMD
Vingerling JR. Epidemiol Rev. 1995;17:347.
Hyman L. Age Related Macular Degeneration: Principles and Practice. New York: Raven Press; 1992;1-32.
Age-Related Macular Degeneration (AMD)
Advanced AMD (choroidal neovascularization
or central GA) currently affects approximately
1.4 million people in the United States.
• ~ 8 million Americans at high risk for
developing advanced AMD
• Potential increase in cases to 3 million by
year 2020
GA = Geographic atrophy.
Friedman DS, et al. Arch Ophthalmol. 2004;122:564-572.
Bressler NM, et al. Arch Ophthalmol. 2003:121:1621-1624.
Drusen and AMD—Progression
Drusen
RPE Atrophy
Dry AMD
RPE & Sensory Detachment
Hemorrhagic Detachment
Fibrous Disciform Scar
Exudative AMD
RPE = retinal pigment epithelium.
Jack J. Kanski, Jay Menon. Clinical Ophthalmology: A Systematic Approach. Elsevier Science; 2003.
How Is AMD Detected?



Clinical exam
Visual function measurement
– Visual acuity
– Amsler grid
– Contrast sensitivity
Diagnostic procedures
– Fluorescein angiography
– Optical coherence
tomography
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
1
2
2
1. http://images.google.com/images?q=Amsler+grid+%2B+AMD&ndsp=20&svnum=10&hl=en&lr=&client=firefoxa&rls=org.mozilla:en-US:official_s&start=0&sa=N
2. Image courtesy of Dr. V. Gonzalez, Valley Retina Institute P.A.
Interventions to Slow Progression
• AREDS formulation
–
–
–
–
–
Vitamin C 500 mg
Vitamin E 400 IU (400 mg)
Beta-carotene 15 mg (28640 IU vitamin A)
Zinc oxide 80 mg
Cupric oxide 2 mg
• Principal finding of study
– Antioxidant vitamin/mineral (zinc) supplements modestly
reduced risk of progression and
vision loss over 6 years vs placebo
AREDS = Age-Related Eye Disease Study.
AREDS Research Group. Arch Ophthalmol. 2001;119:1417.
AREDS Summary

Early AMD
– No benefit from supplements

Intermediate AMD/monocular
advanced AMD
– Antioxidants plus zinc or zinc
alone significantly reduced the risk
of developing advanced AMD

An estimated 300,000 Americans
could avoid developing advanced
AMD over 5 years by taking
AREDS-type supplements
AREDS Research Group. Arch Ophthalmol. 2001;119:1417.
Wet AMD



Less common than dry
AMD, but more serious
90% of severe vision loss
results from wet AMD
Metamorphopsia is the initial
symptom. Most lesions are
not visible clinically
Hyman L. Age Related Macular Degeneration: Principles and Practice. New York: Raven Press; 1992.
Image courtesy of Dr. V. Gonzalez, Valley Retina Institute P.A.
Treatments for Wet AMD
• Thermal laser coagulation1
•
•
– MPS: Macular Photocoagulation Study
Photodynamic therapy with verteporfin
– TAP: Treatment of Age-Related Macular Degeneration with
Photodynamic therapy2
– VIP: Verteporfin in Photodynamic therapy3
Anti-VEGF therapies
– Pegaptanib sodium
 VISION: VEGF Inhibition Study in Ocular Neovascularization4
– Ranibizumab (Lucentis)
 ANCHOR Trial5  MARINA Trial6  FOCUS Trial7
– Bevacizumab (Off-label)8
1. Macular Photocoagulation Study Group. Arch Ophthalmol. 1994;112:500. 2. (TAP) Study Group. Arch Ophthalmol. 1999;
117:1329. 3. VIP Study Group. Am J Ophthalmol. 2001;131:541. 4. Gonzales CR. Retina. 2005;25:815. 5. ANCHOR Study
Group. Invest Ophthalmol Vis Sci. 2006;47:E-Abstract 2963. 6. MARINA Study Group. Invest Ophthalmol Vis Sci. 2006; 47:EAbstract 2959. 7. http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=9147.
8.
http://www.fda.gov/CDER/foi/label/2004/125085lbl.pdf#search=%22Avastin%20package%20insert%22.
Laser Photocoagulation




Obliterates choroidal neovascularization (CNV),
preventing further growth of fibrovascular tissue
For some patients, it remains the 1st-line therapy for
well demarcated extrafoveal/juxtafoveal CNV lesions
50% chance of recurrence within 2 years of treatment
May damage surrounding tissue
Macular Photocoagulation Study Group. Arch Ophthalmol. 1991;109:1220.
Fine SL, et al. N Engl J Med. 2000;342:483.
Photodynamic Therapy with Verteporfin
Photodynamic therapy
 Rapid closure of vessels
 Intra- and extracellular infiltration of
inflammatory cells
 Increased edema in the short term
 Transient antiangiogenic effects
 Upregulates vascular endothelial growth factor
 90% of patients need retreatment at 3 months
Schmidt-Erfurth U, et al. Invest Ophthalmol Vis Sci. 2002;43:830.
Photodynamic Therapy Studies


TAP Study1
– Multicenter, double-blind, placebo-controlled, randomized,
clinical trial of verteporfin vs placebo
– AMD with classic subfoveal lesions
– Significant benefit with PDT therapy at 12 and 24 months
VIP Study2
– Occult or minimally classic
– By month 24, verteporfin group was less likely to have
moderate to severe vision loss
TAP = Treatment of age-related macular degeneration with photodynamic therapy; PDT = photodynamic therapy;
VIP = Verteporfin In photodynamic therapy
1. TAP Study Group. Arch Ophthalmol. 1999;117:1329.
2. VIP Study Group. Am J Ophthalmol. 2001;131:541.
Vascular Endothelial Growth Factor1
• A protein that regulates angiogenesis (normal and
abnormal)
• Member of a family of angiogenic and lymphangiogenic
growth factors
• Secreted by a variety of cells in response to
hypoxia/ischemia and other signals
• Many strategies now target this factor2
– Interfering with pro-angiogenic growth factors, receptors, or
downstream signaling
– Upregulating endogenous inhibitors, or administering
exogenous inhibitors
– Directly targeting neovasculature
1. Adamis AP, et al. Retina. 2005;25:111.
2. Witmer AN, et al. Prog Retin Eye Res. 2003;22:1.
Pegaptanib—Anti-VEGF Aptamer
Selective VEGF inhibition

Binds selectively to VEGF165
–
Pathologic isoform

Spares normal vasculature

Mechanisms of action
–
Antiangiogenic2
–
Antipermeable2
–
Antiinflammatory3
Pegaptanib
1
Pegaptanib
binds to VEGF165
VEGF = vascular endothelial growth factor
1. http://www.revophth.com/index.asp?page=1_652.htm. 2. Ishida S, et al. J Exp Med. 2003;198:483.
3. Carrasquillo KG , et al. Invest Ophthalmol Vis Sci. 2003;44(1):290.
VEGF Inhibition Study in Ocular
Neovascularization (VISION)




Two randomized controlled studies involving 1186
patients in 117 centers
Intravitreal injections every 6 weeks for 1 year
Primary endpoint: % of patients losing
<15 letters at 1 year
Mean letters of visual acuity loss: 8 in pegaptanibtreated vs 15 in placebo at 1 year
Gragoudas ES. N Engl J Med. 2004;351:2805.
VISION Study
Primary efficacy endpoint:
% of patients losing <15 letters at week 54
0.3 mg
1 mg
3 mg
Sham
N = 294 N = 300 N = 296 N = 296
< 15 letters
P-value
70%
71%
65%
55%
< .0001
.0003
.0310
—
Adapted with permission from Gragoudas ES. N Engl J Med. 2004;351:2805. Copyright © 2004
Massachusetts Medical Society. All rights reserved.
Ranibizumab



Humanized fragment of a
monoclonal antibody
Targets all isoforms of VEGF
3 randomized clinical trials
(ANCHOR, MARINA, and
FOCUS)
Ranibizumab
Genentech, Inc. Data on file.
Ranibizumab
ANCHOR Trial




423 patients with predominantly classic CNV
randomized to
– PDT/sham injection Q 3 mo for 2 years
– Placebo PDT/0.3 mg ranibizumab injection once
per month
– Placebo PDT/0.5 mg ranibizumab injection once
per month1
Primary endpoint: % of patients losing <15 letters
in 1 year1
Endpoint reached by 94% and 96% of patients
Vision improved in 36% – 40% of patients2
CNV = choroidal neovascularization; PDT = photodynamic therapy
1. Kaiser PK. Ophthalmology. 2005;9(1).
2. http://www.clinicaltrials.gov/ct/show/NCT00061594?order=3.
Ranibizumab
MARINA Trial



716 patients with minimally classic or occult lesions
Patients randomized to monthly injections with 0.3
mg or 0.5 mg ranibizumab, or sham
Therapy found to improve vision in patients with
wet AMD
Association for Research in Vision and Ophthalmology. ARVO2006. 2006.
MARINA Year 1 Results
and Conclusions





95% of ranibizumab subjects lost <15 letters
(vs 62% of sham)
25% – 34% of ranibizumab subjects gained ≥15 letters
(vs 5% of sham)
First phase III clinical trial to show improvement in mean
visual acuity
No serious ocular side effects
No apparent systemic safety concerns
Association for Research in Vision and Ophthalmology. ARVO2006. 2006.
Bevacizumab
(Off-Label)




Recombinant humanized monoclonal antibody that
binds VEGF
First anti-VEGF medication FDA approved as
treatment for metastatic colorectal cancer
Not approved for ophthalmic use
Demonstrated efficacy in 2 case series (50 and 79
patients)1,2
1. Rich RM, et al. Retina. 2006;26:495.
2. Avery RL, et al. Ophthalmology. 2006;113:363.
AMD Summary



AREDS formulation significantly reduces the risk of
progression from intermediate to advanced AMD1
Pegaptanib sodium provides a safe treatment for all
lesion compositions2
Recently approved ranibizumab is the first drug to
improve visual acuity in 30% – 40% of patients3
1. AREDS Research Group. AREDS report no. 8. Arch Ophthalmol. 2001;119:1417.
2. D’Amico DJ, et al. Clinical Trial Group. Ophthalmology. 2006;113:1001.
3. Heier JS, et al. Ophthalmology. 2006;113:642.
Treatment Summary


Early data suggest that anti-VEGF treatment alone
may not be a long-term solution
Numerous other antiangiogenic and/or antiinflammatory agents offer hope for the future
– Bevacizumab
– siRNAs
– Anecortave acetate
– Squalamine lactate
– Triamcinolone acetonide
– Kinase inhibitors
– VEGF trap
– AdPEDF
The Goals of Treating AMD
• To minimize loss of visual acuity and central vision
• To preserve reading ability with/without visual aids
• To optimize quality of life
• To minimize adverse effects of treatment modalities
We look forward to the next decade of AMD
management, as investigations on
antiangiogenesis, inflammation, and other
strategies continue.
Health-Related Quality of Life and
Health Economics Associated with
AMD
Glenda S. Owens, RPh, MHA, CDM
Vice President
Pharmacy Services
Arcadian Health Plan
San Dimas, California
Burden of Age-Related Macular Degeneration
(AMD) and Visual Impairment
 AMD
is the most common cause of severe, irreversible
vision loss
 An estimated 200,000 new cases of wet AMD are
diagnosed each year in the United States
 Without treatment, most patients rapidly progress to
legal blindness (20/200) in less than 2 years
 The impact of visual impairment on direct and indirect
costs and on patients’ health-related quality of life is
significant
1. National Institutes of Health: National Eye Institute. Vision Problems in the U.S. 2002;20. Available at:
http://catalog.nei.nih.gov/productcart/pc/viewPrd.asp?idcategory=43&idproduct=47. Accessed July 31, 2006.
2. Foundation of the American Academy of Ophthalmology. AMD: An Overview of the Disease. Available at:
http://www.faao.org/what/AMD/Overview.cfm. Accessed July 31, 2006.
Impact of Visual Impairment on Annual Direct
and Indirect Costs

In the United States, annual direct medical costs associated with
visual impairment totaled $48.7 billion in 2003.1

When all indirect costs such as lost productivity are factored in,
the total annual cost was $67.6 billion.1

Loss of vision among elderly women increases the risk of
frequent falls.2

In 2003 more than 1.8 million seniors age 65 years and older
were treated in emergency departments for fall-related injuries
and more than 421,000 were hospitalized.3
1. NIH National Eye Institute Hu Analysis, available at: http://www.nei.nih.gov/eyedata/hu_estimates.asp#table2.
Accessed July 31, 2006.
2. Coleman AL, et al. Ophthalmology. 2004;111:857.
3. CDC.2005. Available at http://www.cdc.gov/ncipc/factsheets/falls.htm. Accessed July 31, 2006.
Patient Reported Visual Function (PRVF)


Importance of PRVF1
– Visual acuity (VA) is the standard visual measurement used in clinical trials.
However, VA does not equal visual function or the patient perspective of the
impact of vision problems on function
The National Eye Institute Visual Function Questionnaire
(NEI VFQ-25) is the measurement tool for self-reported visual function2
– Assesses vision-targeted functioning
 Measures impact of vision problems on function for many common eye
conditions
– Represents the patient perspective of the impact of vision problems on
function with attention to
 Near activities
 Distance activities
 Vision-related dependency
1. Presented at ARVO. April 30–May 4, 2006, Fl.
2. Mangione CM, et al. Arch Ophthalmol. 2001;119:1050
What Are Patient-Reported Outcomes
(PROs)?





Patient self-reported assessment of the impact of their health status on
– Quality of life
– Ability to function
PRO data are widely accepted in oncology, medicine, orthopedics,
rehabilitation, etc
Use of PROs in ophthalmology reveal the patient’s belief about their level
of visual function, which may not be reflective of their visual acuity (VA)
VA is the standard visual measurement used in clinical trials; however, VA
does not equal visual function
PROs complement VA data
Visual Acuity Does Not Equal Visual Function
These 2 patients have the same VA; however,
visual function is markedly different
Genentech Data on file. Reprinted with permission.
Visual Acuity Does Not Equal Visual Function
Despite normal VA, there is a temporary tilt in
vision early after translocation surgery, but this tilt
is corrected by the second stage of the eye
muscle surgery.
Images of grandfather clocks © Copyright 2006, Duke University Eye Center. Reprinted with permission.
NEI VFQ-25
Administration and Scoring

Administration
– Most patients can complete the questionnaire in 10
minutes
– Conducted in-person, by telephone interview, or it
can be self-administered

Scoring system (overall and subscales)
– Scores range from 0 (worst) to 100 (best) for visionrelated functions
Mangione CM, et al. Arch Ophthalmol. 2001;119:1050.
NEI VFQ-25 Subscales
Subscale
Number of Items
Description of Items
General vision
1
• 6-level health rating item
General health
1
• 5-level health rating item
Near vision
6
•
•
•
•
•
•
Distance vision
6
• Going out to movies/plays/sports events
• Going downstairs in dim light or at night
• Reading street signs or names of stores
Reading normal newsprint
Seeing well up close
Finding objects on crowded shelf
Reading small print ( telephone book, Rx)
Figuring out whether bills are accurate
Shaving, hair styling, putting on makeup
• Taking part in sports or active activities
• Seeing and enjoying programs on tv
• Recognizing people you know across a room
Vision-specific
dependency
3
• Need much help from others
• Stay home most of time
• Rely too much on others’ word
Mangione CM, et al. Arch Ophthalmol. 2001;119:1050.
NEI VFQ-25 Subscales
Subscale
Number of Items
Description of Items
Driving
3
• Difficulty driving in familiar places during the day
• Difficulty driving in familiar places during the
night
• Difficult conditions (ie, bad weather, rush hour)
Peripheral vision
1
• Noticing objects off to the side
Color vision
1
• Difficulty matching clothes
Ocular pain
2
• Amount pain
• Amount time: pain
Vision-specific
role difficulties
2
• Accomplish less
• Limited in endurance
Vision-specific
social function
2
• Seeing how people react
• Visiting others
Vision-specific
mental health
4
•
•
•
•
Amount true of frustration
Amount true of embarrassment
Amount true of no control
Amount time of worry
Mangione CM, et al. Arch Ophthalmol. 2001;119:1050.
How Do We Interpret Changes in the
NEI VFQ-25?


SST Report No. 1 1
– A 3-line loss was associated with a 10-point decrease in the
NEI VFQ-25
AREDS Report No. 142
– Changes in NEI VFQ-25 overall and subscale scores of 10
points or more associated with
 Clinically significant changes in vision (≥15 letter change)
 Progression to advanced AMD from intermediate stage of
AMD
1. Miskala PH, et al. Arch Ophthalmol. 2004;122:758.
2. Lindblad AS, Clemons TE. Arch Ophthalmol. 2005;123:1207.
Improvement in Near Activities
Mean Change in VFQ Score
Placebo (n = 238)
12
10
8
6
4
2
0
-2
-4
-6
-8
-10
-12
Ranibizumab 0.3 mg (n = 238)
0
1
2
3
4
5
6
Ranibizumab 0.5 mg (n = 240)
7
8
9 10 11 12
Months
P values vs placebo:
0.3 mg—.0457 at month 1; .0045 at month 2; <.0001 at months 3, 6, 9, and 12.
0.5 mg—.0413 at month 1; .0305 at month 2; <.0001 at months 3, 6, 9, and 12.
Presented at ARVO. April 30–May 4, 2006, Fl.
Improvement in Distance Activities
Mean Change in VFQ Score
Placebo (n = 238)
12
10
8
6
4
2
0
-2
-4
-6
-8
-10
-12
Ranibizumab 0.3 mg (n = 238)
0
1
2
3
4
5
6
Ranibizumab 0.5 mg (n = 240)
7
8
Months
P values vs placebo:
0.3 mg—.0067 at month 1; <.0001 at months 2, 3, 6, 9, and 12.
0.5 mg—>.05 at month 1; .0127 at month 2; <.0001 at months 3, 6, 9, and 12.
Presented at ARVO. April 30–May 4, 2006, Fl.
9 10 11 12
Improvement in Vision-Specific
Dependency
Mean Change in VFQ Score
Placebo (n = 238)
12
10
8
6
4
2
0
-2
-4
-6
-8
-10
-12
Ranibizumab 0.3 mg (n = 238)
0
1
2
3
4
5
6
7
Ranibizumab 0.5 mg (n = 240)
8
9 10 11 12
Months
P values vs placebo:
0.3 mg—>.05 at month 1; .0094 at month 2; .0063 at month 3; .0051 at month 6; .0011 at month 9;
.0004 at month 12.
0.5 mg—>.05 at month 1; <.0197 at month 2; .0012 at month 3; <.0001 at months 6, 9, and 12.
Presented at ARVO. April 30–May 4, 2006, Fl.
MARINA PRVF Conclusions
Ranibizumab-treated subjects reported improvements in
visual function in almost all VFQ subscales at month 12
 Ranibizumab-treated subjects reported clinically
meaningful improvements in the VFQ subscales most
important in AMD
– Near activities
– Distance activities
– Vision-specific dependency

Chang TS, et al. Presented at ARVO. April 30–May 4, 2006, Fl. (Poster 5252/B667)
Key Ocular Serious Adverse Events
MARINA
ANCHOR
Ranibizumab
Ranibizumab
Placebo
(n = 236)
0.3 mg
(n = 238)
0.5 mg
(n = 239)
PDT
(n = 143)
0.3 mg
(n = 137)
0.5 mg
(n = 140)
Presumed endophthalmitis
Culture positive
Culture negative
Culture not done
0
0
0
0
0
1 (0.4%)
0
2 (0.8%)*
0
0
0
0
0
0
0
1 (0.7%)
0
1 (0.7%)†
Uveitis
0
2 (0.8%)
1 (0.4%)‡
0
0
1 (0.7%)†
Rhegmatogenous retinal
detachment
0
0
0
1(0.7%)‡
1(0.7%)
0
Retinal tear
0
1 (0.4%)
1 (0.4%)
0
0
0
Vitreous hemorrhage
0
1 (0.4%)
1 (0.4%)
0
1 (0.7%)
0
Lens damage
0
0
1 (0.4%)
0
0
0
case reported as uveitis by investigator; †Same subject had 2 episodes each reported as uveitis, received
systemic antibiotics once; ‡Same subject had 2 episodes.
PDT = photodynamic therapy.
*1
Presented at ARVO. April 30–May 4, 2006, FL.
Key Systemic Adverse Events
MARINA
ANCHOR
Ranibizumab
Ranibizumab
Placebo
(n = 236)
0.3 mg
(n = 238)
0.5 mg
(n = 239)
PDT
(n = 143)
0.3 mg
(n = 137)
0.5 mg
(n = 140)
23 (9.7%)
20 (8.4%)
20 (8.4%)
12 (8.4%)
3 (2.2%)
9 (6.4%)
-2/-2
-1/-2
-4/-1
0/0.3
-2/-2
-2/1
Myocardial
infarction
1 (0.4%)
1 (0.4%)
1 (0.4%)
1 (0.7%)
1 (0.7%)
3 (2.1%)
Cerebrovascular accident
1 (0.4%)
1 (0.4%)
3 (1.3%)
1 (0.7%)
1 (0.7%)
1 (0.7%)
0
1 (0.4%)†
2 (0.8%)‡
2 (1.3%)§
3 (2.2%)**
2 (1.4%)††
Hypertension (HTN)*
Mean change in SBP/DBP (mmHg)
Key arterial
thromboembolic events
Death
*No serious adverse events of HTN reported during year 1; †Myocardial infarction; ‡Small bowel
infarct, chronic asthma/chronic obstructive pulmonary disease (COPD); §Cardiac arrest, COPD;
**Cardiac arrest, respiratory arrest, viral syndrome; ††Cardiac failure, chronic heart failure.
Presented at ARVO. April 30–May 4, 2006, FL.
VISION Study—Safety


No apparent drug-related SAEs
Few injection-related SAEs
(n = 7545 total intravitreal injections)
n
% per
Injection
% per
Patient/y
Endophthalmitis*
12
0.16
0.1
Lens damage/cataract
5
0.07
0.1
Retinal detachment
6
0.08
0
Events
SAEs = serious adverse events.
Adapted with permission from Gragoudas ES, et al. N Engl J Med. 2004;351:2805.
Copyright © 2004 Massachusetts Medical Society. All rights reserved.
Do We See a Change in VisionRelated QOL in the MARINA Trial?
Secondary Endpoint
Mean Change in Visual Acuity Over Time
Placebo (n = 238)
Ranibizumab 0.3 mg (n = 238)
Ranibizumab 0.5 mg (n = 240)
10
No. ETDRS Letters
8
+7.2
+6.5
6
4
17.7 letter
difference*
2
0
-2
1
2
3
4
5
6
7
8
9
10
11
12
17.0 letter
difference*
-4
-6
-8
-10
Month
*P < .0001 vs placebo
Presented at ARVO. April 30–May 4, 2006, Fl.
-10.5
Mean Change in VFQ Score from Baseline at
Month 12
Placebo (n = 238)
Ranibizumab 0.3 mg (n = 238)
Ranibizumab 0.5 mg (n = 240)
Improvement
15
10
(P < .0001)
(P < .0001)
(P < .0001)
(P < .0001)
VFQ score
5
0
-5
-10
-15
Overall
visual
function
Near
activities
Distance
activities
Visionspecific
dependency
Decline
Baseline = 0; P-values for combined 0.3 and 0.5 mg ranibizumab vs placebo.
Error bars represent the 95% confidence interval of the mean.
Chang TS, et al. Presented at ARVO. April 30–May 4, 2006, Fl. (Poster 5252/B667)
Mean Change in VFQ Score from Baseline at
Month 12
Improvement
VFQ 25 Score
15
(P < .0001)
(P < .0001)
10
Placebo (n = 238)
Ranibizumab 0.3 mg (n = 238)
Ranibizumab 0.5 mg (n = 240)
(P < .0001)
(P < .0001)
5
0
-5
-10
-15
Decline
General
vision
Visionspecific
social
function
Visionspecific
mental
health
Visionspecific
role
difficulties
Baseline = 0; P-values for combined 0.3 and 0.5 mg ranibizumab vs placebo.
Error bars represent the 95% confidence interval of the mean.
Presented at ARVO. April 30–May 4, 2006.
Mean Change in VFQ Score from Baseline at
Month 12
Improvement
Placebo (n = 238)
Ranibizumab 0.3 mg (n = 238)
Ranibizumab 0.5 mg (n = 240)
VFQ 25 Score
15
10
(P = .260)
5
(P < .0001)
(P = .125)
(P = .051)
0
-5
-10
-15
Driving
General
health
Ocular
pain
Decline
Baseline = 0; P-values for combined 0.3 and 0.5 mg ranibizumab vs placebo.
Error bars represent the 95% confidence interval of the mean.
Presented at ARVO. April 30–May 4, 2006.
Color
vision
Health Economics
Cost to Society vs Benefits of Treatment


Blindness has a significant impact
– Annual medical expenditures
– Indirect costs approximately 10 x direct costs
Benefits of treatment
– Continuation or resumption of normal daily living activities,
including driving
– Avoid secondary medical problems, such as broken bones
due to falls
– Minimal caregiver responsibilities
– Decreased likelihood of nursing home admission
Implications for the Managed Care
Community
Stuart Levine, MD, MHA
Assistant Clinical Professor/Internal Medicine
University of California, Los Angeles
David Geffen School of Medicine
Chief Medical Officer
Prospect Medical
Los Angeles, California
Age-Related Macular Degeneration (AMD)
Who Will Be Covered?




Medicare advantage
Medicare part D
Medicaid
Commercial
– Pharmacy benefit
– Medical benefit
AMD
Priorities

Is it a priority of the health plan?

Is it a priority of the physician community?

Is it a priority for patients?
– Quality of life
– Ability to function
AMD
Cost of AMD on the Health Plan
Direct costs
 Hospital
 Physician
 Pharmacy
AMD
Cost of AMD on the Health Plan
Indirect costs
 Disability
 Long-term care
 Patient adherence for all illnesses
 Caregiver burden
AMD
Prevention




Zinc
Vitamin C and E
Beta carotene
Cupric oxide
AMD
What Current Therapies Are Covered?



Thermal laser coagulation
PDT with verteporfin
Anti-VEGF
–
On-Label use


–
Pegaptanib sodium
Ranibizumab
Off-Label use

Bevacizumab*
*Covered by Medicare in some states.
AMD
Future Therapies
How do you decide on future therapies?






Efficacy
Medication vs placebo
Head-to-head medication trials
Cost
Cost efficacy/medical cost offset
Pharmacoeconomics
AMD
What Data Will Be Required?
Clinical Trials Must Demonstrate Efficacy of a Medication in
Treatment of AMD






Types of trials
Length of trials
Placebo controlled
Head-to-head
Numbers of patients
Statistical significance
AMD
Patient Population Targeted



Medicare
Medicaid age, blind, and disabled
Dually eligible — Medicare - Medicaid
AMD
Will Occult AMD Be Covered?
At what degree of disease will the patient
be eligible for treatment?


Visual acuity
Disability
Cataract removal model of criteria