Ranibizumab and pegaptanib for the treatment of age-related macular degeneration

238 Pages·2008·1.16 MB·English

Health Technology Assessment 2008; Vol. 12: No. 16
Ranibizumab and pegaptanib for the
treatment of age-related macular
degeneration: a systematic review
and economic evaluation
JL Colquitt, J Jones, SC Tan, A Takeda, AJ Clegg
and A Price
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Ranibizumab and pegaptanib for the
treatment of age-related macular
degeneration: a systematic review
and economic evaluation
*
JL Colquitt, J Jones, SC Tan, A Takeda, AJ Clegg
and A Price
Southampton Health Technology Assessments Centre (SHTAC),
Wessex Institute for Health Research and Development (WIHRD),
University of Southampton, UK
* Corresponding author
Declared competing interests of authors: none
Published May 2008
This report should be referenced as follows:
Colquitt JL, Jones J, Tan SC, Takeda A, Clegg AJ, Price A. Ranibizumab and pegaptanib for
the treatment of age-related macular degeneration: a systematic review and economic
evaluation. Health Technol Assess 2008;12(16).
Health Technology Assessment is indexed and abstracted in Index Medicus/MEDLINE,
Excerpta Medica/EMBASE and Science Citation Index Expanded (SciSearch®) and
Current Contents®/Clinical Medicine.
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Health Technology Assessment 2008; Vol. 12: No. 16
Abstract
Ranibizumab and pegaptanib for the treatment of age-related
macular degeneration: a systematic review and economic
evaluation
*
JL Colquitt, J Jones, SC Tan, A Takeda, AJ Clegg and A Price
Southampton Health Technology Assessments Centre (SHTAC), Wessex Institute for Health Research and
Development (WIHRD), University of Southampton, UK
* Corresponding author
Objectives: To assess the clinical effectiveness and or more (a clinically important outcome having a
cost-effectiveness of ranibizumab and pegaptanib for significant impact on quality of life) was statistically
subfoveal choroidal neovascularisation (CNV) significantly greater in the pegaptanib group for doses
associated with wet age-related macular degeneration of 0.3 and 1.0 mg but not for 3.0 mg, and for all
(AMD). ranibizumab groups compared to the sham injection
Data sources: Electronic databases were searched groups or PDT. This was also statistically significant for
from inception to September 2006. Experts in the field patients receiving 0.5 mg ranibizumab plus PDT
were consulted and manufacturers’ submissions were compared with PDT plus sham injection. Pegaptanib
examined. patients lost statistically significantly fewer letters after
Review methods: The quality of included studies was 12 months of treatment than the sham group [mean
assessed using standard methods and the clinical letters lost: 7.5 (0.3 mg), 6.5 (1.0 mg) or 10 (3.0 mg) vs
effectiveness data were synthesised through a narrative 14.5 (sham)]. In the MARINA and ANCHOR trials,
review with full tabulation of results. A model was ranibizumab patients gained letters of visual acuity at
developed to estimate the cost-effectiveness of 12 months whereas patients with sham injection or
ranibizumab and of pegaptanib (separately), compared PDT lost about 10 letters (p < 0.001) and in the PIER
with current practice or best supportive care, from the study, ranibizumab patients lost significantly fewer than
perspective of the NHS and Personal Social Services. the sham injection group. Significantly fewer patients
Two time horizons were adopted for each model. The receiving pegaptanib or ranibizumab deteriorated to
first adopted time horizons determined by the available legal blindness compared with the control groups.
trial data. The second analysis extrapolated effects of Adverse events were common for both pegaptanib
treatment beyond the clinical trials, adopting a time and ranibizumab but most were mild to moderate.
horizon of 10 years. Drug costs for 1 year of treatment were estimated as
Results: The combined analysis of two randomised £4626 for pegaptanib and £9134 for ranibizumab. Non-
controlled trials (RCTs) of pegaptanib [0.3 mg (licensed drug costs accounted for an additional £2614 for
dose), 1.0 mg and 3.0 mg] versus sham injection in pegaptanib and £3120 for ranibizumab. Further costs
patients with all lesion types was reported by three are associated with the management of injection-
publications (the VISION study). Three published RCTs related adverse events, from £1200 to £2100. For
of ranibizumab were identified (MARINA, ANCHOR, pegaptanib compared with usual care, the incremental
FOCUS), and an additional unpublished RCT was cost-effectiveness ratio (ICER) ranged from £163,603
provided by the manufacturer (PIER). Significantly more for the 2-year model to £30,986 for the 10-year model.
patients lost less than 15 letters of visual acuity at 12 Similarly, the ICERs for ranibizumab for patients with
months when taking pegaptanib (0.3 mg: 70% of minimally classic and occult no classic lesions,
patients; 1.0 mg: 71% of patients; 3.0 mg: 65% of compared with usual care, ranged from £152,464 for
patients) or ranibizumab (0.3 mg: 94.3–94.5%; 0.5 mg: the 2-year model to £25,098 for the 10-year model.
94.6–96.4%) than sham injection patients (55% versus Conclusions: Patients with AMD of any lesion type
pegaptanib and 62.2% versus ranibizumab) or, in the benefit from treatment with pegaptanib or ranibizumab
case of ranibizumab, photodynamic therapy (PDT) on measures of visual acuity when compared with sham
(64.3%). The proportion of patients gaining 15 letters injection and/or PDT. Patients who continued iii
© Queen’s Printer and Controller of HMSO 2008. All rights reserved.
Abstract
treatment with either drug appeared to maintain investigate the role of verteporfin PDT in combination
benefits after 2 years of follow-up. When comparing with these drugs. Studies are also needed to assess
pegaptanib and ranibizumab, the evidence was less adverse events outside the proposed RCTs, to consider
clear due to the lack of direct comparison through the optimal dosing regimes of these drugs and the
head-to-head trials and the lack of opportunity for benefits of re-treatment after initial treatment, and to
indirect statistical comparison due to heterogeneity. review costing in more detail. Health state utilities and
The cost-effectiveness analysis showed that the two their relationship with visual acuity and contrast
drugs offered additional benefit over the comparators sensitivity, the relationship between duration of vision
of usual care and PDT but at increased cost. Future loss and the quality of life and functional impact of
research should encompass trials to compare vision loss, behavioural studies of those genetically at
pegaptanib with ranibizumab and bevacizumab, and to risk are other topics requiring further research.
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Health Technology Assessment 2008; Vol. 12: No. 16
Contents
Glossary and list of abbreviations ............. vii Appendix 3 Quality assessment ................ 121
Executive summary .................................... ix Appendix 4 Data extraction tables ............ 123
1 Background ................................................ 1 Appendix 5 List of selected excluded
Description of health problem ................... 1 studies ......................................................... 147
Current service provision ........................... 11
Description of technology under Appendix 6 List of eligible abstracts ......... 149
assessment .................................................. 13
Appendix 7 List of ongoing studies .......... 151
2 Definition of the decision problem ............ 17
Decision problem ....................................... 17 Appendix 8 Critique of industry
Overall aims and objectives of submissions ................................................. 153
assessment .................................................. 17
Appendix 9 Ocular adverse events in study
3 Assessment of clinical effectiveness .......... 19 eye: CIC information from ranibizumab
Methods for reviewing effectiveness .......... 19 studies ......................................................... 157
Results ........................................................ 20
Discussion of clinical effectiveness ............. 38 Appendix 10 Non-ocular adverse events:
Summary of clinical effectiveness .............. 39 CIC information from ranibizumab
studies ......................................................... 159
4 Assessment of cost-effectiveness .............. 43
Introduction ............................................... 43 Appendix 11 Summary of measures
Systematic review of existing reported in studies included in the review
cost-effectiveness evidence ......................... 43 of quality of life in AMD ............................ 161
Independent economic assessment ........... 58
Appendix 12 Critical appraisal checklist
5 Assessment of factors relevant to the of economic evaluation in Pfizer
NHS and other parties .............................. 87 submission .................................................. 165
6 Discussion ................................................... 89 Appendix 13 Critical appraisal checklist
Statement of principal findings ................. 89 of economic evaluation in Novartis
Strengths and limitations of the submission .................................................. 167
assessment .................................................. 93
Uncertainties .............................................. 94 Appendix 14 Variables included in
Other relevant factors ................................ 94 probabilistic sensitivity analysis .................. 169
7 Conclusions ................................................ 97 Appendix 15 Additional analysis
Implications for service provision .............. 97 commissioned by the NHS R&D HTA
Suggested research priorities ..................... 98 Programme on behalf of the National
Institute for Health and Clinical
Acknowledgements .................................... 99 Excellence ................................................... 171
References .................................................. 101 Health Technology Assessment reports
published to date ....................................... 203
Appendix 1 Protocol methods .................. 109
Health Technology Assessment
Appendix 2 Literature search strategies ..... 113 Programme ................................................ 219
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Health Technology Assessment 2008; Vol. 12: No. 16
Glossary and list of abbreviations
Technical terms and abbreviations are used throughout this report. The meaning is usually clear from
the context, but a glossary is provided for the non-specialist reader. In some cases, usage differs in the
literature, but the term has a constant meaning throughout this review.
Glossary
Vascular endothelial growth factor (VEGF, contributors to physiological or pathological
VEGF-A) This is a protein that plays a critical conditions that can stimulate the formation of
role in angiogenesis (development of new new blood vessels.
blood vessels) and serves as one of the
List of abbreviations
ACD Appraisal Consultation Document FA fluorescein angiography
AMD age-related macular degeneration FDA Food and Drug Administration
AREDS Age-related Eye Disease Study ICD International Classification of
Diseases
ARM age-related maculopathy
ICER incremental cost-effectiveness ratio
ARMD age-related macular degeneration
ITT intention-to-treat
BNF British National Formulary
IVI Impact of Vision Impairment
CI confidence interval
MAR minimum angle of resolution
CIC commercial-in-confidence
CNV choroidal neovascularisation MLRM multinomial logistic regression
model
CRD Centre for Reviews and
Dissemination NEI-VFQ National Eye Institute Visual
Function Questionnaire
CVI Certificate of Vision Impairment
NICE National Institute for Health and
DA optic disc area (measurement of Clinical Excellence
lesion size: DA = 2.54 mm2)
OCT optical coherence tomography
ETDRS Early Treatment Diabetic
Retinopathy Study PDT photodynamic therapy
continued
vii
© Queen’s Printer and Controller of HMSO 2008. All rights reserved.
Glossary and list of abbreviations
List of abbreviations continued
POMS Profile of Mood States SF-36 Short Form with 36 Items
PSS Personal Social Services SPC Summary of Product
Characteristics
QALY quality-adjusted life-year
TAP Treatment of Age-related Macular
QWB Quality of Well-Being Degeneration with Photodynamic
Therapy
RCT randomised controlled trial
TTO time trade-off
RNIB Royal National Institute for the
Blind VAR visual acuity rating
RPE retinal pigment epithelium VEGF, vascular endothelial growth factor
VEGF-A (-A).
SD standard deviation
VIP Verteporfin in Photodynamic
SG standard gamble Therapy
SF-12 Short Form with 12 Items
All abbreviations that have been used in this report are listed here unless the abbreviation is well known (e.g. NHS), or
it has been used only once, or it is a non-standard abbreviation used only in figures/tables/appendices in which case
the abbreviation is defined in the figure legend or at the end of the table.
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