Etanercept and Infliximab for the Treatment of Psoriatic Arthritis

331 Pages·2005·1.49 MB·English

CRD/CHE Technology Assessment Group

Etanercept and Infliximab for the Treatment of Psoriatic Arthritis
Technology Assessment Report
commissioned by the HTA Programme on behalf of
The National Institute for Clinical Excellence

Etanercept and Infliximab
for the Treatment of Psoriatic Arthritis

Produced by CRD/CHE Technology Assessment Group (Centre for Reviews
and Dissemination / Centre for Health Economics), University of
York
Authors Dr Nerys Woolacott, Research Fellow, Centre for Reviews and
Dissemination, University of York, York
Ms Yolanda Bravo Vergel, Research Fellow, Centre for Health
Economics, University of York, York
Dr Neil Hawkins, Research Fellow, Centre for Health Economics,
University of York, York
Ms Anita Kainth, Research Fellow, Centre for Reviews and
Dissemination, University of York, York
Ms Zarnie Khadjesari, Research Fellow, Centre for Reviews and
Dissemination, University of York, York
Ms Kate Misso, Information Officer, Centre for Reviews and
Dissemination, University of York, York
Ms Kate Light, Information Officer, Centre for Reviews and
Dissemination, University of York, York
Mr Christian Asseburg, Research Fellow, Centre for Health
Economics, University of York, York
Mr Stephen Palmer, Senior Research Fellow, Centre for Health
Economics, University of York, York
Dr Karl Claxton, Senior Lecturer, Centre for Health Economics,
University of York, York
Dr Robert Chalmers, Consultant Dermatologist, Dermatology
Centre, University of Manchester, Manchester
Dr Ian Bruce, Senior Lecturer and Consultant Rheumatologist,
ARC Epidemiology Unit, University of Manchester, Manchester
Professor Mark Sculpher, Professor of Health Economics, Centre
for Health Economics, University of York, York
Dr Rob Riemsma, Senior Research Fellow, Centre for Reviews
and Dissemination, University of York, York
Correspondence to Dr Nerys Woolacott, Research Fellow, Centre for Reviews and
Dissemination, University of York, York YO10 5DD.
Email: [email protected]
Tel. [phone] Fax [phone]
Date completed 4th February 2005
Expiry date February 2007
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Etanercept and Infliximab for the Treatment of Psoriatic Arthritis
Contributions of authors
Nerys Lead reviewer responsible for writing the protocol, all aspects of the
Woolacott clinical evaluation and co-ordinating the final report.
Yolanda Bravo Responsible for the systematic review of economic evaluations,
Vergel implementation of the economic model, re-analysis of the company
submissions. Contributed to the protocol and report writing.
Neil Hawkins Contributed to the evidence synthesis, development of the economic
model, contributed to the protocol and report writing.
Anita Kainth Reviewer involved in the clinical evaluation section, involved in
study selection, data extraction, validity assessment
Zarnie Reviewer involved in the clinical evaluation section, involved in
Khadjesari study selection, data extraction, validity assessment and writing the
final report.
Christian Developed and implemented the evidence synthesis
Asseburg
Stephen Contributed to the development of the economic model
Palmer
Karl Claxton Contributed to the development of the economic model
Kate Misso Devised the search strategy and carried out the literature searches;
Kate Light Wrote the search methodology sections of the report.
Ian Bruce Provided input at all stages, contributed to the protocol, commented
on various drafts of the report and contributed to the discussion
section of the report.
Mark Sculpher Provided input at all stages, commented on various drafts of the
report; overall responsibility for the economic evaluation sections of
the report.
Rob Riemsma Provided input at all stages, commented on various drafts of the
report; overall responsibility for project co-ordination.

CRD/CHE Technology Assessment Group
The Technology Assessment Review team at the University of York is drawn from
two specialist centres: the Centre for Reviews and Dissemination (CRD) and the
Centre for Health Economics (CHE).

CRD undertakes reviews of research about the effects of interventions used in health
and social care (www.york.ac.uk/inst/crd). The centre maintains various databases,
provides an enquiry service and disseminates results of research to NHS decision
makers.

CHE undertakes research and training in all areas of health economics
(www.york.ac.uk/inst/che). The bulk of the input into the TARs comes from the
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Etanercept and Infliximab for the Treatment of Psoriatic Arthritis
programme for economic evaluation and health technology assessment which
specialises in decision analysis and Bayesian methods in economic evaluations (see
http://www.york.ac.uk/inst/che/teehta.htm).

Recent TARs undertaken by CRD/CHE at York relate to topotecan, pegylated
liposomal doxorubicin hydrocholoride and paclitaxel for second-line or subsequent
treatment of advanced ovarian cancer; methylphenidate, dexamfetamine and
atomoxetine for the treatment of attention deficit hyperactivity disorder; and
clopidogrel and modified-release dipyridamole for the prevention of occlusive
vascular events.

Conflicts of interest
None of the authors have conflicts of interest.

Relationship of reviewer(s) with sponsor
Source of funding: This report was commissioned by the NHS R&D HTA
Programme.

Acknowledgements
We thank the expert advisory panel for their useful advice and constructive comments
on the report. We also wish to thank Professor Tony Ades of the MRC Health
Services Research Collobaration at the University of Bristol for his help and advice
on the mixed treatment comparison model applied in the evidence synthesis.

The views expressed in this report are those of the authors and not necessarily those
of the NHS R&D Programme.
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Etanercept and Infliximab for the Treatment of Psoriatic Arthritis
Table of Contents
Executive Summary 11
List of Abbreviations 20
Definitions of Terms 22
1 Aim of the review 30
2 Background 30
2.1 Description of underlying health problem 30
2.2 Assessment of treatment response in psoriatic arthritis 33
2.3 Current service provision 37
2.4 Description of new intervention 39
3 Methods 41
3.1 Search strategy 41
3.2 Inclusion and exclusion of studies 42
3.2.1 Study selection 42
3.2.2 Inclusion/ exclusion criteria 43
3.2.2.1 Efficacy of interventions 43
3.2.2.2 Adverse events of interventions 44
3.2.2.3 DMARDs for treatment of psoriatic arthritis 45
3.2.2.4 Economic evaluations – systematic review 45
3.2.3 Data extraction strategy 45
3.2.4 Quality assessment strategy 47
3.2.4.1 Efficacy of interventions 47
3.2.4.2 Adverse effects of interventions 47
3.2.4.3 DMARDs for treatment of psoriatic arthritis 47
3.2.4.4 Economic evaluations – systematic review 47
3.2.5 Data analysis 48
3.2.5.1 Efficacy of interventions 48
3.2.5.2 Adverse effects of interventions 48
3.2.5.3 DMARDs for treatment of psoriatic arthritis 49
3.2.5.4 Economic evaluations – systematic review 49
4 Clinical evaluation 50
4.1 Quantity of research available 50
4.2 Efficacy of interventions 50
4.2.1 Efficacy of etanercept 50
4.2.1.1 Efficacy after 12 weeks treatment 55
4.2.1.2 Efficacy after 24 weeks treatment 56
4.2.1.3 Long-term follow-up 57
4.2.1.4 Summary of the efficacy of etanercept in the treatment of
psoriatic arthritis 57
4.2.2 Efficacy of infliximab 58
4.2.2.1 Data from ongoing trials 61
4.2.2.2 Summary of the efficacy of infliximab in the treatment of
psoriatic arthritis 62
4.3 Adverse events 62
4.3.1 Adverse Effects of Etanercept 62
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4.3.1.1 Information from standard reference texts 62
4.3.1.2 Information from existing reviews of etanercept 63
4.3.1.3 Adverse events for etanercept: data from included studies 63
4.3.1.4 Summary of adverse events for etanercept 65
4.3.2 Adverse Effects of Infliximab 65
4.3.2.1 Information from standard reference texts 65
4.3.2.2 Information from existing reviews of infliximab 65
4.3.2.3 Adverse Events for Infliximab: data from included studies 66
4.3.2.4 Summary of adverse effects of infliximab 68
4.4 DMARDs for the treatment of psoriatic arthritis 69
4.4.1 Efficacy of DMARDs 69
4.4.2 Adverse effects of DMARDs 76
4.5 Evidence synthesis 78
4.5.1 Aim 78
4.5.2 Outcomes of interest 79
4.5.3 Evidence 80
80
Trial
4.5.4 Key assumptions for the evidence synthesis 81
4.5.5 Formal model description 82
4.5.6 Evidence synthesis results 84
5 Economic review 87
5.1 Published economic evaluations 87
5.2 Company submissions 87
5.2.1 Wyeth’s cost-effectiveness model 87
5.2.1.1 Summary 87
5.2.1.2 Limitations of the Wyeth model 89
5.2.2 Schering Plough’s cost-effectiveness model 92
5.2.2.1 Summary 92
5.2.2.2 Limitations of the Schering Plough model 94
6 Economic modelling 96
6.1 Introduction 96
6.2 Methods 96
6.2.1 Overview 96
6.2.2 Comparators 97
6.2.3 Model structure 98
6.2.4 Parameter estimates 101
6.2.5 Analysis 111
6.3 Results 111
6.3.1 Expected costs and QALYs 111
6.3.2 Probabilistic sensitivity analysis 115
6.3.3 Cost breakdown 117
6.3.4. Alternative assumptions 118
6.4 Interpretation and comparison with manufacturer models 120
7 Discussion 126
7.1 General points 126
7.2 Clinical evaluation 127
7.3 Economic evaluation 129
8 Conclusions 135
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9 References 136
10 Appendices 147
10.1 Literature searches 147
10.1.1 Clinical effectiveness evidence 147
10.1.1.1 Search A: Randomized controlled trials (RCTs) of etanercept or
infliximab in psoriatic arthritis 147
10.1.1.2 Search B: Randomized controlled trials (RCTs) of comparator
treatments in psoriatic arthritis 150
10.1.1.3 Search C: Randomized controlled trials (RCTs) and reports of
adverse events (AEs) for infliximab 158
10.1.1.4 Search D: Reports of adverse events of comparators treatments
167
10.1.2 Cost-effectiveness evidence 168
10.1.2.1 Search 1: Economic evaluations of etanercept or infliximab in
psoriatic arthritis 168
10.1.2.2 Search 2: Economic evaluations of comparator treatments in
psoriatic arthritis 172
10.1.2.3 Search 3: Quality of life (QoL) measures in psoriatic arthritis 177
10.1.2.4 Search 5: Treatment pathways for psoriatic arthritis 189
10.1.2.5 Search 6: Internet searches to locate guidelines for psoriatic
arthritis 192
10.1.3 Additional searches 193
10.1.3.1 Citation searching: 193
10.1.3.2 Search for cohort studies: 194
10.1.3.3 Search for publications about the Toronto Psoriatic Arthritis
Program: 194
10.2 Quality assessment tool 197
10.3 Excluded studies 198
10.4 Data extraction tables: intervention efficacy 200
10.4.1 Data extraction tables: intervention efficacy – etanercept 201
10.4.2 Data extraction tables: intervention efficacy – infliximab 212
10.5 Data extraction tables: intervention adverse events 216
10.5.1 Data extraction tables: intervention adverse events - etanercept 216
10.5.2 Data extraction tables: intervention adverse events - infliximab 237
10.6 Adverse events data summary 260
10.6.1 Adverse effects of etanercept 260
10.6.1.1 Information from standard reference texts 260
10.6.1.2 Information from existing reviews of etanercept 260
10.6.1.3 Adverse Events for Etanercept: data from included studies 262
10.6.1.4 Summary of adverse events data for etanercept 265
10.6.2 Adverse Effects of Infliximab 274
10.6.2.1 Information from standard reference texts 274
10.6.2.2 Information from existing reviews of infliximab 275
10.6.2.3 Adverse Events for Infliximab: data from included studies 277
10.6.2.4 Summary of adverse events data for infliximab 279
10.7 Data extraction tables: comparator efficacy 290
10.8 Evidence synthesis model WinBUGS code 314
10.9 Data extraction and quality assessment tables for economic evaluations
318
10.9.1 Cost-effectiveness model (Wyeth) – data extraction 318
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10.9.2 Cost-effectiveness model submitted by Wyeth – quality assessment
320
10.9.3 Cost-effectiveness model (Schering Plough) – data extraction 322
10.9.4 Cost-effectiveness model (Schering Plough) – quality assessment
323
10.10 Details of adjustment for placebo response in the York Model 325
10.11 Evidence on annual HAQ progression whilst on anti-TNF drugs 327
10.12 Details of costs used in the York Model 328
10.12.1 Unit costs 328
10.12.2 Drug acquisition costs10.12.3 Drug administration costs 329
10.12.3 Drug administration costs 330
10.12.4 Drug monitoring costs 331

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List of Tables
Table 4.2.1. Results of quality assessment for trials of etanercept 50
Table 4.2.2 Summary of trial population characteristics 52
Table 4.2.3 Etanercept efficacy outcomes – RCT data 54
Table 4.2.4 Pooled etanercept efficacy data – outcomes at 12 weeks 56
Table 4.2.5 Etanercept efficacy outcomes – uncontrolled follow-up data 57
Table 4.2.6. Results of quality assessment for trials of infliximab 58
Table 4.2.7 Summary of trial population characteristics 59
Table 4.2.8 Summary of outcome data for infliximab vs. placebo 60
Table 4.3.1 Adverse events reported most frequently during 24 weeks treatment with
etanercept 64
Table 4.3.2 Adverse events reported most frequently during 16 to 50 weeks
treatment with infliximab 67
Table 4.4.1 Characteristics of RCTs of comparator drugs for the treatment of psoriatic
arthritis 70
Table 4.4.2 Summary of continuous data from placebo controlled trials 72
Table 4.4.3 Summary of dichotomous data from placebo controlled trials 73
Table 4.4.4 Summary of continuous data from methotrexate controlled trials 73
Table 4.5.1. Response rates (in terms of PsARC) reported in the trials and used in the
evidence synthesis 80
Table 4.5.2 Data on HAQ change conditional on treatment response (in terms of
PsARC) 80
Table 4.5.3 Indirect information on the change in HAQ that applies to treatment
responders and treatment non-responders 81
Table 4.5.4 Change in HAQ score without treatment 81
Table 4.5.5 Results of the evidence synthesis 85
Table 5.2.1 Base-case results from the Wyeth model 89
Table 5.2.2 Base-case results for the Active Joint version of the Schering Plough
model with a 5 year time horizon 94
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Table 5.2.3 Base-case results for the Chronic Active Joint version of the Schering
Plough model with a 30 year time horizon 94
Table 6.2.1 Anti-TNF therapeutic indications for psoriatic arthritis 98
Table 6.2.2. List of parameter estimates used in the York Model 103
Table 6.2.3 Summary of costs used for infliximab and etanercept (2004 UK £). Full
details are provided in Appendix 10.12. 109
Table 6.2.4. Direct used in the OLS regression based on Kobelt (2002)29 uprated to
2004 prices (UK, £) 110
Table 6.3.1 Base-case cost-effectiveness results under the rebound scenario of
rebound equal to gain 113
Table 6.3.2 Base-case cost-effectiveness results under the rebound scenario of
rebound equal to natural history 114
Table 6.3.3 Results of a scenario analysis to assess the sensitivity of model results to
alternative assumptions. All scenarios relate to males, a 10-year time horizon and the
assumption of rebound equal to gain 119
Table 6.3.4 Results of a scenario analysis to assess the sensitivity of model results to
alternative assumptions. All scenarios relate to males, a 10-year time horizon and the
assumption of rebound equal to natural history 119
Table 6.4.1. Comparison of the modelling approach and main assumptions used in the
Schering Plough, Wyeth and York models. 123
Table 10.6.1: Pooled adverse events data - Etanercept 24 weeks (6 months) follow-up
266
Table 10.6.2: Pooled adverse events data – Etanercept 1 year follow-up 269
Table 10.6.3: Pooled adverse events data – Etanercept 2 years or more follow-up 271
Table 10.6.4 Studies that met the inclusion criteria for evaluation of the adverse
effects of infliximab 281
Table 10.6.5: Adverse events of infliximab in psoriatic arthritis 282
Table 10.6.6: Adverse events with infliximab in patients with Rheumatoid arthritis 284
Table 10.6.7: Adverse events of infliximab in psoriasis with no DMARDs 286
Table 10.6.8: Summary of adverse events from studies in patients with Crohn’s
disease 288

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List of Figures
Figure 5.2.1. Illustration of the base-case rebound scenario for etanercept in the
Wyeth model: rebound equal to gain 91
Figure 5.2.2 Illustration of a third rebound scenario for etanercept not considered in
the Wyeth model: rebound to natural history progression 92
Figure 6.2.1 A simplified version of the structure of the York Model 99
Figure 6.3.1 Cost-effectiveness acceptability curves: males, 10-year time horizon,
rebound equal to gain. Dotted vertical line shows the position of the incremental cost-
effectiveness ratio of etanercept relative to palliative care. 116
Figure 6.3.2. Cost-effectiveness acceptability curves: males, 40-year time horizon,
rebound equal to gain. Dotted vertical line shows the position of the incremental cost-
effectiveness ratio of etanercept relative to palliative care. 116
Figure 6.3.3. Cost-effectiveness acceptability curves: males, 10-year time horizon,
rebound equal to natural history. Dotted vertical line shows the position of the
incremental cost-effectiveness ratio of etanercept relative to palliative care. 117
Figure 6.3.4. Cost-effectiveness acceptability curves: males, 40-year time horizon,
rebound equal to natural history. Dotted vertical line shows the position of the
incremental cost-effectiveness ratio of etanercept relative to palliative care. 117
Figure 6.3.5 The proportion of drug costs to other costs for etanercept and infliximab
for different time horizons (males, rebound equal to gain). 118

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