Improving Patient Care with Biologics in the Management of Rheumatoid Arthritis - (Sponsored by Celltrion Healthcare) - NHS England
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Improving Patient Care with Biologics
in the Management of Rheumatoid Arthritis
(Sponsored by Celltrion Healthcare)
1
Session Aims
Our aims of this session are to discuss:
✓ How can we improve rheumatoid arthritis (RA) patient access to biologics?
✓ How can we move forward in the area of RA management?
✓ How can we manage RA appropriately without burdening healthcare budget?
3
Agenda
The Roles of Biosimilars in Patient HoUng Kim
Session 1. (Head of Strategy and Operation Division, Celltrion
Access to Biologics in UK Healthcare)
Dr. Ben Parker
(Consultant Rheumatologist, Kellgren Centre for
Rheumatoid Arthritis: Biologics,
Session 2. Rheumatology, Manchester Royal Infirmary, NIHR
Clinical Need and NICE Manchester Biomedical Research Centre, Manchester
University Hospitals NHS Foundation Trust)
Improving Patient Care with
Session 3. Biologics in the Management of RA: Alistair Curry
(Partner, Sirius Market Access)
Economic Perspective
4
The Roles of Biosimilars in Patient
Access to Biologics in UK
5
What are biologics and why is accessibility important?
▪ Definition of biologics:
Biologics are medicines that are made or derived from a biological source and as such are complex, with inherent variability
in their structure.1
1. https://www.england.nhs.uk/wp-content/uploads/2015/09/biosimilar-guide.pdf 6
2. https://www.celltrion.com/en/biosimilar/medicine.do
What are biologics and why is accessibility important?
▪ NHS England (Commissioning Framework for Biological Medicines)1
“Biological medicines are important, clinically effective medicines which can significantly impact on a patient’s
disease”
▪ American College of Rheumatology Position Statement2
“Biologics are expensive but vitally important therapeutic options for patients with rheumatic diseases. Given their
effectiveness and potential to reduce long-term disability, patients should have affordable access to biologic
therapy without undue delay”
▪ The European League Against Rheumatism (Position Paper on Access to Health Care for People with Rheumatic
and Musculoskeletal Disease (RMDs))3
“Access to quality health care is one of the main concerns for people with RMDs and other chronic conditions in
European countries”
1. NHS England. Commissioning framework for biological medicines (including biosimilar medicines), 12 September 2017
2. American College Rheumatology position statement. Patient Access to Biologics 05/2018
3. EULAR. EULAR position paper on access to healthcare for people with rheumatic and musculoskeletal diseases (RMDs). 2015
7
EULAR position paper (2015) : What are main access barriers for people with
rheumatic and musculoskeletal disease?
2. Performance and organizations of
1. Health systems coverage and management
health care services
• Insufficient supply and coverage • Delay in timely access to diagnosis and treatment
• Narrow approach of healthcare – Silos between health systems • Lack of care pathways & standards of care
and social welfare system • Lack of integration of electronic information
3. Interaction between patients and health professionals,
4. Availability and affordability of medicines and treatments
health systems and treatments
• Unequal eligibility rules for treatments and medicines
• Insufficient time between patients and health professionals
• Delay in the marketing authorization, pricing and reimbursement
• Cultural differences and power imbalance between patients and
system
health professionals
• Insufficient patient involvement in the development of new
• Insufficient access to other health professionals (nurses, etc.)
therapies
1. EULAR. EULAR position paper on access to healthcare for people with rheumatic and musculoskeletal diseases (RMDs). 2015 8
EULAR position paper (2015) : What are main access barriers for people with
rheumatic and musculoskeletal disease?
Availability and affordability of medicines and treatments
Unequal eligibility rules for treatments and medicines How to overcome
the barrier for UK
patients?
Delay in the marketing authorization, pricing and reimbursement system
Insufficient patient involvement in the development of new therapies
1. EULAR. EULAR position paper on access to healthcare for people with rheumatic and musculoskeletal diseases (RMDs). 2015 9
Disparities in access to biologics in Europe
▪ Biologics are not always accessible to all patients with RA due to their high direct costs against a background of
restricted health care budget
Low access (0-1) Moderate access (2-3) High access (4-5)
Austria
Albania
Bulgaria Latvia Cyprus
Belarus
Croatia Lithuania Germany
Belgium
Estonia Macedonia Iceland
Czech
Malta Netherlands Ireland
Denmark
Montenegro Romania Luxembourg
Finland
Poland Russia Norway
France
Serbia Slovenia Portugal
Greece
Turkey Sweden Slovakia
Hungary
UK Ukraine Spain
Italy
Switzerland
* disease duration [any requirement (0 points), no requirement (1 point)], number of csDMARDs failed [more than two (0 points), two (1 point),
and fewer than two (2 points)], and level of disease activity [DAS28 cut-off > 3.2 or its equivalent (0 points), DAS28 cut-off ≤ 3.2 or its equivalent
(1 point), and no requirement (2 points)] criteria
1. Kaló Z, et al. Patient access to reimbursed biological disease-modifying antirheumatic drugs in the European region. Journal of Market Access & Health Policy. 2017;5(1):1345580. doi:10.1080/20016689.2017.1345580. 10
Unequal eligibility rules for treatments and medicines
▪ Clinical criteria regulating prescription of bDMARDs in RA differ significantly across Europe.
▪ UK, among the selected countries, has the most stringent DAS28 requirements; Nordic countries having the most
lenient criteria.
Norway
Sweden & Denmark
UK
* Composite score for restrictiveness of clinical criteria (0-5, score is composed of (1) minimum required disease duration, (2)
number of sDMARDs that have to be failed and (3) the level of DAS28) and GDP per capita (int/$), n=36. Size of the bubble is
proportional to the population size of each country. Dashed trend line is added to show the linear trend if without data from
Luxemburg, which can be considered ad outlier GDP, gross domestic product.
1. Putrik P et al., Variations in criteria regulating treatment with reimbursed biologic DMARDs across European countries. Are differences related to country’s wealth? Annals of Rheumatic Disease, 2013; doi:10. 1136 11How many patients are eligible for biologics in UK?
▪ Among the surveyed RA patients, only of 22% had access to biologics.1
▪ Patients with moderate disease activity have limited access to biologics until the disease progresses to DAS28 >5.1. 2
RA patient access to biologics in UK UK: RA patients
by disease severity3
Severe Moderate Mild
Total RA :
No. of patients with RA 88,000 166,000 146,000
400,000 Severe
22%
Mild
No. of RA patients treated with 36%
biologics
84,200 21%
No. of RA patients treated with anti- Moderate
TNFα
58,280 14% 42%
0 100000 200000 300000 400000 500000
1. Global Data Forecast and Market Analysis – Rheumatoid Arthritis, published Jan 2017
2. https://www.nras.org.uk/index.php/what-is-ra-article 12
3. Decision Resources Group. Detailed, Expanded Analysis (EU5) in Rheumatoid Arthritis, Current Treatment (2018)What is the current guideline in UK and what are the perspectives?
▪ NICE guideline set the criteria for starting bDMARDs: DAS28 >5.1 & failure of ≥ 2 csDMARDs1
▪ NRAS & BSR position paper on NICE guideline: “eligibility criteria (DAS28 of more than 5.1) are set too high”.2
▪ NICE TA375:
“The Committee concluded that all the technologies were
clinically effective for all subgroups, but could only consider
them as a cost-effective use of NHS resources for people
with severe active rheumatoid arthritis previously treated with
methotrexate.”
▪ NRAS “Biologics The Story So Far (2013)”
“ The BSR and others, including NRAS, will continue to
make the case to NICE for reducing the required DAS 28
score from 5.1.”
bDMARDs: biologic Disease-Modifying Anti-Rheumatic Drugs
csDMARDs: conventional synthetic DMARDs
1. NICE. TA375. C Deighton et al, Rheumatology 2010;49:1197–1199. Jan 2016 13
2. NRAS. Biologics The Story So Far. Sep 2013. Available at: https://www.nras.org.uk/data/files/Publications/Biologics-.pdfClinical Effectiveness : Earlier Introduction of Biologics
▪ There is an extremely rapid response (38% at 2 weeks)
▪ The majority of RA patients achieved remission (DAS remission: 68-71% at week 52 in RCTs and 90% at week 14 in
an open study)
▪ Long-term benefit is ensued (DAS benefits sustained at 8 years)
Rapid
Achieving
response ▪ NICE TA375 4.92:
remission “The Committee understood that there was clinical interest
in the use of biological DMARDs in people with moderate
active disease (that is, with a DAS28 of less than 5.1)
Long-term
benefit whose disease was not controlled on conventional
DMARDs.”
Clinical Benefits1
RCT: Randomized controlled trial
1. Emery, P. (2014). Why is there persistent disease despite biologic therapy? Importance of early intervention. Arthritis Research & Therapy, 16(3), 115. http://doi.org/10.1186/ar4594 14
2. NICE. TA375. C Deighton et al, Rheumatology 2010;49:1197–1199. Jan 2016Biosimilars: Game changer in decreasing economic burden of RA
▪ Significant savings can be made by introducing of biosimilars into the RA setting.
Potential savings Predicted budget impact of introduction of CT-P13 for the treatment of rheumatoid arthritis
(Mil euros) in the UK, Italy, France, and Germany
160 148.5
140
120 106.1
100
73.6 75.7
80 64.6
56.6
60
43.6 38.6
40 33.5
22.3 26.7 25.8
15.5 18.6
20 12.9
0
Scenario 1 Scenario 2 Scenario 3
(10% D.C, 20% market uptake) (20% D.C, 30% market uptake) (30% D.C, 40% market uptake)
2015 2016 2017 2018 2019
15
1. Gulácsi L. et al. (2015) Biosimilars for the management of rheumatoid arthritis: economic considerations, Expert Review of Clinical Immunology, 11:sup1, 43-52, DOI: 10.1586/1744666X.2015.1090313Biosimilars: Game changer in decreasing economic burden of RA
▪ Significant savings can be made by introducing of biosimilars into the RA setting.
NHS savings by switching from expensive medicines to better value and equally effective alternatives (2017/2018)
Medicine Treats Savings delivered
▪ “By delivering £324 million in
Rheumatoid diseases and
infliximab biosimilars uptake £99,400,000 savings in a single year from
inflammatory bowel diseases
switching to better value but
equally effective and safe
etanercept biosimilars uptake Rheumatoid diseases £60,300,000 medicines, the NHS has been able
to help more patients manage their
conditions.”
Certain cancers and
rituximab biosimilars uptake £50,430,000
rheumatoid conditions -Dr Jeremy Marlow, Executive Director of
Operational Productivity, NHS Improvement
… … …
Total savings for 10 medicines £324 million
16
1. NHS Improvement. The NHS saves ₤324 million in a year by switching to better value medicines. https://improvement.nhs.uk/news-alerts/nhs-saves-324-million-year-switching-better-value-medicines/What are the benefits of biosimilars?
▪ After the introduction of biosimilars, patients access dramatically increased while the treatment cost decreased.
▪ The savings enable more patients to access biologic therapy
Norway
17
1. Ferrario A. et al. Strategic procurement and international collaboration to improve access to medicines. Bulletin of the World Health Organization 2017;95:720-722. doi: http://dx.doi.org/10.2471/BLT.16.187344What are the benefits of biosimilars?
▪ After the introduction of biosimilars, patients access dramatically increased while the treatment cost decreased.
▪ The savings enable more patients to access biologic therapy
Denmark (Danish hospitals in total) Stockholm, Sweden Costs Patients
Costs Patients
(DDK) (DDD)
DDD: defined daily dose
1. Christensen HR. Considerations and reflections concerning implementation of biosimilar MABs in the clinic – focus on trastuzumab. http://events.eahp.eu/pdfs/23ac/062.pdf 18
2. Stockholm County Council’s data on file (Approved for use)UK: Uptake of biosimilar is increasing
▪ NHS commissioning framework for biological medicines : “The NHS has already benefited from significant savings on
some medicines and it is getting better at adopting biosimilars.”1
1. NHSi. Commissioning framework for biological medicines (including biosimilar medicines. https://www.england.nhs.uk/wp-content/uploads/2017/09/biosimilar-medicines-commissioning-framework.pdf
2. Infliximab is used to treat rheumatology conditions and inflammatory bowel disease; etanercept is used for rheumatology conditions. These biosimilars came onto the market in March 2015 and April 2016 respectively.(Source: Rx-Info Define)19
3. Keith R. Optimizing medicines use, value and funding Dec 2017.Still, RA patient access to biologics is low in UK
▪ Volume of biologics in UK increased by 12% while 45-48% in Nordic countries1
▪ “Many patients and rheumatology professionals find the current guidelines frustratingly restrictive.” 2
60 Volume increase after introduction of biosimilar
50 48
45
Volume (2016/before
biosimilar, %)
40
30
19
20
12
10
0
UK Norway Denmark Total EU
1. The Impact of Biosimilar Competition in Europe, QuintilesIMS, May 2017
2. NRAS. Biologics The Story So Far. Sep 2013. Available at: https://www.nras.org.uk/data/files/Publications/Biologics-.pdf 20Collaborative work is essential to improve treatment outcome
21Conclusion: How to benefit from biosimilars in RA management
Creating sustainable healthcare environment
• High cost of biologic therapy
Needs
Collaborative
• Better-cost alternatives to reference medicinal products work
Maximize
• Possible to put drugs out to tender to reduce the price of the benefit
Roles original biologics HCP &
of biosimilar
system &
manufacturers
• Reduce the pressure on healthcare budgets
• Increase patients’ access to biologics
Effects • Increase patients’ access to new regimens and new drugs
22Celltrion Healthcare, Global Biosimilar Leader
• Leading global marketing & distribution company specializing in the biosimilar market
37 123 3
Global Partners Countries and Regions Approved and
for Distribution Marketed
Products
World′s 1st World′s 1st
mAb Biosimilar 3rd Biosimilar
mAb Biosimilar
in Hemato-oncology Approved by EMA
Approved by EMA
Approved by EMA (Oncology)
(Immunology)
(Hematology) Feb 2018
Sep 2013
Feb 2017
mAb, monoclonal antibody
2Celltrion Healthcare Mission:
As the leading biosimilar company,
• Improve biosimilar manufacturing process
• Communicate with HCPs about biosimilar
• Educate patients about biosimilar
• Collaborate with policymakers
• Support sustainable healthcare environment
More patients can receive better treatment without
increasing healthcare cost if stakeholders
collaboratively creates a conducive system for better
accessibility to biologics treatments.
23Thank you
4th Fl., 19, Academy-ro 51beon-gil, Yeonsu-gu, Incheon, South Korea, 406-840
Tel: +82-32-850-6400 / Fax: +82-32-850-6498 / Email: gmkt@celltrion.com
www.celltrionhealthcare.com
24Rheumatoid Arthritis: Biologics,
Clinical Need and NICE
Dr Ben Parker PhD, FRCP
Consultant Rheumatologist, Kellgren Centre for
Rheumatology, Manchester Royal Infirmary
Honorary Senior Lecturer, University of
Manchester
1Disclosures
• Clinical Expert NICE TA 375 and 415
• Committee Member NICE NG100 (RA update)
• Co-author of biologics guidelines for RA and AxSpA in Greater Manchester
• Received honoraria from: Celltrion, BMS, Abbvie, Novartis, Pfizer, GSK, AZ
2Outline
• What is Rheumatoid Arthritis (RA) and how is managed in UK?
• RA and NICE
• TA 375 (biologic therapies in RA)
• CG100 (management of RA)
• Unmet need in RA therapies in UK
3Rheumatoid Arthritis (RA)
• Chronic inflammatory arthritis
• Women higher prevalence than men
• Peak incidence 55 years
• Chronic inflammation of synovial joints
• Symptoms include joint pain, swelling and
stiffness
• Extra-articular manifestations common
4Impact of RA
Patient Broader Society
• Symptoms of active RA • High cost of therapies
– Pain, swelling, stiffness • Higher prevalence of co-morbidity,
– Fatigue including cancer and heart disease
• Need for analgesia and disease • High rate of unemployment
modifying therapy
• High rate of disability
• Difficulty with activities of daily
living, work and caring • Need for social care
5
Allaire et al. Arthritis and Rheum. 2009; 61(3):321-28Assessment tools in RA: Disease Activity
• DAS28 - 28 joints counted (excludes feet):
• Tender Joint Count
• Swollen Joint Count
• Visual Analogue Score of overall health
• Inflammation marker – ESR or CRP
• Overall score:
• ≥5.1 = severe
• 3.2-5.1 = moderate
• 2.6-3.2 = low disease activity
• ≤ 2.6 = remission
6Assessment tools in RA: Function
• Health Assessment Questionnaire Aspects of HAQ
(HAQ) • dressing and grooming
• Patient reported measure of • arising
disability
• eating
• Routinely collected in drug trials
and observational studies • walking
• Can ‘map’ onto EQ5D for cost • hygiene
effectiveness studies • reach
• grip
• common daily activities
7Treatment Aims in RA
• Diagnose early and initiate disease modifying therapies (DMARDs)
urgently
• therapies more effective in early disease
• Aim to reduce and eliminate any inflammatory joint disease
• Treat to target of remission/low disease activity
• Step-up and combination of therapies
• Monitor and manage flares, co-morbidity and function/disability
8Biologic therapies in RA
• Transformed care of RA with improved outcomes and reduced disease
progression
• Less surgery, joint replacement, co-morbidity, steroids
• Restricted to those with severe disease
• Safe and well tolerated but expensive:
• Oral methotrexate approx. £50-100/year
• Originator biologic approx. £8-9000/year
• Biosimilar biologic approx. £4-6000/year
• Biologics are biggest drug spend in NHS
9
Kings Fund 2018; NHS England Commissioning Framework 2017.NICE and RA
• NG100 – clinical guideline on management of rheumatoid arthritis –
July 2018
• Update of CG79 (2009)
• Several technology appraisals, e.g.
• TA375 – bDMARDs after failure of conventional DMARDs
• TA466 – baricitinib for active RA
• TA480 – tofacitinib for active RA
NB. Clinical guideline doesn’t cover aspects of care if technology appraisal available
10NICE TA375
• Multiple technology appraisal combining several previous single appraisals
• Prolonged appraisal: scope 2012, published 2016
• Patient groups, British Society of Rheumatology and Pharma all
represented
• Scope included broadening access to biological DMARDs (bDMARDs) to
patients with moderate disease (DAS28 3.2-5.1)
11NICE TA 375 - recommendations
• Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and
abatacept, all in combination with methotrexate, are recommended as options for
treating rheumatoid arthritis, only if:
• disease is severe, that is, a disease activity score (DAS28) greater than 5.1 and
• disease has not responded to intensive therapy with a combination of conventional
disease-modifying antirheumatic drugs (DMARDs) and
• Continue treatment only if there is a moderate response measured using EULAR
criteria at 6 months after starting therapy.
• After initial response within 6 months, withdraw treatment if a moderate EULAR
response is not maintained.
• Start treatment with the least expensive drug (taking into account administration
costs, dose needed and product price per dose).
12Impact on clinical practice
• Access to biologics for active RA unchanged since initial NICE TA in 2002
• Only in severe disease - DAS28 greater than 5.1
• Moderate patients excluded – unusual in Europe
• Clinical trials demonstrate efficacy of biologic therapies in patients with
DAS28 >3.2
• All licensed in patients with moderate-severe disease
• Moderate patients remain difficult to manage
• NG 100 treatment target is LDAS or remission
13Why are moderate patients excluded?
• NICE committee did not accept biological therapies were as cost effective
in moderate RA as in severe RA
• Cost implication significant
• Estimated 10-15% RA patients have severe disease
• Moderate patients may be up to 50-60%
• UK adult prevalence of RA estimated at 400,000
• Significant emphasis on disability (HAQ) progression on/off biological
therapies
14Are biologics cost effective in moderate RA?
• NICE committee discussed ICERs used in TA 375
• Severe RA: £41,600-25,300 in those with worst HAQ progression
• Moderate RA: £51,100-28,500 in those with worst HAQ progression
• No clear mechanism to identify patients with worst HAQ progression
15Progression of disability in RA
• Latent class analysis of data from two historical UK RA cohorts demonstrating 4 patterns of HAQ
progression in RA.
• This updated analysis was used in NICE TA 375, affecting ICER estimation significantly.
16
Norton S et al. Ann Rheum Dis. 2012: 71; 508Impact of HAQ progression on clinical practice
• Latent class analysis suggests not all patients HAQ scores progress
equally
- Benefit of biological therapies in moderate/severe?
- ICER varies depending on rate of HAQ progression
• NICE TA 375
- Need to have failed combination therapy to access biologic therapies
• NICE NG100
- Measure prognostic markers at diagnosis
- May impact on overall management
17Prognostic markers in RA
• Widely accepted markers of worse outcomes
- Seropositive, early erosions, persistently elevated inflammatory markers, poor
response to therapy
- Observational data - not tested in clinical trials
• Identification of poor prognostic factors
- Predict worse outcomes?
- Expensive therapies may be more cost effective in this group, in both moderate and
severe RA?
• Research recommendation in NG 100
18What does this mean in clinical practice?
• Access to effective therapies remains restricted in UK
• Moderate patients still at risk of significant progression of disability
- Higher risk of damage, disability, co-morbidity, surgery and steroid exposure
• Cost pressures significant
- Biosimilar therapies less expensive than originator
- Different acquisition costs used by NICE?
19How to move forwards?
• Review cost effectiveness using actual acquisition costs of medicines not
list price
• Test hypothesis that sub-groups of patients with RA have worse outcomes
and respond better to biologic therapies
• Stratified medicine studies of prognostic factors
• Weighted clinical trials with enriched populations
• Local and regional variation in implementation of NICE guidance
20Improving patient care with biologics
in the management of RA:
economic perspective
Alistair Curry
Partner, SIRIUS Market Access
London, UK
1Agenda
• Financial burden of RA
➢Direct costs and indirect costs
• Importance of effective RA management
➢Disease control is associated with higher HRQoL
and lower costs
• NICE and anti-TNF therapy: an economic perspective
➢Evaluating cost-effectiveness
➢Scope for earlier treatment of patients with moderate disease activity?
Abbreviations: HRQoL, health-related quality of life; RA, rheumatoid arthritis; TNF, tumour necrosis factor.
2Financial burden of RA
• Over 400,000 people living with RA in the UK1.
• Around 75% of new RA diagnoses in people of working age2.
• DWP estimate of £122 million incapacity benefit spent on RA between 2007-
083.
• Estimates of total cost of RA to UK economy, including NHS costs as well as
carer costs, costs of nursing homes, private expenditure, sick leave and work-
related disability are as high as £3.8 to £4.8 billion a year4.
1 The National Collaborating Centre for Chronic Conditions, 2018. Rheumatoid Arthritis. 2 National Audit Office, 2009. Services for people with rheumatoid arthritis.
3 Hansard. 11 May 2009: Column 570W. Incapacity Benefit: Arthritis. 4NICE, 2009. Rheumatoid arthritis: The management of rheumatoid arthritis in adults. Abbreviations: RA, rheumatoid arthritis. 3Financial burden of RA - Direct costs
• Estimated annual healthcare costs of RA to NHS England1
Activity\ Cost (£m)2
GP visits – unidentified cases prior to specialist 6
referral
Tests by GPs prior to specialist referral3 2
Total cost to NHS:
GP visits – diagnosed cases 146
£557 million per year
Monitoring tests by GPs following diagnosis 17
Drug costs in primary care 102
NHS rheumatology units 260
Surgery 24
1Adapted from National Audit Office, 2009. Services for people with rheumatoid arthritis. 2 Based on National Audit Office estimates of incidence and prevalence. 3 Excludes anti-cyclic citrullinated peptide (CCP) antibody tests.
Abbreviations: GP, general practitioner; RA, rheumatoid arthritis.
4Financial burden of RA - Indirect costs
• Percentage of people leaving work following RA
diagnosis1
30
reporting leaving work
Percentage of people
25
20 Estimated cost of sick leave and lost
15 employment due to RA:
10 £1.8 billion per year.
5
0
1 1-3 4-6 6-10 10+
Number of years since RA diagnosis
1Adapted from: The Economic Burden of Rheumatoid Arthritis, National Rheumatoid Arthritis Society, March 2010.
Abbreviations: RA, rheumatoid arthritis.
5Importance of effective RA management
• ERAS and ERAN studies1: risk of costly surgeries increases in patients with DAS28 > 3.2
RDAS LDAS LMDAS HMDAS HDAS
Intermediate surgery 1.00 1.13 (0.60-2.11) 1.33 (0.77-2.29) 1.80 (1.05-3.11)* 2.59 (1.49-4.52)*
Major surgery 1.00 1.65 (0.97-2.80) 2.07 (1.28-3.33)** 2.16 (1.32-3.52)** 2.48 (1.50-4.11)**
Results are hazard ratios (95% CI); * p < 0.001; ** p < 0.05
DAS28 categories Surgery categories
• RDAS (Remission): ≤ 2.6 • Intermediate: wrist, hand, and hind/ forefoot reconstructive
• LDAS (Low): 2.6 - 3.19 procedures.
• LMDAS (Low-moderate): 3.2 - 4.19 • Major: large joint arthroplasty (hips, knees, shoulders and
• HMDAS (High-moderate): 4.2 - 5.1 elbows), and surgery to the cervical spine.
• HDAS (High): > 5.1
1Nikiphorou et al. Ann Rheum Dis 2016; 75:2080–2086.
Abbreviations: CI, confidence interval; DAS, disease activity score; ERAN, Early Rheumatoid Arthritis Network; ERAS, Early Rheumatoid Arthritis Study; RA, rheumatoid arthritis.
6Importance of effective RA management
0.12
Annualised HAQ progression rates
0.1
• ERAS and ERAN studies1: HAQ progression
0.08
between years 1 and 5 is increased in patients
0.06
with DAS28 > 3.2 (data shown as ± 95% CI)
0.04
0.02 • A higher HAQ score indicates greater
0
functional impairment.
-0.02
-0.04
RDAS LDAS LMDAS HMDAS HDAS
1Nikiphorou et al. Ann Rheum Dis 2016; 75:2080–2086.
Abbreviations: CI, confidence interval; DAS, disease activity score; ERAN, Early Rheumatoid Arthritis Network; ERAS, Early Rheumatoid Arthritis Study; HAQ, Health Assessment Questionnaire; RA, rheumatoid arthritis.
7Importance of effective RA management
• Greater functional impairment is associated with higher disease-related hospital costs1
(disease-related hospital costs based on data from NOAR database).
Annual hospitalisation costs
HAQ
1Stevenson MD, et al. Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for the treatment of rheumatoid arthritis not previously treated with DMARDs and after the failure of
conventional DMARDs only: systematic review and economic evaluation. Health Technol Assess. Abbreviations: HAQ, Health Assessment Questionnaire; NOAR, Norfolk Arthritis Register; RA, rheumatoid arthritis.
8Importance of effective RA management
• Greater functional impairment and pain are associated with worse HRQoL1.
• In cost-effectiveness models, HAQ and pain should be considered simultaneously.
1Hernandez Alava et al. Rheumatology 2013; 52:944-950.
Abbreviations: HAQ, Health Assessment Questionnaire; HRQoL, health-related quality of life; RA, rheumatoid arthritis.
9How NICE has assessed cost-effectiveness
of biologic therapies for RA
• Over the years, NICE has recommended biologic treatments for patients with DAS28 > 5.1 in patients
failing conventional DMARD therapies.
• Cost-effectiveness estimates are based on modelling of how disease would progress without therapy
(HAQ) and likely impact of biologic therapy on reducing disease progression.
• Costs and HRQoL were modelled based on functional impairment (HAQ) and pain scores, and their
relationships with direct health care costs to the NHS as well as HRQoL (EQ-5D).
• NICE assesses treatments based on their estimated incremental cost per QALY gained,
with ICERs of < £20,000 to £30,000 considered cost-effective.
Abbreviations: DAS, disease activity score; DMARD, disease-modifying antirheumatic drug; EQ-5D, EuroQol Five Dimensions Questionnaire; HAQ, Health Assessment Questionnaire; HRQoL, health-related quality of life;
ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year; RA, rheumatoid arthritis.
10How NICE has assessed cost-effectiveness
of biologic therapies for RA
• In 2016, NICE reviewed its guidance for anti-TNF therapies alongside other biologics1.
• Appraisal committee noted that median ICER for biologics ranged from:
• £25,300 to £41,600 per QALY gained for DAS28 > 5.1 patients
• £28,500 to £51,100 per QALY gained for DAS28 > 3.2 patients
• NICE considered that biologic therapies in RA should only be recommended for
patients with DAS28 > 5.1 not responding to prior intensive combination DMARD
therapy.
1NICE, 2016. TA375: Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for RA not previously treated with DMARDs or after conventional DMARDs only have failed.
Abbreviations: DAS, disease activity score; DMARD, disease-modifying antirheumatic drug; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year; RA, rheumatoid arthritis; TNF, tumour necrosis factor.
11Why NICE should consider biologic
therapies in patients with DAS28 > 3.2
• There is high unmet need. No recommended treatment options for patients with DAS28 >
3.2 following prior combination DMARD therapy.
• Recommendations for DAS28 > 3.2 patients were appealed (unsuccessfully) by British
Society for Rheumatology and National Rheumatoid Arthritis Society1:
- They considered that lower end of ICER range was less than £30,000 per QALY and
therefore biologics should have been recommended by NICE.
• NICE will consult with stakeholders on whether guidance should be reviewed in 2019.
Biologics for patients with DAS28 > 3.2 likely to be further debated as part of review
decision.
1NICE, 2016. TA375: Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for RA not previously treated with DMARDs or after conventional DMARDs only have failed.
Abbreviations: DAS, disease activity score; DMARD, disease-modifying antirheumatic drug; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year; RA, rheumatoid arthritis.
12Summary
• The direct costs of RA to the NHS are significant but are lower than the costs to society
through lost work productivity.
• Patients with moderate disease activity (DAS28 > 3.2 to 5.1) have increased costs and lower
quality of life than patients in the low disease activity or remission states.
• NICE considered that biologic therapies in RA should only be recommended for patients with
DAS28 > 5.1 not responding to prior intensive combination DMARD therapy.
• The role of biologic therapies for the treatment of patients with moderate disease activity likely
to be an important area of debate for future NICE review of recommendations for RA.
Abbreviations: DAS, disease activity score; DMARD, disease-modifying antirheumatic drug; RA, rheumatoid arthritis.
13Q&A
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