1. MATURA Patient Advisory Group (MPAG)
Launch meeting
11.00am – 11.20am: Welcome & Introductions led by Chair, Zoe Ide
11.20 – 11.50am: MATURA introduction: Prof Cos Pitzalis and Prof Anne Barton
11.50 – 12.10am: MATURA Patient Advisory Group (MPAG): Zoe Ide
12.10 – 12.30pm: Introduction to clinical trial (STRAP): Dr Frances Humby
Ask the Clinician
12.30 – 12.50pm: Patient and Public Involvement and Engagement for MATURA:
Debbie Maskell (on behalf of Kanta Kumar)
How to engage / involvement
12.50 – 1.30pm: Any other business
Q&A
Next meeting date
Lunch provided during the meeting

2. MATURA Patient Advisory Group (MPAG)
Launch meeting
11.00am – 11.20am: Welcome & Introductions led by Chair, Zoe Ide
11.20 – 11.50am: MATURA introduction: Prof Cos Pitzalis and Prof Anne Barton
11.50 – 12.10am: MATURA Patient Advisory Group (MPAG): Zoe Ide   
12.10 – 12.30pm: Introduction to clinical trial (STRAP): Dr Frances Humby
Ask the Clinician
12.30 – 12.50pm: Patient and Public Involvement and Engagement for MATURA:
Debbie Maskell (on behalf of Kanta Kumar)
How to engage / involvement
12.50 – 1.30pm: Any other business
Q&A
Next meeting date
Lunch provided during the meeting

3. MATURA Patient Advisory Group (MPAG)
Launch meeting
Room B02/B03, Heart Centre, Charterhouse Square
Wednesday 10th December, 11am – 2pm
Costantino Pitzalis & Anne Barton (MATURA Co-Leads)

4. MATURA Patient Advisory Group (MPAG)
Launch meeting
OVERVIEW
Background:
Why do we need stratified medicine in RA?
MATURA Goals
MATURA & M-PAG

5. Why do we need stratified medicine in the management of rheumatoid arthritis?
Question?
To improve patient care by rationalising therapeutic decision making through:
Move away from trial & error treatment practice to molecular pathology driven algorithms
Maximise therapeutic efficacy of current drugs
Develop novel drugs tailored to specific non-responder patient groups

6. Employment: the costs of RA
Time after diagnosis people stopped working as a result of their RA - Not employed as a result of RA
The impact and costs of early retirement are likely to become more significant in future years, as flexible retirement ages become more common and people have more opportunities to work beyond the age of 65.
Among the 229 people who had given up work or retired early because of their RA:
• over a quarter (28.4%) had had to stop working within one year of diagnosis, and over half (59%) within six years (Figure 6)
• over two thirds of respondents under the age of 55 said that they would like to return to work if they could find a suitable job that would accommodate their RA (56 out of 79, or 70.8%). Over a quarter of those aged between 55 and 64 said the same (30 out of 114, or 26.3%).

7. Standard Treatment Pathway
40% failure
40% failure
Methotrexate
Other DMARDs
Other Biologics
Anti-TNF
time
Toxicity, Disability
Quality of life

8. The Impact of Rheumatoid Arthritis
Can we afford to continue using Biologics on a “trial an error” basis?
£10K/pt/yr x 5000 new pt/yr
Problems with Biologics
Anti-TNF in MTX non-responders
A large proportion of patients still do not optimally respond.
Huge unmet need !!!
Response Rate
ACR20
ACR50
ACR70
Unmet
Clinical
Need
Patients (%)
INF + MTX (ATTRACT): Lipsky PE et al. N Engl J Med 2000; 343: 1594–1502
ADA + MTX (DE019): Keystone EC et al. Arthritis Rheum 2004; 50: 1400–1411
ETA + MTX: Weinblatt ME et al. N Engl J Med 1999; 340: 253–925
Equivalent data for the Newer Anti-TNFs,
Abatacept, Tocilizumab and Rituximab

9. Standard Treatment Pathway?
Anti-TNF ?
Tocilizumab
Methotrexate
Other DMARDs ?
Abatacept ? ?
Rituximab
Tofactitinib
Jak/STAT

10. The Impact of Rheumatoid Arthritis
The Problem
1% Population - 580,000 Rheumatoid Arthritis Patients in England
Direct Medical Costs to the NHS ~ £560 million/year
Sick leave and work-related disability costs £4.2 billion/year

11. The Promise of Stratified Medicine

12. MATURA Patient Advisory Group (MPAG)
Launch meeting
OVERVIEW
Background:
Why do we need stratified medicine in RA?
MATURA Goals
MATURA & M-PAG

13. MAximising Therapeutic Utility in Rheumatoid Arthritis
MATURA
MAximising Therapeutic Utility in Rheumatoid Arthritis
Nationwide consortium of academics, consultants and industry groups
Working together to improve patient care
Investigating blood and tissue biomarkers
to treat Rheumatoid Arthritis right, the first time.
Two work streams (WS):
WS1 based in Queen Marys investigating synovial tissue biomarkers within a clinical trial (STRAP).
WS2 based in Manchester, investigating genetic biomarkers from existing and new large nationwide blood collections.

14. MAximising Therapeutic Utility in Rheumatoid Arthritis
MATURA
MAximising Therapeutic Utility in Rheumatoid Arthritis
GOALS
Improve patient care:
Identify tissue/blood biomarkers that predict therapeutic response and/or toxicity
Implement a stratified medicines approach in Rheumatoid Arthritis
Maximise therapeutic efficacy of current drugs
To engage patients in this journey to include patient perspective and help us maximise benefits for end users
To work with academic and industry partners to develop new drugs & companion diagnostics
To evaluate the financial and time impact on NHS using health economics

15. MATURA Workstream 1 Workstream 2
Statistics/Health Economics
Pathobiology, which is the nature of the disease:
STRAP clinical trial: to compare synovial tissue and blood analysis from the STRAP clinical trial by:
Methotrexate
Anti-TNF
Rituximab
Tocilizumab
Genetics/Genomics:
Large scale blood based screening from nationwide studies
Data Analysis and model development
Characteristics from blood and tissue for stratified medicine
Study of genes and their activity
Study of products of the cells and their activity
Pioneer new technology to examine genes and cell products
Pathobiology /Imaging data

16. MATURA Patient Advisory Group (MPAG)
Launch meeting
OVERVIEW
Background:
Why do we need stratified medicine in RA?
MATURA Goals
MATURA & M-PAG

17. MPAG: MATURA Patient Advisory Group
Public and patient involvement:
The mission of MPAG is active consultation, listening to and involving patients and members of the public about their views on the MATURA strategy to ensure that we take on patients perspective to make our work meaningful
Advising on PPI plans as they progress, e.g. qualitative research project
Feedback on dissemination methods, e.g. newsletters, website, reports, lay summaries.

18. MATURA TIMELINE FOR MPAG
Review MATURA Website
GRANT START
1/2015
STRAP
OPENS
3/3/2014
GRANT END
2/3/2018
2014
2015
2016
2017
2018
Today
Recruit
Staff
Study set up
Clinical Trial Initiation & Recruitment/Blood Collections
KEY
MPAG Meetings
MATURA ongoing
MPAG Specific time points
Initial Data Generation
MATURA strategy review &
recruitment update
Four or 5 key points.
This slide describes milestones related to strap either alone or as ws1 and ws2 analysis as marked in blue
We have already made headway in achieving critical tasks in advance of time points set in the grant for example we have revised ms 2.1 which commenced before the grant started and we are aiming to open the STRAP trial in October 2014
Subsequently we will be working to open all sites by the end of December 2014.
Throughout the 24 month recruitment period we will be working with partners to achieve the necessary recruitment targets. The number of participants are 4 after 6 months, 8-12 after 12 months and after 24 months
My job as PM is to have oversight of these timelines and I will be here to assist in achieving these goals.
Feedback Interim Analysis
Progress updates
Review of
economic savings
Newsletter

19. Stratification of Biologic Therapies for RA by Pathobiology
(STRAP trial)
A randomised, open-label biopsy-driven stratification trial in DMARD inadequate responder patients randomised to Etanercept, Tocilizumab or Rituximab
MRC (WS1 of the MATURA Consortium)
Funder
Queen Mary University of London
Sponsor
207 patients (DMARD ir)
Recruitment
Open label randomised control trial
Mandatory baseline synovial biopsy for stratification
Trial Design
48 weeks
Follow-up Duration
Rituximab (iv), Tocilizumab (sc) - Roche
Etanercept (sc) - Pfizer
Investigation Medicinal Products

20. Blood based sampling Anti TNF samples Methotrexate samples
Programme of work
Blood based sampling
Anti TNF samples
Methotrexate samples
Rituximab samples
Genetics
Epigenetics (partial funding)
Proteomics (pilot funding)
Transcriptomics (unfunded)
Integrated Analysis
The work stream 2 programme is based around blood sampling, processing and subsequent analysis integrated with the “omic” cross cutting themes. We have existing cohorts of samples and are planning new collections of samples which will then be analysed and integrated to answer the main scientific questions from our analysis plan, which you will hear about from Paul this afternoon.

21. Existing/new WS1 and WS2 blood sample cohorts
MTX Cohort
Early Arthritis
n=500 – collected
Selecting
patients
Genetic/genomic analysis to be carried out in Manchester
RNA-sequencing
Anti TNF Cohort
Early Arthritis
n=500 - collected
Integrated Analysis
Proteomic
analysis
RTX Cohort
n=1200
collection started
From the BRAGGSS study we have identified over 1000 samples already that have treatment response data and DNA available for genotyipng. Through the MATURA funding, we have identified a cohort of 540 DNA samples and we are currently genotyping these using the Illumina Human Core Exome SNP chip. We have completed 200 and expect the rest to be completed in the next few weeks. Within this cohort of 540 we already have epigenetic methylation data on 140 patients and of those 140, we have transcriptomic data on half again and so already we can start to integrate all this data within MATURA and if initial results are encouraging then it would be really exciting to have the potential (with additional funding) to generate further data from existing cohorts. Again, Paul will show this his analysis plan.
Deep immunological phenotyping on going at QMUL

22. Thank you Summary MATURA: Tackling a major unmet need in RA
MATURA: Opportunity to transform patients care
MPAG: Opportunity to meaningfully engage
MPAG: Opportunity to help inform strategy to make MATURA achievable
Thank you

23. MATURA Patient Advisory Group (MPAG)
Launch meeting
11.00am – 11.20am: Welcome & Introductions led by Chair, Zoe Ide
11.20 – 11.50am: MATURA introduction: Prof Cos Pitzalis and Prof Anne Barton
11.50 – 12.10am: MATURA Patient Advisory Group (MPAG): Zoe Ide   
12.10 – 12.30pm: Introduction to clinical trial (STRAP): Dr Frances Humby
Ask the Clinician
12.30 – 12.50pm: Patient and Public Involvement and Engagement for MATURA:
Debbie Maskell (on behalf of Kanta Kumar)
How to engage / involvement
12.50 – 1.30pm: Any other business
Q&A
Next meeting date
Lunch provided during the meeting

24. MATURA Patient Advisory Group (MPAG)
Launch meeting
11.00am – 11.20am: Welcome & Introductions led by Chair, Zoe Ide
11.20 – 11.50am: MATURA introduction: Prof Cos Pitzalis and Prof Anne Barton
11.50 – 12.10am: MATURA Patient Advisory Group (MPAG): Zoe Ide   
12.10 – 12.30pm: Introduction to clinical trial (STRAP): Dr Frances Humby
Ask the Clinician
12.30 – 12.50pm: Patient and Public Involvement and Engagement for MATURA:
Debbie Maskell (on behalf of Kanta Kumar)
How to engage / involvement
12.50 – 1.30pm: Any other business
Q&A
Next meeting date
Lunch provided during the meeting

25. MATURA Patient Advisory Group (MPAG)
Launch meeting
11.00am – 11.20am: Welcome & Introductions led by Chair, Zoe Ide
11.20 – 11.50am: MATURA introduction: Prof Cos Pitzalis and Prof Anne Barton
11.50 – 12.10am: MATURA Patient Advisory Group (MPAG): Zoe Ide   
12.10 – 12.30pm: Introduction to clinical trial (STRAP): Dr Frances Humby
Ask the Clinician
12.30 – 12.50pm: Patient and Public Involvement and Engagement for MATURA:
Debbie Maskell (on behalf of Kanta Kumar)
How to engage / involvement
12.50 – 1.30pm: Any other business
Q&A
Next meeting date
Lunch provided during the meeting

26. Qualitative Research Background
MATURA aims – stratified medicine
Patient views:
Stratified medicine
Diagnostic techniques
Risk/Benefit ratio
Qualitative research – asking the right questions, ultimately to inform a patient survey on acceptable risk/benefit ratios.

27. Focus group interviews
We aim to conduct interviews with patients to obtain their views on their;
Willingness to accept predictive testing
Preference to different tests
Information desired by patients at the time of undergoing the tests
Development of an interview topic guide

28. Your valuable support Development of an interview topic guide
We are seeking 2-3 MPAG members
Help inform the interview topic guide
This topic guide will contain questions that will assist us on having an open discussion around patients’ views about predictive testing
The agreed topic guide will be used during the interview

29. Working team
You will work closely with one of our experienced research team member: Kanta Kumar – Nurse Specialist and a Lecturer
She will hold approximately two meetings to talk to you about the interview guide and sort of questions that will be included

30. If you are interested… Please contact us on
Kanta Kumar:
Tel:
Debbie Maskell:
Tel:

31. MATURA Patient Advisory Group (MPAG)
Launch meeting
11.00am – 11.20am: Welcome & Introductions led by Chair, Zoe Ide
11.20 – 11.50am: MATURA introduction: Prof Cos Pitzalis and Prof Anne Barton
11.50 – 12.10am: MATURA Patient Advisory Group (MPAG): Zoe Ide   
12.10 – 12.30pm: Introduction to clinical trial (STRAP): Dr Frances Humby
Ask the Clinician
12.30 – 12.50pm: Patient and Public Involvement and Engagement for MATURA:
Debbie Maskell (on behalf of Kanta Kumar)
How to engage / involvement
12.50 – 1.30pm: Any other business
Q&A
Next meeting date
Lunch provided during the meeting