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:

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&ANext meeting date Lunch provided during the meeting

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)


• Background: • Why do we need stratified medicine in RA?

• MATURA Goals• MATURA & M-PAG

OVERVIEW

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

Why do we need stratified medicine in the management of rheumatoid arthritis?

Time after diagnosis people stopped working as a result of their RA - Not employed as a result of RA

Employment: the costs of RA

Standard Treatment Pathway

MethotrexateOther DMARDs Anti-TNF

Other Biologics

40% failure

40% failure

Quality of lifeToxicity, Disability

time

A large proportion of patients still do not optimally respond.Huge unmet need !!!

Problems with Biologics

Can we afford to continue using Biologics on a “trial an error” basis?

£10K/pt/yr x 5000 new pt/yr

The Impact of Rheumatoid Arthritis

Anti-TNF in MTX non-responders

INF + MTX (ATTRACT): Lipsky PE et al. N Engl J Med 2000; 343: 1594–1502ADA + MTX (DE019): Keystone EC et al. Arthritis Rheum 2004; 50: 1400–1411ETA + MTX: Weinblatt ME et al. N Engl J Med 1999; 340: 253–925

Equivalent data for the Newer Anti-TNFs,Abatacept, Tocilizumab and Rituximab

ACR20

ACR50

ACR70

Unmet Clinical Need

Patie

nts

(%)

Response Rate

Rituximab

Abatacept

Tocilizumab

Anti-TNF

Tofactitinib

Jak/STAT

????

Standard Treatment Pathway

MethotrexateOther DMARDs

?

• 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

The Problem

The Impact of Rheumatoid Arthritis

The Promise of Stratified Medicine

Drug Response Algorithm

Biom

arke

r

Appl

yAl

gorit

hm

DRUG A

DRUG B

DRUG C

DRUG D

Treat Right First Time




OVERVIEW

• 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. • 2014 - 2018

MATURAMAximising Therapeutic Utility in Rheumatoid Arthritis

1. 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

2. To engage patients in this journey to include patient perspective and help us maximise benefits for end users

3. To work with academic and industry partners to develop new drugs & companion diagnostics

4. To evaluate the financial and time impact on NHS using health economics

GOALS

MATURAMAximising Therapeutic Utility in Rheumatoid Arthritis

MATURA

Genetics/Genomics: Large scale blood based

screening from nationwide studies

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

Data Analysis and m

odel development

Characteristics from blood and tissue for stratified m

edicine

Study of genes and their activity

Study of products of the cells and their activity

Pioneer new technology to examine genes and cell products

Workstream 1 Workstream 2Statistics/Health Economics

Pathobiology /Imaging data




OVERVIEW

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.

MATURA TIMELINE FOR MPAG

2014 2015 2016 2017 2018

Today

GRANT END

2/3/2018

STRAP OPENS

Review MATURA Website1/2015GRANT

START3/3/2014

Recruit Staff

Study set up

Clinical Trial Initiation & Recruitment/Blood Collections

Initial Data Generation

MATURA strategy review & recruitment update

Feedback Interim Analysis

Progress updates

Review of economic savings

Newsletter

KEY

MPAG Meetings

MATURA ongoing

MPAG Specific time points

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 LondonSponsor

• 207 patients (DMARD ir)Recruitment

• Open label randomised control trial• Mandatory baseline synovial biopsy for stratificationTrial Design

• 48 weeksFollow-up Duration

• Rituximab (iv), Tocilizumab (sc) - Roche• Etanercept (sc) - Pfizer

Investigation Medicinal Products

Blood based sampling

Anti TNF samples

Methotrexate samples

Rituximab samples

Genetics

Epigenetics (partial funding)

Proteomics (pilot funding)

Transcriptomics (unfunded)

Programme of work

Inte

grat

ed

Anal

ysis

Existing/new WS1 and WS2 blood sample cohorts

MTX CohortEarly Arthritis

n=500 – collected

Selectingpatients

Inte

grat

ed

Anal

ysis

RNA-sequencing

Proteomic analysis

Deep immunological phenotyping on going at QMUL

Genetic/genomic analysis to be carried out in Manchester

Anti TNF CohortEarly Arthritis

n=500 - collected

RTX Cohort n=1200

collection started

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













Qualitative Research Background MATURA aims – stratified medicinePatient 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.

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

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

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

If you are interested…

• Please contact us on• Kanta Kumar: [email protected]

Tel: 07904 507 726• Debbie Maskell:

[email protected] Tel: 0161 275 5046

mailto:[email protected]

mailto:[email protected]





Documents

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: