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“Rheumatoid Arthritis
Too expensive to treat, too expensive to fail?
Iain B McInnes PhD, FRCP, FRSE, FMedSci
Professor of Medicine & Director,
Institute of Infection, Immunity and Inflammation,
University of Glasgow
Scotland, UK
From Whence We Have Come…
Used with permission from Scott DL, et al. Lancet. May 16 1987;1(8542):1108-1111. ©1987 Elsevier.
Disease duration: 1.5 years 5 years 15 years
SHARP score: 23 SHARP score: 56 SHARP score: 96
Rheumatoid arthritis – progressive damage
RA – the wider perspective?
Impact of RA
Patients  Pain, disability, co-morbidity and premature mortality
Health Care  Direct Costs ~ €14 Billion (Europe)1
– hospitalisation, treatment, diagnostics
Societal  Indirect Costs ~ €17 Billion (Europe)
– productivity and informal costs
– within 10 years of disease onset >50% of people  unable to work
Global drug market  $38.5 Billion in 20172
1. Lundkvist J et al. The burden of RA and access to treatment: health
burden and costs. Eur J Health Econ (2008) 8:49–60
2. Visiongain, April 2013. Rheumatoid Arthritis (RA): World Drug
Market 2013-2023
NSAIDs GC +DMARD
A pre-molecular history of arthritis management...
Willow (Salix) Johann Andreas
Buchner
SALICIN
1829 1948 1994
ACTH, MTX
7
Lessons from a decade: molecular hierarchies exist
Many vulnerable nodes in inflammatory cascade – cell receptors and their
requisite signalling pathways?
Cytokine-targeting biologics
APC
Cell-targeting biologics
Inhibition of
T-cell activation
Blocks co-stimulatory
signal
Abatacept
MHC
Antigen
T-cell receptor
T cell
CD28
Depletion
of B cells
Rituximab
CD20
B cell
Tocilizumab
Blockade of IL-6R
classic and trans
signalling pathways
Blockade of TNF
signalling pathways
Anti-TNFs
Extracellular
Intracellular
IL-1 TNF
Anti-IL-1s
AID, autoinflammatory disease including Still’s disease; CD, Crohn’s disease;
GCA, giant cell arteritis; IL, interleukin; JIA, juvenile idiopathic arthritis; RA, rheumatoid arthritis;
SpA, spondyloarthritis; TNF, tumor necrosis factor; UC, ulcerative colitis
Lessons from a decade:
Towards molecular taxonomy in inflammation medicine?
Schett G, McInnes IB et al. Nature Med 2013
McInnes IB et al Lancet 2015
9
Lessons about strategies?
‘Treat to target'… but ‘knowing when to stop?’
Adapted from Smolen JS et al (2015) Ann Rheum Dis doi:10.1136/annrheumdis-2015-207524
Therapeutic
taper
?
Drug-free
remission
Smolen J, Aletaha D & McInnes IB Lancet (2016): Smolen J & Aletaha D Nature Reviews Rheum (2015)
RA – pathogenesis and therapeutics?
11
Do we really need a personalised medicine
based approach?
Porter D et al Lancet 2016
12
To the future: Scottish Early RA Collaboration
1200
Scottish Nested Arthritis Progression Study
• >50 new RA
• Deep immune phenotyping
EU FP7: Masterswitch
BTCure, TEAM
University of Glasgow
Paul Garside
James Brewer
Carl Goodyear
Simon Milling
Mariola Kurowska-Stolarska
Gerard Graham
Derek Gilchrist
Neal Millar
Jagtar Nijjar Singh
Bill Ferrell
John Lockhart
Roger Sturrock
Hilary Capell
Foo Liew
Darren Asquith
Ashley Miillar
Aziza Elmesmari
James Reilly
Shauna Kerr
Lynn Stewart
Clare Tange
Axel Hueber
Bob Benson
Cat Prendergast
George Fragoulis
Catholic University of
the Sacred Heart, Rome
Stefano Alivernini
Giacoma Ferraccioli
ARUK Centre
John Isaacs
Chris Buckley
Marina Frleta
Lynn Stewart
Ashleigh Rainey
Clare Tange
Marina Frleta
Donna McIntyre
Derek Baxter
Brian Morton
Bernard Leung
Charles McSharry
Florian Meier
SERA
Duncan Porter
Stefan Siebert
Caron Paterson
Sharon Kean
Jane Hair
Ashley Gilmour
Carl Goodyear
Edinburgh University
Stuart H. Ralston
Aberdeen University
David Reid
Neil Basu
Janet Liversidge

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Rheumatoid Arthritis: Too expensive to treat, too expensive to fail

  • 1. “Rheumatoid Arthritis Too expensive to treat, too expensive to fail? Iain B McInnes PhD, FRCP, FRSE, FMedSci Professor of Medicine & Director, Institute of Infection, Immunity and Inflammation, University of Glasgow Scotland, UK
  • 2. From Whence We Have Come… Used with permission from Scott DL, et al. Lancet. May 16 1987;1(8542):1108-1111. ©1987 Elsevier.
  • 3. Disease duration: 1.5 years 5 years 15 years SHARP score: 23 SHARP score: 56 SHARP score: 96 Rheumatoid arthritis – progressive damage
  • 4. RA – the wider perspective?
  • 5. Impact of RA Patients  Pain, disability, co-morbidity and premature mortality Health Care  Direct Costs ~ €14 Billion (Europe)1 – hospitalisation, treatment, diagnostics Societal  Indirect Costs ~ €17 Billion (Europe) – productivity and informal costs – within 10 years of disease onset >50% of people  unable to work Global drug market  $38.5 Billion in 20172 1. Lundkvist J et al. The burden of RA and access to treatment: health burden and costs. Eur J Health Econ (2008) 8:49–60 2. Visiongain, April 2013. Rheumatoid Arthritis (RA): World Drug Market 2013-2023
  • 6. NSAIDs GC +DMARD A pre-molecular history of arthritis management... Willow (Salix) Johann Andreas Buchner SALICIN 1829 1948 1994 ACTH, MTX
  • 7. 7 Lessons from a decade: molecular hierarchies exist Many vulnerable nodes in inflammatory cascade – cell receptors and their requisite signalling pathways? Cytokine-targeting biologics APC Cell-targeting biologics Inhibition of T-cell activation Blocks co-stimulatory signal Abatacept MHC Antigen T-cell receptor T cell CD28 Depletion of B cells Rituximab CD20 B cell Tocilizumab Blockade of IL-6R classic and trans signalling pathways Blockade of TNF signalling pathways Anti-TNFs Extracellular Intracellular IL-1 TNF Anti-IL-1s
  • 8. AID, autoinflammatory disease including Still’s disease; CD, Crohn’s disease; GCA, giant cell arteritis; IL, interleukin; JIA, juvenile idiopathic arthritis; RA, rheumatoid arthritis; SpA, spondyloarthritis; TNF, tumor necrosis factor; UC, ulcerative colitis Lessons from a decade: Towards molecular taxonomy in inflammation medicine? Schett G, McInnes IB et al. Nature Med 2013 McInnes IB et al Lancet 2015
  • 9. 9 Lessons about strategies? ‘Treat to target'… but ‘knowing when to stop?’ Adapted from Smolen JS et al (2015) Ann Rheum Dis doi:10.1136/annrheumdis-2015-207524 Therapeutic taper ? Drug-free remission
  • 10. Smolen J, Aletaha D & McInnes IB Lancet (2016): Smolen J & Aletaha D Nature Reviews Rheum (2015) RA – pathogenesis and therapeutics?
  • 11. 11 Do we really need a personalised medicine based approach? Porter D et al Lancet 2016
  • 12. 12 To the future: Scottish Early RA Collaboration 1200 Scottish Nested Arthritis Progression Study • >50 new RA • Deep immune phenotyping
  • 13. EU FP7: Masterswitch BTCure, TEAM University of Glasgow Paul Garside James Brewer Carl Goodyear Simon Milling Mariola Kurowska-Stolarska Gerard Graham Derek Gilchrist Neal Millar Jagtar Nijjar Singh Bill Ferrell John Lockhart Roger Sturrock Hilary Capell Foo Liew Darren Asquith Ashley Miillar Aziza Elmesmari James Reilly Shauna Kerr Lynn Stewart Clare Tange Axel Hueber Bob Benson Cat Prendergast George Fragoulis Catholic University of the Sacred Heart, Rome Stefano Alivernini Giacoma Ferraccioli ARUK Centre John Isaacs Chris Buckley Marina Frleta Lynn Stewart Ashleigh Rainey Clare Tange Marina Frleta Donna McIntyre Derek Baxter Brian Morton Bernard Leung Charles McSharry Florian Meier SERA Duncan Porter Stefan Siebert Caron Paterson Sharon Kean Jane Hair Ashley Gilmour Carl Goodyear Edinburgh University Stuart H. Ralston Aberdeen University David Reid Neil Basu Janet Liversidge