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ENCA 2016 - Genoa - Lucy R Wedderburn


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Exciting developments  : how to choose the right medicine in JIA and how to predict response to the treatment.

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ENCA 2016 - Genoa - Lucy R Wedderburn

  1. 1. Exci%ng  developments  :  how  to  choose   the  right  medicine  in  JIA  and  how  to   predict  response  to  the  treatment.     Lucy R Wedderburn Professor of Paediatric Rheumatology, Director, Arthritis Research UK Centre for Adolescent Rheumatology UCL GOS Institute for Child Health PReS ENCA meeting Genoa Italy September 2016
  2. 2. Disclosures: •  Pfizer  led  symposium  PRES  2016     •  Contribu%ons  to  CHART-­‐JIA  Consor%um  –    Janssen,   Pfizer  and  Roche   •  Abbvie     –  Expert  Panel  on  JIA     –  Support  for  mee%ng  London,  March  2016    
  3. 3. “JIA” is an umbrella term oligo     persistent   poly   RF+ve   ERA   psoria%c   systemic   poly     RF-­‐ve   Oligo   extended   JIA: •  Affects 1 in 1000 children •  Starts before age of 16 yr •  Arthritis in one or more joint for > 6 weeks •  Of no known cause
  4. 4. Immune  cells  
  5. 5. An%-­‐TNF   An%-­‐IL-­‐6   An%-­‐  IL-­‐1   An%-­‐CD20   The ‘arsenal’ of inflammation
  6. 6. Drug  name Trade  name Type  of  molecule Target Etanercept Enbrel Soluble  p75  TNF  receptor,  as   fusion  protein  to  Ig TNFa Infliximab Remicade Monoclonal  Ab  to  TNF,  chimeric TNFa Adalimumab Humira Monoclonal    Ab  to  TNF,   humanised TNFa Anakinra Kineret Human  receptor  antagonist   IL-­‐1Ra IL-­‐1 Canakinumab Ilaris Monoclonal    Ab  to  IL-­‐1,   humanised IL-­‐1 Tocilizumab Roactemra Monoclonal    Ab  to  IL-­‐6R,   humanised Il-­‐6 Rituximab Rituxan Monoclonal  Ab  to  CD20,   chimeric B  cells Abatacept Orencia Human  CTLA4  as  fusion  protein   (CTLA4-­‐Ig) CD80/86
  7. 7. Quality of  life Toxicity,  disability Time Fail DRUG  A DRUG  B Fail Fail DRUG  C DRUG  D Genotype RESPONDERS Variation in response to medication
  8. 8. How  can  we  switch  off  the  arthri%s  ?    
  9. 9. The example of systemic JIA   1990s  blood  serum  IL-­‐6    and  IL-­‐1  are    high  in  sJIA     2000s  a  drug  to  block  an%  IL-­‐6  is  available   2005,  2008:  an%  IL-­‐6    effec%ve  in  sJIA     2012  big  study  of  an%-­‐IL6R  in  sJIA   Approval  for  an%  IL-­‐6    therapy   Now  widely  in  use  in  sJIA…       Rooney  et  al  1995    
  10. 10. Problem: not all children with sJIA need Tocilizumab, not all respond to Tocilizumab, some need Anakinra, some get MAS
  11. 11. How  can  we  switch  off  the  arthri%s  ?     BLOOD JOINT IL-­‐17  making  cells   Healthy    Arthri%s    Arthri%s                                        blood              joint     Nistala  et  al  Arth  and  Rheum  2008  
  12. 12. Extended-to-be JIA: predicting how the arthritis will develop from the joint fluid
  13. 13. Extended-to-be JIA: predicting how the arthritis will develop from the joint fluid Hunter  et  al,  Arthri%s  and  Rheum,    2010   severe (extended) Oligo- Articular arthritis One year Diagnosis Outcome Sample mild (persistent)
  14. 14. Extended-to-be JIA: can we predict how the arthritis will develop from the joint fluid Persistent Extended-to-be 0 +2.7-2.7 Genes expressed Hunter  et  al,  Arthri%s  and  Rheum,    2010   p e r s i s t e n t e x t e n d e d - t o - b e 0 . 0 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 Ratio CD8:4 cells
  15. 15. How can we predict response ? JIA   Predict   response  to     treatment   Start   drug   Predict  effect   of  stopping   treatment   Measure   response  
  16. 16. The   use   of   tools   or   biomarkers   to   group   pa%ents   by   chance   of   responding   to   a   treatment   or   medicine,   chance   of   a   side   effect,   or   mechanism   of   disease,   to   help   decide  treatment  choice   Stratified medicine
  17. 17. What makes a good biomarker for predicting response to treatment •  Reliably  predicts  the  future     •  Easy  to  measure     •  Available  without  causing  upset  to  child   •  Economical    to  test    
  18. 18. How can we progress towards stratified medicine ? 6 (4-8)0 months   Start drug Data, sample Data, sample Define  response:     …..  Offer  the  chance  to  be  in  research  to  all  families    
  19. 19. Biomarkers in serum for JIA: prediction of flare after stopping MTX Foell  et  al,    J  Amer  Med  Assn  2010     Outcome after stopping MTX MRP8/14serumlevelbeforestoppingMTX
  20. 20. Biomarkers  in  serum  for  JIA:  predic%on  of  response   S100A8/A9 ( MRP8/14) (ng/ml) NR/ACR30 ACR50/ACR70 An%-­‐TNF   Moncrieffe  et  al,  Rheumatology    2013;     Anink  et  al,  Arth  Res  Therapy,    2015    
  21. 21. Stratified medicine in JIA in the UK ! CHildhood Arthritis Response to Treatment Consortium Childhood   arthri%s   prospec%ve  study     CHARMS   Childhood  arthri%s   response  to   medica%on  study  
  22. 22. Stratified medicine meeting in JIA, 2016 !CHildhood Arthritis Response to Treatment Consortium CARRA   Pharmachild   PRCSG   PRINTO   CCHMC   BIKER   Jumbo   ReachOut   CAPRI   Clarity     CHARMS   CAPS   BCRD   BSPAR  Etanercept  Study     25 World  experts  from     17 ins%tu%ons  and     18 8  countries   including  the  following   studies………………    
  23. 23. What do we need to achieve stratified medicine 1. Family  and  pa%ent  voice  is  KEY  !     2. All  children  need  to  have  standardised  data  collected   3. Agree  upon  targets  of  treatment  (subtype  specific)   4. Parallel  specimens  stored  where  possible     5. Trials  to  include  bio-­‐specimens  pre  drug     6. Strong  interna%onal  collabora%ons    
  24. 24. THANK  YOU  for   listening  and  lets   discuss    !