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Switching to a second TNF-antagonist. Why not?

Switching to a second TNF-antagonist. Why not?. Emilio Martin Mola Hospital Universitario La Paz. Madrid.

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Switching to a second TNF-antagonist. Why not?

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  1. Switching to a second TNF-antagonist.Why not? Emilio Martin Mola Hospital Universitario La Paz. Madrid

  2. 750 Patients Treated with Rituximab for RA in European Registries: Baseline Data Analysis from the Collaborative European REgistries for Rituximab in RA (CERERRA). ACR 2009, San Francisco Czech R. Denmark, Finland, Netherlands, Norway, Slovenia, Spain, Sweden, Switzerland • 756 patients were included from 9 countries. • As expected, patients had long-standing, active RA, and had failed an average of 3 DMARDS. • 60% of patients had failed >2 anti-TNF agents • 28% had failed one. • 12% of patients were given RTX as their first biologic van Vollenhoven RF, ACR San Francisco 2009

  3. HAS: Haute Autorité de Santé. France Therapeutic strategy for a patient with inadequate response to an optimal dosage of methotrexate ≥ 3 months • Active or evolutive RA • with a DAS 28 score >5.1 • with a DAS 28 score >3.2 and long-term steroids (0.1–0.15 mg/kg/d) • with the presence or progression of structural lesions on radiography To prescribe according to the level of RA activity, age, comorbidities, wish of the patient MTX associated with a TNF blocker Failure If contra-indicated or safety concerns 2nd TNF blocker associated with DMARD Failure MTX associated with RTX or abatacept MTX associated with RTX or abatacept alternative 3rd TNF blocker associated with DMARD www.has-sante.fr

  4. Evidence for Switching to a second anti-TNF • Registers • Spanish • British • Others • Clinical Studies • React • Others • RCTs • Golimumab

  5. Retention Rates After SwitchingTNF Inhibitors 1.00 First TNF inhibitor 0.75 Second TNF inhibitor 0.50 Third TNF inhibitor 0.25 0 0 0.5 1.0 1.5 2.0 Years Gomez-Reino JJ, et al. Arthritis Res Ther 2006; 8: R29

  6. BSRBR(British Society for Rheumatology Biologics Register) Hyrich KL et al Arthritis and Rheum 2007;56:13-20

  7. The British Experience (RA) Outcome with second biologic agent. Mean followup 15 m Results:Overall, 73% of patients who switched to a second anti-TNF agent remained on the new therapy by the end of follow-up Conclusion:In conclusion, these data from a large unselected population of RA patients suggest that based on treatment continuation rates, there is a strong case for switching patients to a second anti-TNFα….. Hyrich KL et al Arthritis and Rheum 2007;56:13-20

  8. Evidence for Switching to a second anti-TNF • Registers • Spanish • British • Others • Clinical Studies • React • Others • RCTs • Golimumab

  9. ReAct Study Open-label conducted at 448 centers in Europe and Australia RA with DAS ≥3.2 despite standard anti-rheumatic treatment Prior TNF antagonists treatment allowed Adalimumab 40 mg eow for 12w. Extension optional 6,610 p. recruited, 889/6,610 prior treatment with Infliximab and/or Etanercept. RF (+) 72% ACR20 ACR50 ACR70 Good EULAR Moderate EULAR Bombardieri S et al. Rheumatology on line 2007

  10. ACR response according to the reason for TNF antagonist withdrawal ACR20 ACR50 ACR70 Moderate EULAR Good EULAR Bombardieri S et al. Rheumatology on line 2007

  11. Switching from INFLIXIMAB to ADALIMUMAB 24 RA who discontinued infliximab Treated with adalimumab 12 months Results compared with 25 matched-control -RA patients treated with adalimumab without previous TNF-antagonist treatment Clinical response after 12 months of adalimumab Nikas SN Ann Rheum Dis 2007; 65:257-60

  12. Evidence for switching to a second anti-TNF • Registers • Spanish • British • Others • Clinical Studies • React • Others • RCTs • Golimumab

  13. ACR20 at week 14 and 24 *P< 0.001 Smolen J et al. EULAR 2008

  14. Proportion of ACR20 responders at Week 14 by sub-groups Odds Ratio and 95% CIGolimumab Combined vs. Placebo Proportion of ACR20 Responders at Week 14 No. of prior TNF inhibitors 1 2 3 Reason for discontinuationof prior TNF inhibitor Lack of efficacy Non-efficacy related reasons 0.1 1 10 100 Golimumab CombinedBetter PlaceboBetter Smolen et al, at EULAR 2008. Permission given by J. Smolen

  15. Comparison of ACR 20/50/70 responses % patients * Without previous anti-TNF 1 previous anti-TNF 2 previous anti-TNF Abatacept (ATTAIN) 2 - 24 w. Rituximab (REFLEX) 3 - 24 w. Tocilizumab 8 mg/Kg (RADIATE) 4 - 24 w.- Golimumab 100 mg (GO-FORWARD) 5 - 24 w.- Adalimumab – 12 w. (REACT)1 1.- Bombardieri S, et al. Rheumatology (Oxford). 2007 ;46(7):1191-9. 2.- Genovese MC, et al. N Engl J Med. 2005 ;353(11):1114-23. 3.-Cohen SB, et al. Arthritis Rheum. 2006 ;54(9):2793-806. 4.- Emery P, et al. Ann Rheum Dis. 2008 ;67(11):1516-23. 5.- Smolen J, et al. Ann Rheum Dis 2008;67(Suppl II):50. *- Datos a 16 semanas: Kay J, et al. Arthritis Rheum. 2008 Apr;58(4):964-75.

  16. Why promoting the change to a second anti-TNF? • A second anti-TNF (golimumab) is effective • Even after 2 previous anti-TNF failures • Irrespective of the cause of withdrawal, i.e., inefficacy and AE • Works in all populations (RF and CCP positive & negative) • Response to TNF antagonists is faster ( ̴ 1-3 months) than with RTX • If doesn’t work there is time enough to switch to RTX

  17. With a second anti-TNF your patient has more opportunities… Evaluation 2nd anti-TNF If doesn’t work…switch 3-4 m evaluation If works…keep anti-TNF It works…keep RTX 3-4 m evaluation your patient lost an opportunity If doesn’t work… RTX

  18. If the switching with RTX fails… • We have: • An active patient with no B cells and… • One question • What’s next?

  19. Wimbledon 2007

  20. Wimbledon 2008 Give Always a Second Chance

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