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006 Comparison of multiple disease modifying therapies in multiple sclerosis with marginal structural models
  1. Ibrahima Diouf1,
  2. Charles B Malpas1,2,
  3. Sifat Sharmin1,2,
  4. Olga Skibina3,4,5,
  5. Katherine Buzzard4,
  6. Jeannette Lechner-Scott6,7,
  7. Michael Barnett8,
  8. Suzanne Hodgkinson9,
  9. Mark Slee10,
  10. Ernest Butler11,
  11. Pamela McCombe12,13,
  12. Anneke van der Walt4,14,
  13. Helmut Butzkueven15,
  14. Steve Vucic16,
  15. Richard Macdonell15,
  16. Cameron Shaw17 and
  17. Tomas Kalincik1,2
  1. 1CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
  2. 2MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia
  3. 3Department of Neurology, Box Hill Hospital, Melbourne, VIC, Australia
  4. 4Monash University, Melbourne, VIC, Australia
  5. 5The Alfred Hospital, Melbourne, Australia
  6. 6School of Medicine and Public Health, University Newcastle, Newcastle, NSW, Australia
  7. 7Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, NSW, Australia
  8. 8Brain and Mind Centre, Sydney, Australia
  9. 6Liverpool Hospital, Sydney, NSW, Australia
  10. 9Liverpool Hospital, Sydney, NSW, Australia
  11. 10Flinders University, Adelaide, SA, Australia
  12. 11Monash Medical Centre, Melbourne, VIC, Australia
  13. 12University of Queensland, Brisbane, QLD, Australia
  14. 13Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia
  15. 14Department of Neurology, The Alfred Hospital, Melbourne, VIC, Australia
  16. 15Austin Health, Melbourne, VIC, Australia
  17. 16Westmead Hospital, Sydney, NSW, Australia
  18. 17Geelong Hospital, Geelong, VIC, Australia


Background Because of methodological challenges comparisons of multiple treatments in multiple sclerosis cohorts have been limited to pairwise and triple comparisons.

Objectives Extend marginal structural models (MSM) to allow simultaneous comparisons of multiple MS treatments.

Methods We selected patients from the MSBase registry with Clinically Isolated Syndrome and Relapsing-Remitting MS followed for ≥1 year, with ≥3 visits, ≥1 visit per year and exposed to a MS therapy. MSMs were used to compare cumulative hazards of 6-month confirmed worsening and improvement of disability, and the incidence of relapses between treatments. MSMs were continuously re-adjusted for patient age, sex, pregnancy, date from first symptom, prior relapse history and MRI activity. We used MSMs to compare the Average Treatment Effect (ATE), the effect a treatment would have had if the entire study population had been treated with this treatment vs. another treatment. We also estimated the Average Treatment Effect Among the Treated (ATT): comparison an observed effect of a treatment with a counterfactual (not observed) effect of another treatment in the same study population.

Results Among 23687 patients, we compared ATE of glatiramer acetate (reference), interferon b, natalizumab, fingolimod, dimethyl fumarate, and teriflunomide. In ATE, a reduction of relapse frequency was more prominent on natalizumab, followed by fingolimod (47% and 24% respectively, reference: glatiramer acetate) when compared with the other treatments. The ATT models confirmed these observations.

Conclusions Compared to other DMTs natalizumab and fingolimod were associated with superior reduction in relapse frequency than glatiramer acetate, interferon beta, teriflunomide and dimethyl fumarate.

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