Post ECTRIMS: Progressiv multippel sklerose Stamcelletransplantasjon

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1 Post ECTRIMS: Progressiv multippel sklerose Stamcelletransplantasjon Lars Bø Nasjonal kompetansetjeneste for multippel sklerose Nevrologisk avdeling, Haukeland universitetssjukehus Klinisk institutt 1, Universitetet i Bergen

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5 Howell OW et al. Brain 2011;134:

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14 Hawker K et al. OLYMPUS trial group. Ann Neurol Oct;66(4):

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22 Non-myeloablative hematopoietic stem cell transplantation (HSCT) is superior to disease modifying drug (DMD) treatment in highly active Relapsing Remitting Multiple Sclerosis (RRMS): interim results of the Multiple Sclerosis International Stem cell Transplant (MIST) Randomized Trial (S36.004) Richard K. Burt, Roumen Balabanov, John A. Snowden, Basil Sharrack, Maria Carolina Oliveira, Joachim Burman Neurology April 10, 2018; 90 (15 Supplement) April 25, 2018 Design/Methods: The primary endpoint was treatment failure defined as an increase in EDSS, assessed by a blinded evaluating neurologist, by at least 1.0 point sustained for at least 6 months. Patients on DMDs who failed after at least 1 year of treatment were allowed to crossover to HSCT.

23 Age between18-55 Diagnosis of MS using revised McDonald criteria of clinically definite MS (Appendix I). An EDSS score of 2.0 to 6.0 Inflammatory disease despite treatment with standard disease modifying therapy including at least 6 months of interferon or copaxone. Inflammatory disease is defined based on both MRI (gadolinium enhancing lesions) and clinical activity (acute relapses *treated with IV or oral high dose corticosteroids and prescribed by a neurologist). Minimum disease activity required for failure is defined as: a) two or more *steroid treated clinical relapses with documented new objective signs on neurological examination documented by a neurologist within the year prior to the study, or b) one *steroid treated clinical relapse within the year prior to study and evidence on MRI of active inflammation (i.e., gadolinium enhancement) within the last 12 months on an occasion separate from the clinical relapse (3 months before or after the clinical relapse). A steroid treated relapse will include a relapse that was severe enough to justify treatment but due to patient intolerance of steroids, or a history of non-response to steroids, they were offered but not used.

24 Results 110 patients were randomized, 55 to each arm. Three HSCT patients were withdrawn: two for failing enrollment criteria, one for recurrent infections occurring before transplant. Five control patients were withdrawn after soliciting transplants at other centers. No deaths occurred and no CTC grade 4 non-hematopoietic toxicities occurred in the transplant arm. DMDs (number of patients) used in the control arm were: natalizumab (22), dimethyl fumerate (18), fingolimod (13) interferons (10), glatiramer acetate (8), and mitoxantrone (5). Other immune drugs used in the control arm were corticosteroids (39), cyclophosphamide (2) and rituximab (2). With a mean follow up of 3 years (range 1 to 5 years), treatment failure was 60% (30 of 50) for control arm and 6% (3 of 52) for HSCT (P < 0.001). During the first year after HSCT, mean EDSS improved from 3.5 to 2.4 while it worsened from 3.3 to 3.9 in the control arm (P<0.001).

25 RAM-MS: Inklusjonskriterier Alder: RRMS etter reviderte McDonald kriterier EDSS 0 til 5.5 Signifikant betennelsesaktivitet tross forebyggende MS-behandling

26 RAMMS Hvem kan inkluderes i studien: MS-betennelse under behandling: Ett eller flere MS-attakk sisteår og 1 eller flere kontrastladende lesjon(er) eller 3 eller flere nye eller forstørrede T2 lesjoner siste år under behandling med immunmodulerende medikamenter

27 Inklusjonskriterier Attakket/attakkene må ha opptrådt 3 eller flere måneder etter oppstart med immunmodulerende medikament

28 EFFEKTMÅL Primært effektmål: Andel av pasienter med ingen tegn til ny sykdomsaktivitet (NEDA) over 2 år (104 uker) Planlagt studieforlenging: Andel av pasienter med NEDA over 5 år (260 uker).

29 Takk!