TY  - JOUR
AV  - public
IS  - 11
SN  - 0028-3878
A1  - Chataway, J
A1  - Martin, K
A1  - Barrell, K
A1  - Sharrack, B
A1  - Stolt, P
A1  - Wraith, D
A1  - for the ATX-MS 1467 Study Group
N2  - Objective: To assess safety, tolerability and efficacy of the antigen-specific immunotherapy ATX-MS-1467 in participants with relapsing multiple sclerosis (RMS) using different treatment protocols to induce tolerance.
Methods: Two open-label trials in adult participants with RMS. Study 1 was a multicentre Phase 1b safety evaluation comparing intradermal (i.d., Cohort 1) with subcutaneous (Cohort 2) administration in 43 participants. Both cohorts received ATX-MS-1467 dosed at 25, 50, 100, 400, and 800 ?g at 14-day intervals over 8 weeks, followed by 8 weeks with 4 additional 800 ?g doses at 14-day intervals and 32 weeks off study medication. Study 2 was a Phase 2a, multicentre, single-arm, trial enrolling 37 participants. ATX-MS-1467 was titrated from 50 痢 i.d. on Day 1 to 200 痢 on Day 15 and 800 痢 on Day 29 followed by biweekly administration of 800 ?g for 16 weeks and 16 weeks off study medication. Efficacy was evaluated on MRI parameters and clinical variables. Safety end points included treatment-emergent adverse events and injection-site reactions.
Results: In Study 1 there was a significant decrease in new/persisting T1 GdE lesions in Cohort 1 from baseline to Week 16, returning to baseline values at week 48. In Study 2, the number of T1 GdE lesions were significantly reduced on treatment and remained reduced at study completion. Safety results were unremarkable in both studies.
Conclusion: Relatively slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions and a sustained effect post-treatment. Further trials of ATX-MS-1467 are warranted.

Classification of Evidence: This work provides Class IV evidence that for patients with relapsing multiple sclerosis, slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions.
KW  - All Clinical trials
KW  -  Multiple sclerosis
KW  -  Class III
PB  - American Academy of Neurology
JF  - Neurology
VL  - 90
TI  - Effects of ATX-MS-1467 immunotherapy over 16 weeks in relapsing multiple sclerosis
N1  - This version is the version of record. For information on re-use, please refer to the publisher?s terms and conditions.
ID  - discovery10040441
UR  - https://doi.org/10.1212/WNL.0000000000005118
Y1  - 2018/03/13/
ER  -