Efficacy and safety of alemtuzumab versus fingolimod in RRMS after natalizumab cessation.
BACKGROUND
Natalizumab (NTZ) was the first approved monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite proven and sustained efficacy, its use is limited by the risk of progressive multifocal leukoencephalopathy (PML). Moreover, some patients show ongoing disease activity under NTZ, requiring a switch to another disease-modifying treatment (DMT). However, evidence regarding the optimal DMT for treatment of active RRMS after NTZ-cessation is still scarce.


OBJECTIVE
To evaluate efficacy and safety outcomes of ALEM vs FTY treatment after cessation of NTZ.


METHODS
We retrospectively identified patients at 12 German neurology centers and analyzed risks for disease activity, adverse events, disability progression, and treatment discontinuation.


RESULTS
195 patients were identified and 144 underwent final analysis (FTY: 101; ALEM: 42). The hazard ratio for clinical relapses was 2.24 favoring ALEM (95% CI 1.12-4.50; p = 0.015). The hazard ratio for adverse events was 7.78 (95% CI 1.04-57.95; p = 0.006) and 2.41 for MRI progression (95% CI 1.26-4.60; p = 0.004). The odds ratio for disability progression after 12 months was 4.84 (95% CI 1.74-13.47, p = 0.003). Differences remained after adjusting for possible confounders (e.g., age, sex, baseline disability, NTZ treatment duration, washout time).


CONCLUSION
Our findings indicated particular advantages of ALEM compared to FTY in patients stopping NTZ.
['Pfeuffer|Steffen|S|http://orcid.org/0000-0001-5171-4845', 'Schmidt|Rene|R|', 'Straeten|Frederike Anne|FA|', 'Pul|Refik|R|', 'Kleinschnitz|Christoph|C|', 'Wieshuber|Marinus|M|', 'Lee|De-Hyung|DH|', 'Linker|Ralf A|RA|', 'Doerck|Sebastian|S|', 'Straeten|Vera|V|', 'Windhagen|Susanne|S|', 'Pawlitzki|Marc|M|', 'Aufenberg|Christoph|C|', 'Lang|Michael|M|', 'Eienbroeker|Christian|C|', 'Tackenberg|Björn|B|', 'Limmroth|Volker|V|', 'Wildemann|Brigitte|B|', 'Haas|Jürgen|J|', 'Klotz|Luisa|L|', 'Wiendl|Heinz|H|', 'Ruck|Tobias|T|', 'Meuth|Sven G|SG|']
D000328:Adult D000074323:Alemtuzumab D018450:Disease Progression D005260:Female D000068876:Fingolimod Hydrochloride D006801:Humans D007155:Immunologic Factors D056747:Immunomodulation D008297:Male D008875:Middle Aged D020529:Multiple Sclerosis, Relapsing-Remitting D000069442:Natalizumab D012189:Retrospective Studies D016896:Treatment Outcome
Alemtuzumab Fingolimod Natalizumab Progressive multifocal leukoencephalopathy Immunomodulatory therapy Remitting-relapsing multiple sclerosis