Escalation Treatment with Methylprednisolone Versus Immunoadsorption in MS Relapse: Results of the EMMA Trial
Florian Then Bergh1, Nicole Koeppe-Bauernfeind2, Clemens Goedel1, Achim Berthele3, Clemens Warnke5, Muriel Stoppe1, Claudius Kuechle4, Martin Spaeth6, Annegret Franke2
1University of Leipzig, Klinik u. Poliklinik fuer Neurologie, 2University of Leizig, Clinical Trial Centre, 3Neurology, 4Nephrology, School of Medicine, Technical University Munich, Klinikum rechts der Isar, 5Klinik Fuer Neurologie, University of Cologne, 6Nephrology, Klinik II Fuer Innere Medizin, University of Cologne
Objective:
To demonstrate superior efficacy of immunoadsorption (IA) over double-dose intravenous methylprednisolone (dd-IVMP) as escalated relapse treatment in multiple sclerosis (MS).
Background:
MS relapse is treated by IVMP. If symptoms persist, escalated treatment with dd-IVMP and eventually plasma exchange or IA is recommended, in the absence of randomized trials.
Design/Methods:
Publicly funded randomized, evaluator-blinded trial, including patients with persisting ADL impairment from an acute MS relapse with duration ≤28 days, and ≥7 days after receiving 2,500-3,000mg of IVMP. Randomization (1:1) to five sessions IA or cumulative 10,000mg IVMP. Primary outcome was the EDSS on day 45, analyzed by ANCOVA using baseline EDSS and stratification criteria as covariates.
Results:
Site initiation began in December 2019. During the Covid-19 pandemic, recruitment remained far behind schedule; organizational factors at the participating centers, non-competitive public funding, off-label IA treatment outside of clinical trials, and probably decreasing relapse rates persistently hampered recruitment even after the end of the pandemic. Therefore, recruitment had to be closed prematurely in June 2024. Until last safety data cutoff in May 2024, 29 patients had been randomized (f/m 22/7; mean age 32.9+/-10.6 yrs; 48% optic neuritis; median EDSS 5.5). Of these, 15 received IA, and 14 dd-IVMP. Three SAEs had occurred in the IA arm (syncope leading to concussion; pulmonary embolism with cough; anaphylactic reaction); all resolved without sequelae, and none of three dropouts was related to an SAE. Treatment response will be evaluated after database lock in Q1/2025, and results will be reported at the meeting.
Conclusions:
IA or dd-IVMP are feasible options in MS relapse with insufficient response to a first course of IVMP. Safety was consistent with known risks; treatment response will be reported, while the trial is clearly underpowered. In addition to clinical factors, insufficient public funding has contributed to premature termination of another investigator-initiated trial.
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