Objective:

To report the long-term clinical outcomes of TMS patients, comparing disease modifying therapeutic drug classes.

Background:

Tumefactive multiple sclerosis (TMS) is characterized by large demyelinating brain lesions, typically >2cm in diameter. Effective treatment approaches are uncertain.  

Design/Methods:

A retrospective cohort study of adults with TMS (2015-2023) at two Boston hospitals. Case files were reviewed by two MS neurologists. Immunosuppressive therapies were categorized into B-cell depleting therapy, other high-efficacy, and no/low/ medium-efficacy therapy. Outcomes of interest were the expanded disability status scale (EDSS) score at one year and last known follow up. 

Results:

67 patients had TMS (female 70.2%; White 83.6%, Asian 4.4%, Black 4.4%, median age 36 years; 95.5% newly MS diagnosed). 62 (92.5%) were treated with maintenance immunosuppressives (median time to initiation 137 days). Treatments were: B-cell depleting therapy (n=36, 21 on ocrelizumab, 13 on rituximab, 2 on ofatumumab); other high-efficacy therapy (n=6, 3 each on natalizumab and cyclophosphamide), and low/medium efficacy therapy (n=18, 9 on dimethyl fumarate, 2 each on glatiramer acetate, interferon-beta, mycophenolate mofetil, fingolimod and 1 on siponimod). One patient switched cyclophosphamide to glatiramer acetate and one from natalizumab to rituximab.

The mean EDSS was 3.3 (range 1.5-5.1) at TMS onset, 2.1 (range 1.0-2.8) at year one, and 2.5 (1.0-2.1) at last follow up (median 1270 days). Comparing mean EDSS scores, patients receiving non-B-cell high efficacy therapy did worse than with no treatment/low efficacy therapies (2.5, p value= 0.02) and B-cell therapy showed no difference compared to no treatment/low efficacy (-0.52, p-value=0.42) controlling for age and sex. A multilinear regression model found higher presentation EDSS and non-B-cell high efficacy therapies were associated with higher EDSS at last follow up.

Conclusions:

Non-B-cell high-efficacy therapy should likely be avoided in TMS. Further research, prospectively, is needed to confirm these findings, determine the value of B-cell therapies, and rule out reverse causation.