MS Disease-Modifying Therapy Discontinuation Associated With Disability Progression

Author(s):

DMT discontinuation resulted with new disability worsening and/or progression in previously stable patients with relapsing-remitting MS and particularly in patients with previously stable secondary progressive MS.

Dejan Jakimovski, MD, PhD

Newly published findings showed that following discontinuation of a disease-modifying therapy (DMT), more than one-third of patients with a stable disease course of multiple sclerosis (MS) experienced disability worsening/progression (DWP), with no clear relation to age or disease subtype.

Led by Dejan Jakimovski, MD, PhD, assistant research professor, Buffalo Neuroimaging Analysis Center, this longitudinal, retrospective analysis included 216 patients with MS who discontinued DMTs. They had clinical visits before, during, and after DMT use, referred to as time 1, time 2, and time 3, respectively, to assess changes in the clinical course.

From time 1 to time 2, patients who demonstrated no change in Expanded Disability Status Scale (EDSS) scores (<1.0 increase if EDSS <6.0, or <0.5-point increase if EDSS ≥6.0) were considered to have a stable disease course. From the cohort of those who discontinued DMT, 161 (72.5%) were classified as stable before discontinuation.

In the period after DMT discontinuation, 53 (32.9%) previously stable patients with MS experienced DWP, a significantly greater percentage than those that were already experiencing DWP before discontinuation (18.2%; X² test, P = .04).

After demonstrating a minor decrease in EDSS (time 1 to time 2 median EDSS: 3.5 vs 3.0; Wilcoxon Signed Rank test Z-score, –4.122; P <.001) at the time of discontinuation, patients with a stable disease course experienced a significant increase in EDSS after discontinuation of DMT (time 2 to time 3 median EDSS: 3.0 vs 3.5; Wilcoxon Signed Rank test Z-score, –5.37; P <.001). In comparison, the previously progressing MS patient group, which showed significant increase in EDSS at time of DMT discontinuation (time 1 to time 2 median EDSS: 4.5 vs 6.5; Wilcoxon Signed Rank test Z-score, 6.501; P <.001), had relatively stable EDSS scores (median 6.5 vs 6.5; Wilcoxon Signed Rank test Z-score, 0.687; P = .492).

There was no clear indication that this trend was specific to a single form of MS. In total, 31 (29.2%) of the 106 previously stable patients with relapsing-remitting MS (RRMS) had new DWP and 6 (20%) of the 30 patients with RRMS who had previous DWP had additional DWP. Furthermore, 22 (40%) of the 55 previously stable patients with secondary progressive MS (SPMS) had new DWP following discontinuation of DMT and only 4 (16%) of 25 already progressing patients with SPMS experienced DWP.

Of the 25 patients who transitioned to SPMS, 10 (40%) also experienced DWP after DMT discontinuation. In comparison, 27 (24.3%) of 111 patients that remained with RRMS experienced DWP after DMT discontinuation.

A secondary analysis was conducted for 81 patients with MS at least 55 years of age and 135 patients with MS who were below that. Although the older population had significantly longer disease duration (25.3 vs 13.9 years; Student’s t-test, P <.001), greater percentage of progressive phenotype of MS (X² test, P < 0.015 at all 3 visits) and were significantly more disabled before DMT discontinuation and at time of discontinuation, both groups demonstrated similar rates of DWP (before DMT discontinuation: 24.7% vs 25.9% [X²test, P = 0.873]; after DMT discontinuation: 25.9% vs 31.1% [X² test, P = 0.443]) from time 1 to time 2, and time 2 to time 3, respectively.

Prior to discontinuation of DMT, patients with EDSS scores of at least 6 were more likely to experience DWP than those with scores of less than 6 (40.7% vs 15.4%; X² test, P <.001). Similarly, this group also had a significantly higher number of patients with DWP after discontinuation of DMT compared with patients that had EDSS scores remain below 6 during the entire study period (time 1 to time 2: 39.6% vs 15.2% [X² test, P <.001]; time 2 to time 3: 37.4% vs 23.2% [X² test, P <.001]; time 1 to time 3: 56.0% vs 28.8% [X² test, P <.001]).

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REFERENCE

Jakimovski D, Kavak K, Vaughn CB, et al. Discontinuation of disease modifying therapies is associated with disability progression regardless of prior stable disease and age. Mult Scler Relat Disord. 2022;57: 103406. doi:10.1016/j.msard.2021.103406