Association of Disease-Modifying Treatment With Outcome in Patients With Relapsing Multiple Sclerosis and Isolated MRI Activity

Neurology. 2024 Sep 24;103(6):e209752. doi: 10.1212/WNL.0000000000209752. Epub 2024 Aug 28.

Abstract

Background and objectives: Isolated value of MRI metrics in relapsing multiple sclerosis (RMS) as a surrogate marker of response to disease-modifying treatment (DMT) and, thus, as decision criteria for DMT escalation in the absence of clinical signs of disease activity is still a matter of debate. The aim of this study was to investigate whether DMT escalation based on isolated MRI activity affects clinical outcome.

Methods: Combining data from 5 MS centers in Austria and Switzerland, we included patients with RMS aged at least 18 years who (1) had initiated first-line, low-to-moderate-efficacy DMT (interferon β, glatiramer acetate, teriflunomide, or dimethyl fumarate) continued for ≥12 months, (2) were clinically stable (no relapses or disability progression) on DMT for 12 months, (3) had MRI at baseline and after 12 months on DMT, and (4) had available clinical follow-up for ≥2 years after the second MRI. The primary endpoint was occurrence of relapse during follow-up. The number of new T2 lesions (T2L) and DMT strategy (continuing low-/moderate-efficacy DMT vs escalating DMT) were used as covariates in regression analyses.

Results: A total of 131 patients with RMS, median age of 36 (25th-75th percentiles: 29-43) years, 73% women, were included and observed over a median period of 6 (5-9) years after second MRI. Sixty-two (47%) patients had relapse. Patients who continued first-line DMT had a 3-fold increased risk of relapse given 2 new T2L (hazard ratio [HR] 3.2, lower limit [LL] of 95% CI: 1.5) and a 4-fold increased risk given ≥3 new T2L (HR 4.0, LL-CI: 2.1). Escalation of DMT lowered the risk of relapse in patients with 2 new T2L by approximately 80% (HR 0.2, upper limit [UL] of 95% CI: 1.3) and with ≥3 new T2L by 70% (HR 0.3, UL-CI: 0.8). In case of only 1 new T2L, the increased risk of relapse and the treatment effect did not reach statistical significance of 5%.

Discussion: In our real-world cohort of patients clinically stable under low-to-moderate-efficacy DMT, escalation of DMT based on isolated MRI activity decreased risk of further relapse when at least 2 new T2L had occurred.

Classification of evidence: This study provides Class III evidence that clinically stable patients with MS on low-/moderate-efficacy DMT with ≥3 new T2L on MRI who escalate DMT have a reduced risk of relapse and Expanded Disability Status Scale progression.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Austria
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Crotonates / therapeutic use
  • Dimethyl Fumarate / therapeutic use
  • Female
  • Follow-Up Studies
  • Glatiramer Acetate / therapeutic use
  • Humans
  • Hydroxybutyrates
  • Immunologic Factors / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Interferon-beta / therapeutic use
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting* / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting* / drug therapy
  • Nitriles / therapeutic use
  • Switzerland
  • Toluidines / therapeutic use
  • Treatment Outcome

Substances

  • Crotonates
  • Nitriles
  • Toluidines
  • Hydroxybutyrates
  • teriflunomide
  • Dimethyl Fumarate
  • Glatiramer Acetate
  • Interferon-beta
  • Immunologic Factors
  • Immunosuppressive Agents