De-Escalation from High- or Moderate-Efficacy to Low-Efficacy Disease Modifying Therapy in Patients with Multiple Sclerosis Shown to be Safe According to New Research

According to a recent presentation at the 2023 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC), de-escalating from a high- or moderate-efficacy disease modifying therapy (DMT) to a low-efficacy DMT for treating MS is associated with similar safety and quality of life outcomes as remaining on the higher-efficacy DMT. Outcomes examined by researchers included annualized relapse rates (ARR), MRI activity, disability levels, and patient-reported outcomes. Although previous studies have investigated the effects of DMT discontinuation on other outcomes, including safety, this study addresses a comparative lack of research regarding DMT de-escalation. 

Using Cleveland Clinic electronic medical records, the retrospective cohort study identified 135 patients with MS who switched from a high- or moderate-efficacy DMT (DMT 1) to a low-efficacy DMT (DMT 2), most commonly due to safety concerns, tolerability, or adverse events. The most common DMT 1s were dimethyl fumarate (70.4%) and fingolimod (23.7%), while the most common DMT 2s were glatiramer acetate (42.2%) and interferons (21.5%). Researchers used mixed-effects models and non-inferiority (NI) tests to evaluate the outcomes of interests, with an NI margin of no more than 8% for disease activity after de-escalation. Disease activity for DMT 2 vs DMT 1 was compared via odds ratio (OR) or rate ratio (RR), estimated by covariate-adjusted logistic or Poisson regression.

According to the study results, the ARR, disability level, and MRI activity after de-escalation from DMT 1 to DMT 2 were NI. The RR for ARR and OR for disability level were statistically insignificant and below NI thresholds, and higher ARRs measured before the first DMT persisted throughout the study period.

There is currently a lack of universal guidelines for optimal DMT sequencing during MS treatment. Therefore, research like the current study that investigates the safety of different sequencing approaches is critical. The study authors from the Cleveland Clinic, Northshore University Health System, and Touro University College of Osteopathic Medicine note that care providers must consider each patient’s disease characteristics when making treatment decisions.