Association of Very Early Treatment Initiation With the Risk of Long-term Disability in Patients With a First Demyelinating Event

Abstract

IntroductionEarly treatment is associated with better long-term outcomes in patients with a first demyelinating event and early multiple sclerosis (MS). However, magnetic resonance (MR) findings are not usually integrated to construct propensity scores (PS) when evaluating outcomes. We assessed the association of receiving very early treatment with the risk of long-term disability including an MR Score (MRS) in patients with a first demyelinating event.MethodsWe included 580 patients with a first demyelinating event prospectively collected between 1994 and 2021, who received at least one disease modifying drug (DMD). Patients were classified into tertiles according to the cohort’s distribution of the time from the first demyelinating event to the first DMD: First tertile (FT) or very early treatment (6 months; N=194); second (ST) (6.1-16 months, N=192), and third tertile (TT) (16.1 months, N=194). A 5-point MRS was built according to the sum of the following indicators: ≥9 brain lesions (1pt); ≥1 infratentorial lesion (1pt); ≥1 spinal cord (SC) lesion (1pt); ≥1 contrast-enhancing (CE) brain lesion (1pt); ≥1 CE SC lesion (1pt). PS based on covariates and the MRS was computed for each of the outcomes. Inverse PS-weighted Cox and linear regression models assessed the risk of different outcomes between tertile groups. Finally, to confirm the role of MR in treatment decision, we studied the time elapsed from the first demyelinating event to treatment initiation according to the MRS in all patients with radiological available information, re-named as raw-MRS.ResultsVery early treatment decreased the risk of reaching EDSS 3.0 (HR 0.55 [95% CI 0.32; 0.97]), secondary progressive MS (HR 0.40 [95% CI 0.19; 0.85]), sustained disease progression at 12 months after treatment initiation (HR 0.50 [95% CI 0.29; 0.84]), when compared to patients from the TT group. Patients from the FT had a lower disability progression rate (β estimate, -0.009 [95% CI -0.016; -0.002]) and a lower severe disability measured by the PDDS (β estimate, -0.52 [95% CI -0.91; -0.13]) than the TT groups. Finally, there was a 62.4% reduction in the median time between the first demyelinating event and the first-ever treatment initiation from patients displaying a raw-MRS 1 to patients with a raw-MRS 5.ConclusionUsing PS models with and without MRS, we showed that treatment initiation at very early stages is associated with a reduction in the risk of long-term disability accrual in patients with a first demyelinating event.Classification of Evidence:This study provides Class III evidence that earlier treatment of MS patients presenting with a first demyelinating event is associated with improved clinical outcomes.

Diagnostic delay of multiple sclerosis: prevalence, determinants and consequences

“…Short delays in DMT initiation may increase the risk of long-term disability. 33 Our study suggests even relatively short DDs are associated with unfavourable consequences on disease activity. Although a greater relapse frequency was not observed in patients with a longer DD, these patients tended to have numerous risk factors associated with unfavourable disease outcomes, including a greater EDSS scores, lesion numbers on brain MRI and NfL levels, at MS diagnosis.…”

Vaccine Safety and Immunogenicity in Patients With Multiple Sclerosis Treated With Natalizumab

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Assignment Completed

“…In a recent study published in Neurology , investigators showed that very early treatment, within 6 months of onset of a first demyelinating event, was associated with lower rates of disability progression. 7 Similarly, in a large registry of patients with optic neuritis, early administration of immunomodulatory therapy was associated with less visual and disability progression. 8…”

“…In a recent study published in Neurology, investigators showed that very early treatment, within 6 months of onset of a first demyelinating event, was associated with lower rates of disability progression. 7 Similarly, in a large registry of patients with optic neuritis, early administration of immunomodulatory therapy was associated with less visual and disability progression. 8 New methods to detect optic nerve dysfunction have emerged and were used in the study by Vidal-Jordana et al 5 Intereye differences in OCT by 5 μm for retinal nerve fiber layer and 4 μm for the ganglion cell and inner plexiform layer were previously shown to be important thresholds for establishing an optic nerve lesion.…”