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Abstract
Background and Objectives Early 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 (PSs) 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.
Methods We included 580 patients with a first demyelinating event prospectively collected between 1994 and 2021, who received at least 1 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 tertile (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 (1 point); ≥1 infratentorial lesion (1 point); ≥1 spinal cord (SC) lesion (1 point); ≥1 contrast-enhancing (CE) brain lesion (1 point); and ≥1 CE SC lesion (1 point). 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 radiologic available information, renamed as raw-MRS.
Results Very early treatment decreased the risk of reaching Expanded Disability Status Scale 3.0 (hazard ratio [HR] 0.55, 95% CI 0.32–0.97), secondary progressive MS (HR 0.40, 95% CI 0.19–0.85), and sustained disease progression at 12 months after treatment initiation (HR 0.50, 95% CI 0.29–0.84), when compared with patients from the TT group. Patients from the FT group had a lower disability progression rate (β estimate −0.009, 95% CI −0.016 to −0.002) and a lower severe disability measured by the Patient-Determined Disease Step (β estimate −0.52, 95% CI −0.91 to −0.13) than the TT group. 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.
Discussion Using 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 patients with MS presenting with a first demyelinating event is associated with improved clinical outcomes.
Glossary
- AIC=
- Akaike information criterion;
- CEL=
- contrast-enhancing lesion;
- CST=
- contrast sensitivity test;
- CT=
- clinical trial;
- DMD=
- disease-modifying drug;
- EDSS=
- Expanded Disability Status Scale;
- FT=
- first tertile;
- HR=
- hazard ratio;
- IPW=
- inverse probability weighting;
- IQR=
- interquartile range;
- KM=
- Kaplan-Meier;
- MDT=
- manual dexterity test;
- MR=
- magnetic resonance;
- MRS=
- MR score;
- MS=
- multiple sclerosis;
- MSPT=
- multiple sclerosis performance test;
- OCB=
- oligoclonal band;
- OR=
- odds ratio;
- PDDS=
- Patient-Determined Disease Step;
- PROM=
- patient-reported outcome measure;
- PS=
- propensity score;
- PST=
- processing speed test;
- QoL=
- quality of life;
- SDP=
- sustained disability progression;
- SPMS=
- secondary progressive MS;
- ST=
- second tertile;
- TT=
- third tertile;
- WST=
- walking speed test
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editors were Deputy Editor Bradford Worrall, MD, MSc, FAAN and Assistant Editor Amy Kunchok, MBBS, MMed, FRACP.
Editorial, page 549
CME Course: NPub.org/cmelist
Class of Evidence: NPub.org/coe
- Received July 19, 2022.
- Accepted in final form June 2, 2023.
- © 2023 American Academy of Neurology
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