Disability progression in multiple sclerosis patients using early first‐line treatments

Abstract

Background and purpose: Therapeutic management of relapsing-remitting multiple sclerosis (RRMS) has evolved towards early treatment. The objective was to assess the impact of early treatment initiation on disability progression amongst RRMS first-line-treated patients. Methods: This study included all incident RRMS cases starting interferon or glatiramer acetate for the first time from 1 January 1996 to 31 December 2012 (N = 5279) from 10 MS expert Observatoire Français de la Sclérose en Plaques centres. The delay from treatment start to attaining an irreversible Expanded Disability Status Scale (EDSS) score of 3.0 was compared between the early group (N = 1882; treated within 12 months following MS clinical onset) and the later group using propensity score weighted Kaplan-Meier methods, overall and stratified by age.Results: Overall, the restricted mean time before reaching EDSS 3.0 from treatment start was 11 years and 2 months for patients treated within the year following MS clinical onset and 10 years and 7 months for patients treated later. Thus, early treated patients gained 7 months (95% confidence interval [CI] 4-11 months) in the time to reach EDSS 3.0 compared to patients treated later (treatment start delayed by 28 months). The difference in restricted mean time was respectively 6 months (95% CI 1-10 months) and 14 months (95% CI 4-24 months) in the ≤40 years age group and in the >40 years age group, in favour of the early group. Conclusions:Early treatment initiation resulted in a significant reduction of disability progression amongst patients with RRMS, and also amongst older patients.

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

“…Second, time to treatment initiation is accounted for at the time of disease onset instead of at MS diagnosis. 12,[18][19][20]22,24 This is important because in this study, the included classical MS covariates are collected when the clinical disease starts and not in a time frame in which the disease might evolve or progress. 40,41 Other important difference is that in our cohort, patients are allowed to enter on risk of disability before the MS diagnosis, as long as treatment is initiated between the first demyelinating event and MS diagnosis.…”

“…12,[18][19][20][21][22][23] Despite the effectiveness displayed by real-world studies on decreasing risk of disability, it is important to underline some methodological shortcomings influencing results. 12,[18][19][20][21][22][23][24] In multicentric studies, data are usually collected following different protocols, which makes such information difficult to harmonize under a common database. For instance, differences in inclusion criteria, clinical visit frequency, scales to measure disability, or the use of predetermined variables among centers may add inconsistency when gathering information within the same platform.…”

“…It is also worth pointing out that real-world studies evaluating the effect of time to treatment initiation on disability include prospective information both from MS diagnosis (with information about the first demyelinating event recorded retrospectively) and from the first event in a proportion of patients. 19,21,24-27 Nonetheless, studies assessing this outcome and focusing exclusively in a prospective deeply phenotyped cohort (prospective standardized collection of demographic, clinical, and radiologic information and blood samples) followed up from the first demyelinating event are needed.…”

Long-Term Disability Outcomes in Relapsing–Remitting Multiple Sclerosis Patients: Impact of Clinical and Demographic Factors on Disease Progression

“…We selected an EDSS score of 3.0 as the initial disability milestone because it signifies the beginning of mild to moderate irreversible disability. Additionally, an EDSS score of 6.0 was chosen as the subsequent milestone because it marks the first sign of dependence on ambulatory assistance [ 36 , 37 ].…”

Long-term clinical outcomes in patients with multiple sclerosis who are initiating disease-modifying therapy with natalizumab compared with BRACETD first-line therapies

“… 1 , 2 The initiation of treatment with a disease-modifying therapy (DMT) at the time of first presentation of symptoms consistent with or suggestive of MS provides benefits over delaying treatment. 3 – 8 Long-term follow-up of patients from randomized trials has shown a greater benefit for patients originally assigned to treatment groups as opposed to those originally assigned to placebo groups. 9 – 14 …”