Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis

Lizak, Nathaniel; Lugaresi, Alessandra; Alroughani, Raed; Lechner‐Scott, Jeannette; Slee, Mark; Havrdová, Eva; Horáková, Dana; Trojano, María; Izquierdo, Guillermo; Duquette, Pierre; Girard, Marc; Prat, Alexandre; Grammond, Pierre; Hupperts, Raymond; Grand’Maison, François; Sola, Patrizia; Pucci, Eugenio; Bergamaschi, Roberto; Oreja‐Guevara, Celia; Pesch, Vincent Van; Ramo, Cristina; Spitaleri, Daniele; Iuliano, Gerardo; Boz, Cavit; Granella, Franco; Olascoaga, Javier; Verheul, Freek; Rózsa, Csilla; Cristiano, Edgardo; Flechter, Shlomo; Hodgkinson, Suzanne; Amato, Maria Pia; Deri, Norma; Jokubaitis, Vilija; Spelman, Tim; Butzkueven, Helmut; Kalinčík, Tomáš

doi:10.1136/jnnp-2016-313976

Cited by 53 publications

(43 citation statements)

References 29 publications

(38 reference statements)

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“…Recent studies suggest that patients experiencing relapses at EDSS ≥3.5 are less likely to recover vs those with relapses at lower EDSS levels . We can surmise that although relapses become less frequent in each 5 year epoch after onset, the severity of these events in our most vulnerable patients (later MS) points to an important treatment opportunity with our DMTs (lauded primarily for their ability to decrease the frequency and severity of early relapses).…”

Section: Discussionmentioning

confidence: 87%

“…Interpreting similar results with a background assumption of a likely independence between the processes of acute attacks and slow worsening, one study of similar design concluded “relapses play an independent and significant role for worsening of MS.” However, given the presence of relapse free progression occurring at the same rate as relapse‐associated progression, the investigators in one study chose a cautious stance interpreting their results, concluding that relapses were not definitively shown to contribute to long‐term disability . Yet another recent study found a positive correlation between relapses and worsening throughout the course of MS, and proposed that methodological issues concerning relapse rates had obscured this issue in prior studies …”

Section: Discussionmentioning

confidence: 99%

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Multiple sclerosis relapses contribute to long‐term disability

et al. 2019

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The degree to which relapses with incomplete recovery (RW) contribute to the overall picture of worsening disability in relapse-onset multiple sclerosis (RMS) remains unclear. 1,2 Clarification of this issue may determine the extent to which elimination of relapses through immunotherapy can result in long-term benefits. Incomplete recovery from relapses implies a contribution of these circumscribed events to the irreversible process of tissue destruction. 3,4 Better understanding of the impact of relapses vs slow progression may also help us understand the complex relationship between inflammation vs degeneration, which evolves over a lifetime of RMS. Some epidemiologists opine that the majority of disability accumulated in MS over time results from a more or less degenerative process involving slow progression, whereas relapses contribute little to the long-term picture. 5 This view is challenged in more recent studies. 6,7 We sought to calculate the frequency of RW in the first 15 years of longitudinally followed RMS patients, using a clinical definition of incomplete recovery from relapse, and to compare the frequency of year-to-year slow progressive worsening (PW). Furthermore, we Background: Treatments affect both relapse-related disability and short-term disability change, but measurements of their impact on long-term outcomes remain a challenge.Objective: To ascertain the contribution of relapse-associated disability to overall disability in relapse-onset multiple sclerosis (RMS) using long-term data collected in our clinic. Materials and Methods: Retrospective study of a cohort of newly diagnosed patients with RMS, (n = 176) was undertaken, measuring all confirmed changes in disability up to 15 years after onset. Worsening was assessed yearly and in 5-year epochs and was attributed to either relapse (RW) or slow progression (PW). Results: At data lock, 139/176 (81%) of patients were still actively followed, with Expanded Disability Status Scale (EDSS) available for 10 years post-onset in 145/176 (82%) patients and 15 years post-onset EDSS in 83 patients (mean follow-up entire group 12.7 years post-onset). RW accounted for a large amount of worsening seen in the first 15 years of RMS. RW was less frequent over time, but accounted for most EDSS changes in the first decade of MS (167/267, 63% of EDSS changes), and remained important even in years 11-15 (17/50, 34% of EDSS changes). Median change in disability due to RW vs PW was similar over the entire 15 years.Conclusions: Worsening of treated MS was associated with relapses in many RMS patients throughout the first 15 years after onset, suggesting an opportunity for long-term benefit through relapse reduction. K E Y W O R D S expanded disability status scale, MS, progression, relapse | 337 SCOTT eT al.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Multiple sclerosis relapses contribute to long‐term disability

et al. 2019

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“…Some of these limitations may be overcome by using much larger data sets collected through multicenter collaborations. 21 Such studies can address more detailed questions concerning long-term treatment responses to multiple different medications but are thus far rare. Even single-center longitudinal studies such as ours, performed in the treatment era, remain rare and may reveal important changes in the real-world experience of MS care.…”

Section: Discussionmentioning

confidence: 99%

Outcomes in a Modern Cohort of Treated Patients with Multiple Sclerosis from Diagnosis Up to 15 Years

Scott¹,

Desai²,

Hackett³

et al. 2019

International Journal of MS Care

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Background: Before disease-modifying therapies (DMTs) were available, the natural history of multiple sclerosis (MS) regarding attainment of accepted disability milestones was reported with fairly wide variance comparing outcomes across studies. The influence of DMTs on these outcomes is unknown. This study aimed to calculate attainment of disability milestones during the first 15 years after onset of DMTtreated relapsing forms of MS (RMS). Methods: As a retrospective study, all available disability data (collected routinely) on all newly diagnosed patients with RMS seen and initially diagnosed ina single clinic between 1989 and 2006 were reviewed. Times from first symptoms and diagnosis until first treatment with DMTs were also reviewed. Time-toevent statistics were applied using disability milestones. Results: Mean follow-up of 184 adult patients from symptom onset was 13.7 years. Of patients followed up for 15 years after onset, 16 of 86 (19%) reached an Expanded Disability Status Scale (EDSS) score of 6.0. Estimated median time to reach an EDSS score of 3.0 was 10.7 years and to reach an EDSS score of 4.0 was 18.1 years.Conclusions: There were striking differences between the present results and older data sets and similar results to the few available modern data sets. This analysis of a modern treated RMS cohort provides outcomes data that may be compared favorably with the natural history of RMS. Int J MS Care. 2020;22:110-114.

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“…Blue lines indicate the rates of transition between EDSS steps 0, 3 and 6, stratified into quintiles (both before and after EDSS 3). Marked variability in disability progression rates is apparent before and after EDSS 3 (based on the data presented in Lizak et al10 ). 15.…”

mentioning

confidence: 99%

Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis

Cited by 53 publications

References 29 publications

Multiple sclerosis relapses contribute to long‐term disability

Multiple sclerosis relapses contribute to long‐term disability

Outcomes in a Modern Cohort of Treated Patients with Multiple Sclerosis from Diagnosis Up to 15 Years

Where there is inflammation, treatment may reduce disability progression – Yes

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