Induction treatment strategy in multiple sclerosis: a review of past experiences and future perspectives

Ruggieri, Serena; Pontecorvo, Simona; Tortorella, Carla; Gasperini, Claudio

doi:10.1186/s40893-018-0037-7

Cited by 22 publications

(20 citation statements)

References 47 publications

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“…However, early clinical and radiological features have limited prognostic value and optimizing the treatment selection, based on the patient's expected clinical outcome, remains a significant challenge. 24 Our results demonstrate that the characterization of CSF inflammatory profile allows to better predict the disease severity. The model including CSF parameters more accurately identified patients at risk of disease activity than the model including only clinical and MRI variables.…”

Section: Discussionmentioning

confidence: 58%

The CSF Profile Linked to Cortical Damage Predicts Multiple Sclerosis Activity

Magliozzi

Scalfari

Pisani

et al. 2020

Annals of Neurology

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Objective Intrathecal inflammation correlates with the grey matter damage since the early stages of multiple sclerosis (MS), but whether the cerebrospinal fluid (CSF) profile can help to identify patients at risk of disease activity is still unclear. Methods We evaluated the association between CSF levels of 18 cytokines, previously found to be associated to grey matter damage, and the disease activity, among 99 patients with relapsing‐remitting MS, who underwent blinded clinical and 3 T magnetic resonance imaging (MRI) evaluations for 4 years. Groups with evidence of disease activity (EDA) or no evidence of disease activity (NEDA; occurrence of relapses, new white matter lesions, and Expanded Disability Status Scale [EDSS] change) were identified. Cortical lesions and the annualized cortical thinning were also evaluated. Results Forty‐one patients experienced EDA and, compared to the NEDA group, had at diagnosis higher CSF levels of CXCL13, CXCL12, IFNγ, TNF, sCD163, LIGHT, and APRIL (p < 0.001). In the multivariate analysis, CXCL13 (hazard ratio [HR] = 1.35; p = 0.0002), LIGHT (HR = 1.22; p = 0.005) and APRIL (HR = 1.78; p = 0.0001) were the CSF molecules more strongly associated with the risk of EDA. The model, including CSF variables, predicted more accurately the occurrence of disease activity than the model with only clinical/MRI parameters (C‐index at 4 years = 71% vs 44%). Finally, higher CSF levels of CXCL13 (β = 4.7*10−4; p < 0.001), TNF (β = 3.1*10−3; p = 0.004), LIGHT (β = 2.6*10−4; p = 0.003), sCD163 (β = 4.3*10−3; p = 0.009), and TWEAK (β = 3.4*10−3; p = 0.024) were associated with more severe cortical thinning. Interpretation A specific CSF profile, mainly characterized by elevated levels of B‐cell related cytokines, distinguishes patients at high risk of disease activity and severe cortical damage. The CSF analysis may allow stratifications of patients at diagnosis for optimizing therapeutic approaches. ANN NEUROL 2020;88:562–573

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Section: Discussionmentioning

confidence: 58%

The CSF Profile Linked to Cortical Damage Predicts Multiple Sclerosis Activity

Magliozzi

Scalfari

Pisani

et al. 2020

Annals of Neurology

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“…One common therapeutic approach is to use a first-line DMT that is considered safe and moderately efficacious (relative to higher-efficacy DMTs), followed by a period of monitoring and escalation to more efficacious treatment as disease activity necessitates [ 173 ]. Conversely, treating early with high-efficacy therapies may prevent the accumulation of irreversible long-term CNS damage [ 174 ]. However, high-efficacy therapies may be associated with greater risk of SAEs [ 175 ].…”

Section: The Role Of Im Ifn β-1a In the Current Ms Therapeutic Landscapementioning

confidence: 99%

Interferons and Multiple Sclerosis: Lessons from 25 Years of Clinical and Real-World Experience with Intramuscular Interferon Beta-1a (Avonex)

et al. 2021

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Recombinant interferon (IFN) β-1b was approved by the US Food and Drug Administration as the first disease-modifying therapy (DMT) for multiple sclerosis (MS) in 1993. Since that time, clinical trials and real-world observational studies have demonstrated the effectiveness of IFN therapies. The pivotal intramuscular IFN β-1a phase III trial published in 1996 was the first to demonstrate that a DMT could reduce accumulation of sustained disability in MS. Patient adherence to treatment is higher with intramuscular IFN β-1a, given once weekly, than with subcutaneous formulations requiring multiple injections per week. Moreover, subcutaneous IFN β-1a is associated with an increased incidence of injection-site reactions and neutralizing antibodies compared with intramuscular administration. In recent years, revisions to MS diagnostic criteria have improved clinicians’ ability to identify patients with MS and have promoted the use of magnetic resonance imaging (MRI) for diagnosis and disease monitoring. MRI studies show that treatment with IFN β-1a, relative to placebo, reduces T2 and gadolinium-enhancing lesions and gray matter atrophy. Since the approval of intramuscular IFN β-1a, a number of high-efficacy therapies have been approved for MS, though the benefit of these high-efficacy therapies should be balanced against the increased risk of serious adverse events associated with their long-term use. For some subpopulations of patients, including pregnant women, the safety profile of IFN β formulations may provide a particular benefit. In addition, the antiviral properties of IFNs may indicate potential therapeutic opportunities for IFN β in reducing the risk of viral infections such as COVID-19.

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“…Taka strategia pozwala na szybsze i trwalsze osiągnięcie remisji, ale do jej wad należy narażenie pacjentów na działania niepożądane immunosupresantów [16]. Istotą tego modelu jest możliwie krótkie stosowanie silnej immunosupresji, jednak wystarczające do uzyskania zadowalającej kontroli nad aktywnością choroby, a następnie zmiana leczenia polegająca na wprowadzenia słabszych immunomodulatorów w celu utrzymania efektów leczenia [21]. Lekami stosowanymi w początkowej fazie są m.in.…”

Section: Diagnostyka Smunclassified