Relapse Rate and MRI Activity in Young Adult Patients With Multiple Sclerosis: A Post Hoc Analysis of Phase 3 Fingolimod Trials

Abstract

BackgroundDisease activity differs in young patients with multiple sclerosis (MS) compared with the overall adult MS population.ObjectiveThe objective of this paper is to evaluate the effect of fingolimod 0.5 mg on disease activity in young adults with MS from three randomized, double-blind Phase 3 trials.MethodsAnnualized relapse rate (ARR), number of new/newly enlarging T2 lesions (neT2), and no evidence of disease activity (NEDA-3) were estimated in the intent-to-treat population at age 20 (youngest) and 30 (young) and compared to the overall population. Models used included a negative binomial regression (ARR/neT2) and a logistic regression (NEDA), with age at baseline as a continuous covariate.ResultsARRs were higher in younger patients (all p < 0.05), and significantly reduced with fingolimod versus placebo or interferon beta-1a (IFN β-1a), with the percentage reduction inversely proportional to age. Fingolimod was significantly associated with a lower number of neT2 lesions versus placebo/IFN in all age groups except versus IFN in the youngest patients. Regardless of age, fingolimod-treated patients were more likely to achieve NEDA-3 versus placebo/IFN β-1a, with strongest benefits in the youngest patients (all p < 0.05).ConclusionsYoung adults show higher levels of MS disease activity, and may particularly benefit from fingolimod treatment compared with the overall study population.

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

“…We studied IL37 levels in patients with PP-, SP-, and RR-MS in stable disease or during relapses. It has been generally accepted that inflammatory processes within the CNS in MS are more exaggerated in the younger population [57], and therefore our findings that higher IL37 levels were associated with younger age (p = 0.047) are in line with this notion. Additionally, we demonstrated that higher IL37 levels were associated with lower MSSS (p = 0.039), thus supporting the previously mentioned hypothesis that IL37 produced in response to ongoing immunoinflammatory events in MS might downregulate the progression of the disease.…”

Effect of fingolimod on MRI outcomes in patients with paediatric-onset multiple sclerosis: results from the phase 3 PARADIGMSstudy

“…MRI disease activity in the paediatric population was generally higher at baseline (mean age: 15.3 years; T2 lesion volume 10 207 mm 3 ; Gd+ T1 lesions 2.9) than the disease activity observed in a comparable adult population recruited for an actively controlled clinical trial (mean age: 36 years; T2 lesion volume 4924 mm 3 ; Gd+ T1 lesions 1.06) 29. The high baseline disease activity observed in the present study is consistent with previous observations of higher activity in young adult patients30 compared with adult-onset MS. For example, the disease activity as measured by the annualised rate of formation of new/enlarging T2 lesions and number of Gd+ T1 lesions per scan after at least 3 months were 4.39 and 0.44, respectively, with fingolimod treatment and 9.27 and 1.28, respectively, with IFN β-1a in the present study. The T2 lesion rate in our study was 2.6-fold greater with fingolimod and 3.5-folder greater with IFN β-1a than observed in adult patients with MS in the 12-month TRANSFORMS study (fingolimod: 1.7 and IFN β-1a: 2.6) 29.…”

Possible regenerative effects of fingolimod (FTY720) in multiple sclerosis disease: An overview on remyelination process

“…In both acute and chronic demyelination stages, FTY720 showed an increase in gray/white matter contrast, which is a marker of myelination (Ziser et al, 2018). In a clinical study on young MS patients, FTY720 prevented a new generation of enlarging T2 lesion (Gärtner et al, 2018). Active lesions appear hypointense in T1-weighted images.…”

“…OPCs, and oligodendrocytes. The effect of FTY720 is highly TA B L E 3 Summary of the effect of FTY720 on myelination in clinical trials (Gärtner et al, 2018) 6 and 12 months post-FTY720 treatment RRMS • T1and T2 enhancing lesions remained stable, no significant changes when comparing pre-to post-FTY720 treatment (Sternberg et al, 2018) Two years FTY720 administration RRMS • CGMF stability • Preservative effect on CNS tissue (Yousuf et al, 2017) Administration in INFORM trial study, 3-5 years oral FTY720 administration, 1.25 and 0.5 mg doses (Gaetano et al, 2018) 12 month FTY720 treatment RRMS • Promotion of axonal integrity • Reduction in white matter demyelination (Gurevich et al, 2018) dependent on the time of administration and dosage. Finding the optimum time and dose of FTY720 could be a golden key for increasing remyelination in MS patients.…”