Recurrence of disease activity after fingolimod discontinuation in older patients previously stable on treatment

Pantazou, Vasiliki; Pot, Caroline; Pasquier, Renaud Du; Goff, Géraldine Le; Théaudin, Marie

doi:10.1016/j.msard.2021.102918

Cited by 16 publications

(18 citation statements)

References 24 publications

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“…Although 0/57 patients in our shortinterval group experienced a relapse within 6 months, in a recent review of 128 patients discontinuing fingolimod followed for up to 6 months, overall 12.5% (16/128) experienced a relapse. 14 There have been 2 mechanisms suggested for the fingolimod discontinuation rebound activity. The first mechanism has to do with dramatic postdiscontinuation increase in circulating peripheral lymphocyte counts.…”

Section: Discussionmentioning

confidence: 99%

“…Although 0/57 patients in our short-interval group experienced a relapse within 6 months, in a recent review of 128 patients discontinuing fingolimod followed for up to 6 months, overall 12.5% (16/128) experienced a relapse. 14 …”

Section: Discussionmentioning

confidence: 99%

“…13 Clinical approaches to minimize this rebound have been variable and variably effective. 8 , 14 Unfortunately, clinical trials provide limited guidance because recent use of S1P modulators was exclusionary for both ocrelizumab 15 and ofatumumab 16 phase 3 trials (<2% participants with prior exposure). Therefore, real-world data sets are necessary.…”

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confidence: 99%

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Transitioning From S1P Receptor Modulators to B Cell–Depleting Therapies in Multiple Sclerosis

Rowles

Hsu

McPolin

et al. 2022

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesPatients with multiple sclerosis (MS) transition from oral sphingosine-1-receptor (S1P) modulators to anti-CD20 therapies for several circumstances. Optimal timing of this transition is uncertain, given competing concerns of rebound disease activity and ensuring immune reconstitution. The objective of this study was to evaluate the relationship between inflammatory activity and the transition period from fingolimod to anti-CD20 therapies in a real-world MS cohort.MethodsMedical records were reviewed for all patients at our center transitioning from fingolimod to rituximab or ocrelizumab between 2010 and October 2020. Time periods reviewed were the following: before fingolimod discontinuation, interval between fingolimod and anti-CD20 treatments, and after the first anti-CD20 infusion. The primary outcome was clinical relapses; MRI activity, time to absolute lymphocyte count (ALC) recovery, and infections were secondary. Clinical and demographic factors significant in univariable analyses were included in multivariable analyses.ResultsTransition data were available for 108 patients (68.5% women, 68.5% relapsing-remitting MS, mean age 44.6 years). The median (interquartile range) interval between fingolimod and anti-CD20 therapy was 28 (1–115.2) days. Six of 51 patients (11.8%) with intervals >1 month and 0/57 patients with shorter intervals experienced a relapse (MRI confirmed) within 6 months of fingolimod discontinuation. In the year following anti-CD20 initiation, 4/108 patients (3.7%) experienced a relapse (median 214.5 days after infusion). An additional 7% of those undergoing contrast-enhanced MRIs developed Gd+ lesions. ALC normalized following treatment switch in 89/92; the interval between treatments was unrelated to ALC recovery or infection.DiscussionDelaying anti-CD20 start to monitor ALC after S1P modulator discontinuation may not be necessary and could increase rebound risk. ALC monitoring could instead occur after a rapid switch to anti-CD20 treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Transitioning From S1P Receptor Modulators to B Cell–Depleting Therapies in Multiple Sclerosis

Rowles

Hsu

McPolin

et al. 2022

Neurol Neuroimmunol Neuroinflamm

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“…The possibility of the disease severely worsening after discontinuation ("rebound activity") of fingolimod should be considered, particularly with a disease onset at a younger age, in initially highly active disease, previous treatment with natalizumab, and occurrence of lymphopenia < 0.3 G/L in the first 3 months of treatment [79][80][81]. The exact mechanism of this "rebound activity" is unclear to date; therefore, it is currently unclear whether this is a class effect of all S1PRMs.…”

Section: Commentarymentioning

confidence: 99%

Specific Aspects of Immunotherapy for Multiple Sclerosis in Switzerland—A Structured Commentary, Update 2022

Friedli

Salmen

Hoepner

et al. 2022

CTN

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Multiple sclerosis (MS), particularly relapsing MS (RMS), has become a treatable disease in recent decades, and immunotherapies are now able to influence long-term disease course. A wide range of disease-modifying drugs are available, which makes the choice of therapy in individual cases considerably more complex. Due to specific regulatory aspects (partly diverging approvals by Swissmedic compared to the European Medicines Agency (EMA), and an independent evaluation process for the Federal Office of Public Health (FOPH) specialities list (SL)), we issued a consensus recommendation regarding specific aspects of immunotherapy for MS in Switzerland in 2019. Here, we present revised recommendations with an update on newly approved drugs and new safety aspects, also in reference to the risk of COVID-19 infection and vaccination.

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“…10 However, such an approach must be carefully evaluated to balance the temptation to stop or delay specific DMTs to reduce the risk of severe COVID-19 outcomes and the potential impact on MS reactivation and disability progression that such a treatment choice could imply. 11,12 Choice of treatment strategy, in general and particularly during the COVID-19 pandemic, should take into account differences in MoA and duration of the immunologic effects of each therapy, which can vary and may be short-lasting or persist for some years. 13 The cumulative effect of DMT sequencing on the immune system must also be carefully evaluated.…”

mentioning

confidence: 99%

Risk of Getting COVID-19 in People With Multiple Sclerosis

Iaffaldano

Lucisano

Manni

et al. 2022

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesSeveral studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR).MethodsA case-control (1:2) study was set up. Cases included PwMS with a confirmed diagnosis of COVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score–matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administered DMT, previous DMT sequences, or the place where the last treatment was administered.ResultsA total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02) with a higher risk of contracting COVID-19. Patients receiving natalizumab as last DMT (OR [95% CI]: 2.38 [1.66–3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16–2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34–2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home.DiscussionThis case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS.Classification of EvidenceThis study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective.

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Recurrence of disease activity after fingolimod discontinuation in older patients previously stable on treatment

Cited by 16 publications

References 24 publications

Transitioning From S1P Receptor Modulators to B Cell–Depleting Therapies in Multiple Sclerosis

Transitioning From S1P Receptor Modulators to B Cell–Depleting Therapies in Multiple Sclerosis

Specific Aspects of Immunotherapy for Multiple Sclerosis in Switzerland—A Structured Commentary, Update 2022

Risk of Getting COVID-19 in People With Multiple Sclerosis

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