Evaluation of frequency, severity, and independent risk factors for recurrence of disease activity after fingolimod discontinuation in a large real-world cohort of patients with multiple sclerosis

Cerdá-Fuertes, Nuria; Nagy, Sara; Schaedelin, Sabine; Sinnecker, Tim; Ruberte, Esther; Papadopoulou, Athina; Wuerfel, Jens; Kühle, Jens; Yaldizli, Özgür; Kappos, Ludwig; Derfuss, Tobias; Décard, Bernhard F.

doi:10.1177/17562864221150312

Cited by 7 publications

(2 citation statements)

References 20 publications

(54 reference statements)

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“…Both S1P-RM and NTZ are treatments associated with recurring disease activity after withdrawal. 29 , 30 However, the rate of S1P-RM resuming MS activity was surprisingly high, affecting 80% of our patients with PML, compared with approximately 30% after withdrawal of fingolimod in the general population with MS. 29 , 31 Nevertheless, the percentage of patients experiencing recurring activity was comparable with those who discontinued S1P-RM without transitioning to another DMT. 29 In our cohort, the median delay of 4 months before recurring activity was in line with previous studies analyzing patients without PML.…”

Section: Discussionmentioning

confidence: 86%

Presentation and Outcome in S1P-RM and Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

Blant,

De Rossi,

Gold

et al. 2024

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesProgressive multifocal leukoencephalopathy (PML) is a severe neurologic disease resulting from JC virus reactivation in immunocompromised patients. Certain multiple sclerosis (MS) diseasemodifying therapies (DMTs) are associated with PML risk, such as natalizumab and, more rarely, sphingosine-1-phosphate receptor modulators (S1P-RMs). Although natalizumab-associated PML is well documented, information on S1P-RM-associated PML is limited. The aim of this study is to compare clinical presentations and outcomes between the 2 groups. MethodsA retrospective multicenter cohort study included patients with PML from 2009 to 2022 treated with S1P-RMs or natalizumab. Data on clinical and radiologic presentation, outcomes, immune reconstitution inflammatory syndrome (IRIS), survival, disability (using the modified Ranking scale-mRS), and MS relapses post-PML were analyzed. ResultsOf 88 patients, 84 were analyzed (20 S1P-RM, 64 natalizumab). S1P-RM-associated PML was diagnosed in older patients (median age 52 vs 44 years, p < 0.001) and after longer treatment duration (median 63.9 vs 40 months, p < 0.001). Similarly, S1P-RM patients were more prone to show symptoms at diagnosis (100 vs 80.6%, p = 0.035), had more disseminated lesions (80% vs 34.9%, p = 0.002), and had higher gadolinium enhancement (65% vs 39.1%, p = 0.042). Natalizumab patients had a higher IRIS development rate ). Overall, the outcome (mRS) at 12 months was similar in the 2 groups (OR: 0.81 [0.32-2.0]). Yet, posttreatment MS activity was higher in S1P-RM cases ).

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Section: Discussionmentioning

confidence: 86%

Presentation and Outcome in S1P-RM and Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

Blant,

De Rossi,

Gold

et al. 2024

Neurol Neuroimmunol Neuroinflamm

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“…To our knowledge, we are the first study investigating the age–sex interaction, but other studies have found younger age to be a risk factor as well. 20 , 22 , 34 , 37 In females with a pregnancy wish, exploring other treatment avenues to avoid potential cases with discontinuation followed by severe disease activation in the vulnerable period during or after pregnancy should be considered.…”

Section: Discussionmentioning

confidence: 99%

Risk of T2 lesions when discontinuing fingolimod: a nationwide predictive and comparative study

Wandall-Holm,

Holm,

Heick

et al. 2023

Brain Communications

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Fingolimod is a frequently used disease-modifying therapy in relapsing-remitting Multiple Sclerosis. However, case reports and small observational studies indicate a highly increased risk of disease reactivation after discontinuation. We aimed to investigate the risk of radiological disease reactivation in patients discontinuing fingolimod. We performed a nationwide cohort study in Denmark, including patients who discontinued fingolimod between January 2014 and January 2023. Eligibility was a diagnosis with relapsing-remitting Multiple Sclerosis, and two MRIs performed respectively within one year before and after discontinuing fingolimod. The included patients were compared to those discontinuing dimethyl fumarate with the same eligibility criteria in an unadjusted and matched propensity score analysis. Matching was done on age, sex, Expanded Disability Status Scale, MRI data, cause for treatment discontinuation, treatment duration, and relapse rate. The main outcome was the presence of new T2-lesions on the first MRI after treatment discontinuation. To identify high-risk patients among those discontinuing fingolimod, we made a predictive model assessing risk factors for obtaining new T2-lesions. Of 1.324 patients discontinuing fingolimod in the study period, 752 were eligible for inclusion (mean age [SD], years, 41 [10]; 552 females [73%]; median Expanded Disability Status Scale [Q1-Q3], 2.5 [2.0-3.5]; mean disease duration [SD], years, 12 [8]). Of 2.044 patients discontinuing dimethyl fumarate in the study period, 957 were eligible for inclusion, presenting similar baseline characteristics. Among patients discontinuing fingolimod, 127 [17%] had 1-2 new T2-lesions, and 124 [17%] had ≥3 new T2-lesions compared to 114 [12%] and 45 [5%], respectively for those discontinuing dimethyl fumarate, corresponding to odds ratios [95% CI] of 1.8 [1.3-2.3] and 4.4 [3.1-6.3]. The predictive model, including 509 of the 752 patients discontinuing fingolimod, showed a highly increased risk of new T2-lesions among those with disease activity during fingolimod treatment and among females under 40 years. This nationwide study suggests that discontinuing fingolimod in some cases carries a risk of developing new T2-lesions, emphasizing the importance of clinical awareness. If feasible, clinicians should prioritize the prompt initiation of new disease-modifying therapies, particularly among young females.

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Patient and Physician Perspectives of Treatment Burden in Multiple Sclerosis

Singer,

Morgan,

Stamm

et al. 2024

Neurol Ther

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The number of disease-modifying therapies (DMTs) approved for the treatment of multiple sclerosis (MS) has greatly increased in recent decades, leading to higher treatment complexity. DMTs can differ in mode and frequency of administration, benefit–risk profile, and associated costs. Patients with MS contend not only with the burden of their chronic disease but also with the treatment burden of their MS therapy. Adhering to dosing schedules and infusion appointments can be difficult for busy, working-age patients or those with limited access to transportation. Patients and healthcare professionals (HCPs) may have differing priorities, concerns, and preferences when selecting treatment, potentially affecting treatment satisfaction and, importantly, adherence. Additionally, patients face direct and indirect costs related to treatment. These factors can all contribute to a high treatment burden on patients, impacting their quality of life and potentially leading to worse patient outcomes. HCPs, patients, and caregivers must work together to alleviate treatment burden through effective communication, shared decision-making, appreciating each other’s perspectives, and additional HCP support. Consideration of treatment burden into clinical guidelines is also warranted. In this review, we examine key factors impacting treatment burden for patients with MS, with a focus on the patient perspective as provided by our patient authors, and provide strategies to minimize treatment burden.

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Evaluation of frequency, severity, and independent risk factors for recurrence of disease activity after fingolimod discontinuation in a large real-world cohort of patients with multiple sclerosis

Cited by 7 publications

References 20 publications

Presentation and Outcome in S1P-RM and Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

Presentation and Outcome in S1P-RM and Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

Risk of T2 lesions when discontinuing fingolimod: a nationwide predictive and comparative study

Patient and Physician Perspectives of Treatment Burden in Multiple Sclerosis

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