Alemtuzumab as rescue therapy in a cohort of 50 relapsing–remitting MS patients with breakthrough disease on fingolimod: a multi-center observational study

Huhn, Konstantin; Bayas, Antonios; Doerck, Sebastian; Frank, Benedikt; Gerbershagen, Kathrin; Hellwig, Kerstin; Kallmann, Boris; Kleinschnitz, Christoph; Kleiter, Ingo; Lee, Dong Hoon; Limmroth, Volker; Mäurer, Mathias; Meuth, Sven G.; Rieckmann, Peter; Ruck, Tobias; Gold, Ralf; Linker, Ralf A.

doi:10.1007/s00415-018-8871-2

Cited by 34 publications

(30 citation statements)

References 26 publications

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“…A case of severe disease reactivation 19 days after infusion of rituximab 1 g after a 6-week fingolimod washout has been reported, suggesting that a 6-week washout period may be too long in some patients [53]. In one cohort, 9/36 patients with highly active MS who switched from fingolimod to alemtuzumab had significant disease activity during the first year of alemtuzumab treatment [54], but larger cohorts have found alemtuzumab to be an effective option after fingolimod [55,56].…”

Section: Choice Of Next Therapymentioning

confidence: 99%

Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations

et al. 2019

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Because the treatment of multiple sclerosis (MS) may span decades, the need often arises to make changes to the treatment plan in order to accommodate changing circumstances. Switching drugs, or the discontinuation of immunomodulatory agents altogether, may leave patients vulnerable to relapse or disease progression. In some cases, severe MS disease activity is noted clinically and on MRI after treatment withdrawal. When this disease activity is disproportionate to the pattern observed prior to treatment initiation, patients are said to have experienced rebound. Of the US Food and Drug Administration (FDA)-approved agents to treat MS, the drugs most commonly implicated in rebound are natalizumab and fingolimod. In this review based on the reported cases and data from clinical trials, we characterize disease rebound after fingolimod cessation. We also outline fingolimod rebound management considerations, summarizing what evidence is available to help clinicians mitigate the risk of rebound, switch therapies, and treat rebound events when they occur. The commonly encountered situation of fingolimod discontinuation prior to pregnancy is also discussed.

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Section: Choice Of Next Therapymentioning

confidence: 99%

Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations

et al. 2019

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“…A retrospective analysis of 50 patients transitioning from fingolimod to alemtuzumab showed a strong reduction in disease activity within 12 months after the switch. 26 However, in another series of patients treated sequentially with fingolimod and then alemtuzumab, nine were identified as experiencing disease activity within 12 months after alemtuzumab Course 1. 27 Even though animal studies showed some degree of lymphocyte depletion in lymph nodes after alemtuzumab administration, 8 the authors speculated that residual sequestration in lymph nodes after cessation of fingolimod treatment could protect lymphocytes from alemtuzumab-mediated depletion and contribute to persistence of disease activity.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of alemtuzumab over 6 years in relapsing–remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies

Wijmeersch

Boster

et al. 2019

Mult Scler

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Background: Alemtuzumab is administered as two annual courses for relapsing–remitting multiple sclerosis (MS). Patients may relapse before completing the two-course regimen. Objective: The objective was to evaluate 6-year outcomes in patients who relapsed between alemtuzumab Courses 1 and 2 (early relapsers). Methods: Post hoc analysis of patients from the Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) studies who enrolled in the extension. Results: Early relapsers (CARE-MS I: 15%; CARE-MS II: 24%) had more relapses in 1–2 years pre-alemtuzumab and higher mean baseline Expanded Disability Status Scale score than patients without relapse. Their annualized relapse rate declined from Year 1 (CARE-MS I: 1.3; CARE-MS II: 1.2) to Year 2 following Course 2 (0.3; 0.5) and remained low thereafter. Over 6 years, 60% remained free of 6-month confirmed disability worsening; 24% (CARE-MS I) and 34% (CARE-MS II) achieved 6-month confirmed disability improvement. During Year 6, 69% (CARE-MS I) and 68% (CARE-MS II) were free of magnetic resonance imaging (MRI) disease activity. Median percent yearly brain volume loss (Year 1: −0.67% (CARE-MS I); −0.47% (CARE-MS II)) declined after Course 2 (Year 6: −0.24%; −0.13%). Conclusion: Early relapsers’ outcomes improved after completing the second alemtuzumab course. These findings support administering the approved two-course regimen to maximize clinical benefit. ClinicalTrials.gov registration numbers: CARE-MS I, II, extension: NCT00530348, NCT00548405, NCT00930553.

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“…There have been case reports of clinical worsening after switching from fingolimod to ocrelizumab, rituximab, or alemtuzumab. [150][151][152] Conversely, there are reports that rituximab and alemtuzumab are effective in patients with an inadequate response to fingolimod, 153,154 although persistent T cell depletion may occur after a fingolimod-alemtuzumab switch. 155 A washout period has traditionally been recommended when switching among second-line agents to allow lymphocyte counts and other indices (e.g., liver enzymes) to return to normal.…”

Section: Treatment Sequencingmentioning

confidence: 99%

Treatment Optimization in Multiple Sclerosis: Canadian MS Working Group Recommendations

Freedman

Devonshire

Duquette

et al. 2020

Can. J. Neurol. Sci.

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Abstract:The Canadian Multiple Sclerosis Working Group has updated its treatment optimization recommendations (TORs) on the optimal use of disease-modifying therapies for patients with all forms of multiple sclerosis (MS). Recommendations provide guidance on initiating effective treatment early in the course of disease, monitoring response to therapy, and modifying or switching therapies to optimize disease control. The current TORs also address the treatment of pediatric MS, progressive MS and the identification and treatment of aggressive forms of the disease. Newer therapies offer improved efficacy, but also have potential safety concerns that must be adequately balanced, notably when treatment sequencing is considered. There are added discussions regarding the management of pregnancy, the future potential of biomarkers and consideration as to when it may be prudent to stop therapy. These TORs are meant to be used and interpreted by all neurologists with a special interest in the management of MS.

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Alemtuzumab as rescue therapy in a cohort of 50 relapsing–remitting MS patients with breakthrough disease on fingolimod: a multi-center observational study

Cited by 34 publications

References 26 publications

Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations

Fingolimod Rebound: A Review of the Clinical Experience and Management Considerations

Efficacy of alemtuzumab over 6 years in relapsing–remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies

Treatment Optimization in Multiple Sclerosis: Canadian MS Working Group Recommendations

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