What to expect after natalizumab cessation in a real-life setting

Salhofer‐Polanyi, Sabine; Baumgärtner, Alexander; Kraus, J.; Maida, E.; Schmied, M.; Leutmezer, Fritz

doi:10.1111/ane.12250

Cited by 35 publications

(48 citation statements)

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“…At 24 weeks after natalizumab cessation, there was a significant reduction in the annualized relapse rate between the pre-natalizumab period and the post-natalizumab period (2 vs 0.3; p = 0.009), 128 and a reduction in the mean number of relapses (1.1 vs 0.07), although no p values were reported, 120 according to fair quality evidence. At 52 weeks after natalizumab discontinuation, several studies of fair to poor quality reported a statistically significant reduction in the annualized relapse rate compared with that during the pre-natalizumab period 131,135,137,138 or described a reduction without statistical calculations. 123,126 However, other studies of fair quality reported no change in the annualized relapse rate and mean number of relapses between the two time periods.…”

Section: Review Questionmentioning

confidence: 99%

“…Across 11 studies, 2 reported no evidence of rebound 123,135 and 1 reported no evidence of immune reconstitution inflammatory syndrome. 128 The proportion of participants showing evidence of rebound ranged, in most of the studies, from 9% to 12%, 126,127,131,132,137 whereas other authors reported higher rebounds, including 14%, 136 21.2% 134 and 38.3%. 138 Relapse outcomes.…”

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confidence: 93%

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ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

et al. 2018

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Background and scopeMultiple sclerosis (MS) is an inflammatory-demyelinating disease of the central nervous system (CNS) that is characterized by inflammation, demyelination and degenerative changes. MS usually begins around the age between 20 and 40 years and affects two to three times as many women as men; it also constitutes the most frequent cause of non-traumatic disability in the young adult population. 1 The incidence of MS varies across regions, with rates as high as 8 to 10 new cases per 100,000 in high latitudinal regions. 2,3 Current estimates suggest that over 700,000 people are affected in Europe, with over 2.5 million cases worldwide, 4 which represent a significant burden in terms of impact on quality of life, societal costs and personal expenses. 5,6 Most patients (85%-90%) have a relapsing course from onset that is characterized by relapses and remissions of neurological symptoms Methods: This guideline has been developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and following the updated EAN recommendations. Clinical questions were formulated in Patients-Intervention-Comparator-Outcome (PICO) format and outcomes were prioritized. The quality of evidence was rated into four categories according to the risk of bias. The recommendations with assigned strength (strong and weak) were formulated based on the quality of evidence and the risk-benefit balance. Consensus between the panelists was reached by use of the modified nominal group technique. Results: A total of 10 questions were agreed, encompassing treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and treatment strategies in MS and pregnancy. The guideline takes into account all disease-modifying drugs approved by the European Medicine Agency (EMA) at the time of publication. A total of 21 recommendations were agreed by the guideline working group after three rounds of consensus. Conclusion:The present guideline will enable homogeneity of treatment decisions across Europe. associated with areas of CNS inflammation, and over the course of two decades, more than half of untreated patients transition to a phase of gradual worsening independent of acute attacks. 7,8 Progressive forms of MS can be present as the initial disease course (primary-progressive MS) in approximately 10%-15% of patients. 9,10 There is no curative treatment available for MS, and the current therapeutic strategy is aimed at reducing the risk of relapses and potentially disability progression. The treatment era for MS began in 1993, when the first interferon became available, and recent years have seen a large expansion in the therapeutic options for MS, with 11 disease-modifying therapies (DMTs) approved by the European Medicine Agency (EMA) in both injectable and oral formulations by the beginning of 2017. 11 The growing armamentarium of therapies brings new opportunities for individualized therapy where patients and providers must balance considerations around efficacy,...

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Section: Review Questionmentioning

confidence: 99%

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ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

et al. 2018

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“…In a Danish cohort, 83/375 (22.1%) of patients presented a rebound after stopping the treatment (Sorensen et al., ). Another analysis of 200 patients who discontinued NTZ, 11.9% present a rebound activity (Salhofer‐Polanyi et al., ). Recently, an analysis of 47 NTZ withdrawals found a significant clinical worsening (defined as a two‐step EDSS increase) in 19% of patients (Vidal‐Jordana et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…The rebound rate varies among studies between 10% and 30% of patients (Gueguen et al, 2014;Havla et al, 2011;Kerbrat et al, 2011;Miravalle et al, 2011;Rinaldi et al, 2012;Salhofer-Polanyi et al, 2014;Sorensen et al, 2014;Vidal-Jordana et al, 2015). The reactivation of the disease activity occurs frequently within the 3-6 months after NTZ cessation, in relation with the drug pharmacodynamics features (Kerbrat et al, 2011;O'Connor et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Frequently, after NTZ cessation the activity of the disease returns to pretreatment levels (Fox et al, 2014;O'Connor et al, 2011); however, some cases with severe clinical and radiological worsening have been described (Beume et al, 2015;Daelman et al, 2012;Gueguen et al, 2014;Jander et al, 2012;Kerbrat et al, 2011;Lenhard et al, 2010;Miravalle et al, 2011;Papeix et al, 2011;Rigau et al, 2012;Rinaldi et al, 2012;Salhofer-Polanyi et al, 2014;Sorensen et al, 2014;Vellinga et al, 2008;West & Cree, 2010) probably related to immune reconstitution inflammatory syndrome (IRIS; Lenhard et al, 2010;Miravalle et al, 2011).…”

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Catastrophic outcome of patients with a rebound after Natalizumab treatment discontinuation

et al. 2017

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IntroductionNatalizumab (NTZ) is an effective drug for the treatment of relapsing‐remitting multiple sclerosis. In some patients discontinuation is mandatory due to the risk of progressive multifocal leukoencephalopathy. However, severe clinical and radiological worsening has been described after drug cessation. Our aim was to describe the clinical and radiological features of the rebound phenomenon.Material and MethodsPatients switched from NTZ to Fingolimod (FTY) who had presented a rebound after discontinuation were selected. Clinical and magnetic resonance imaging (MRI) data were collected.ResultsFour JC virus positive patients were included. The mean disease duration was 9.5 years (SD: 4.12) with a mean time of 3.1 years on NTZ. All patients started FTY within 3–4 months. Neurological deterioration started in a mean time of 3.5 months (SD: 2.08) with multifocal involvement: 75% motor disturbances, 50% cognitive impairment, 25% seizures. The average worsening in Expanded Disability Status Scale [EDSS] was of 3.25 points (SD: 2.33). The MRI showed a very large increase in T2 and gadolinium‐enhanced lesions (mean: 23.67, SD: 18.58). All patients received 5 days of IV methylprednisolone, one patient required plasma exchange. All the patients presented neurological deterioration with an EDSS worsening of 1.13 points (SD: 0.48). After the rebound three patients continued treatment with FTY, only one patient restarted NTZ.ConclusionDiscontinuation of NTZ treatment may trigger a severe rebound with marked clinical and radiological worsening. A very careful evaluation of benefit‐risk should be considered before NTZ withdrawal, and a close monitoring and a short washout period is recommended after drug withdrawal.

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Multiple Sclerosis Disease Activity and Disability Following Discontinuation of Natalizumab for Pregnancy

et al. 2022

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Key Points Question Is early natalizumab cessation before or during the first trimester of pregnancy associated with multiple sclerosis relapse occurrence and relapse-related disability? Findings In this cohort study of 274 pregnancies, relapses during pregnancy and postpartum were common, with more than 10% of women retaining clinically meaningful disability from pregnancy-related natalizumab cessation relapses 1 year after delivery. Neither pregnancy itself, restarting natalizumab shortly after delivery, nor exclusive breastfeeding was associated with protection against these relapses. Meaning These findings suggest that women with multiple sclerosis need to be informed about the risks of early natalizumab cessation due to pregnancy or planned pregnancy, and treatment alternatives should be considered.

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What to expect after natalizumab cessation in a real-life setting

Abstract: Our data suggest that rebound of MS disease activity affects a subgroup of patients (11.9%), especially those with low disease activity before natalizumab therapy and a longer treatment gap after its withdrawal.

Cited by 35 publications

References 20 publications

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

Catastrophic outcome of patients with a rebound after Natalizumab treatment discontinuation

Multiple Sclerosis Disease Activity and Disability Following Discontinuation of Natalizumab for Pregnancy

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