Initial lymphocyte count and low BMI may affect fingolimod-induced lymphopenia

Warnke, Clemens; Dehmel, Thomas; Ramanujam, Ryan; Holmén, Carolina; Nordin, Nina; Wolfram, Kathleen; Leussink, Verena I.; Hartung, Hans‐Peter; Olsson, Tomas; Kieseier, Bernd C.

doi:10.1212/wnl.0000000000001049

Cited by 26 publications

(31 citation statements)

References 6 publications

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“…Therefore, a marker is needed that can predict an excessive decrease of lymphocytes after fingolimod treatment. Previously, patients with a low lymphocyte number before fingolimod treatment and underweight women were prone to lymphopenia after fingolimod treatment 11 . In addition, underweight women are at risk for low lymphocytes 10 , yet the incidence rate of females with MS is higher than males 12 .…”

Section: Discussionmentioning

confidence: 99%

Fingolimod-induced decrease in heart rate may predict subsequent decreasing degree of lymphocytes

Ikeda

Kakuma

Watari

et al. 2018

Sci Rep

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Here, we determined whether degree of decreased heart rate due to fingolimod treatment correlates with decreasing degree of lymphocytes in relapse-remitting multiple sclerosis (RRMS). In total, 30 patients with RRMS were treated with 0.5 mg fingolimod and their heart rate recorded every 30 minutes for 24 hours. Time trends of heart rate were characterised as three individual amplitudes and phase angles from three cosine curves using a mixed-effect model. Spearman’s correlation coefficient and regression analysis were used to determine the effect of heart rate information on change in lymphocyte count pre- and post-fingolimod treatment. Moreover, the degree of decreased lymphocytes induced by fingolimod treatment on heart rate was compared between low and high influence groups. Positive correlation between amplitude from the second curve and difference in lymphocyte number (p = 0.006) was observed. Regression analysis was also significant (p = 0.002). Moreover, the second curve derived from the high amplitude group exhibited a greater decrease in lymphocyte number after fingolimod treatment than the low amplitude group (p < 0.001). We suggest that the degree of decreased lymphocytes after fingolimod treatment (main effect) may be predicted by estimating the influence of degree in heart rate (side effect).

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Section: Discussionmentioning

confidence: 99%

Fingolimod-induced decrease in heart rate may predict subsequent decreasing degree of lymphocytes

Ikeda

Kakuma

Watari

et al. 2018

Sci Rep

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“…Although the rate of infections seems to be unrelated to lymphocyte counts and was not significantly elevated with fingolimod in randomized and observational trials, 55 , 57 monitoring and rapid treatment of infections is advisable. Two cases of fatal hemophagocytic syndrome have occurred, both associated with infections.…”

Section: How Should Fingolimod Therapy Be Monitored?mentioning

confidence: 97%

“…52 Patients with low initial lymphocyte counts and women with low body mass index (<18.5 mg/m 2 ) are at higher risk of developing lymphopenia. 55 Liver enzymes >5-fold above the upper limit of normal at two different lab examinations should lead to withdrawal of fingolimod. 16 In addition, yet described in a preliminary study, the dosage of fingolimod may be reduced from 0.5 mg per day to 0.5 mg every second or third day in patients with elevated liver enzymes or reduced lymphocyte counts.…”

Section: How Should Fingolimod Therapy Be Monitored?mentioning

confidence: 99%

Fingolimod for multiple sclerosis and emerging indications: appropriate patient selection, safety precautions, and special considerations

Ayzenberg¹,

Hoepner²,

Kleiter³

2016

TCRM

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Fingolimod (FTY720), an immunotherapeutic drug targeting the sphingosine-1-phosphate receptor, is a widely used medication for relapsing-remitting multiple sclerosis (MS). Apart from the pivotal Phase III trials demonstrating efficacy against placebo and interferon-β-1a once weekly, sufficient clinical data are now available to assess its real-world efficacy and safety profile. Approved indications of fingolimod differ between countries. This discrepancy, to some extent, reflects the intermediate position of fingolimod in the expanding lineup of MS medications. With individualization of therapy, appropriate patient selection gets more important. We discuss various scenarios for fingolimod use in relapsing-remitting MS and their pitfalls: as first-line therapy, as escalation therapy after failure of previous immunotherapies, and as de-escalation therapy following highly potent immunotherapies. Potential side effects such as bradycardia, infections, macular edema, teratogenicity, and progressive multifocal leukoencephalopathy as well as appropriate safety precautions are outlined. Disease reactivation has been described upon fingolimod cessation; therefore, patients should be closely monitored for MS activity for several months after stopping fingolimod. Finally, we discuss preclinical and clinical data indicating neuroprotective effects of fingolimod, which might open the way to future indications such as stroke, Alzheimer’s disease, and other neurodegenerative disorders.

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“…Four cases of PML during treatment of MS with dimethylfumarate have been reported so far (Table 2). Treatment with fingolimod can also be associated with susceptibility to infection (8). A direct connection between the extent of lymphopenia-and, in occasional cases, granulocytopenia-and an increased risk of infection under fingolimod treatment has not been demonstrated (8).…”

Section: Immunotherapymentioning

confidence: 99%

“…Treatment with fingolimod can also be associated with susceptibility to infection (8). A direct connection between the extent of lymphopenia-and, in occasional cases, granulocytopenia-and an increased risk of infection under fingolimod treatment has not been demonstrated (8). To date, nine cases of PML have been reported in patients being given fingolimod alone who had not been treated with natalizumab immediately beforehand (Table 2) (9).…”

Section: Immunotherapymentioning

confidence: 99%

Interdisciplinary Risk Management in the Treatment of Multiple Sclerosis

Havla¹,

Warnke²,

Kappos³

et al. 2016

Deutsches Ärzteblatt International

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Initial lymphocyte count and low BMI may affect fingolimod-induced lymphopenia

Abstract: Our findings suggest that patients with low baseline lymphocyte counts and underweight women in which fingolimod treatment will be initiated should possibly be monitored more closely.

Cited by 26 publications

References 6 publications

Fingolimod-induced decrease in heart rate may predict subsequent decreasing degree of lymphocytes

Fingolimod-induced decrease in heart rate may predict subsequent decreasing degree of lymphocytes

Fingolimod for multiple sclerosis and emerging indications: appropriate patient selection, safety precautions, and special considerations

Interdisciplinary Risk Management in the Treatment of Multiple Sclerosis

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