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

Barry, B.P.; Erwin, April; Stevens, J. C.; Tornatore, Carlo

doi:10.1007/s40120-019-00160-9

Cited by 106 publications

(100 citation statements)

References 58 publications

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“…4 Therapeutic decision-making is more challenging in patients with active COVID-19 in whom discontinuation of immunotherapies could lead to rebound disease activity (e.g., fingolimod). 5,6 In our patient, despite multiple comorbidities, the COVID-19 was resolved with good outcome, and there was no need for intensive care unit or intubation. Of note is that the initial presentation of COVID-19 was worsening of neurologic symptoms, which is commonly seen in patients with MS in context of infections.…”

Section: Discussionmentioning

confidence: 58%

COVID-19 infection in a patient with multiple sclerosis treated with fingolimod

Barzegar

Mirmosayyeb

Nehzat

et al. 2020

Neurol Neuroimmunol Neuroinflamm

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In December 2019, a novel coronavirus causing an infectious respiratory disease was identified, which since then has developed into a pandemic with higher rates of mortality in older individuals and those with underlying medical conditions. 1 Multiple sclerosis (MS) is an immune-mediated neurologic disease which requires long-term treatment with immunotherapies that have been shown to increase the risk of infections. 2 As a result, there is significant anxiety among patients and neurologists during the pandemic regarding the infection outcome in this patient population. We present a patient with MS treated with fingolimod who was diagnosed with COVID-19 and had a favorable outcome. Case presentationA 42-year-old woman who was diagnosed with relapsing-remitting MS according to the McDonald criteria in 2001 and had been treated with methotrexate (2 years; discontinued because of elevated liver enzymes), interferon beta 1-a (13 years; discontinued because of disease activity), and recently on fingolimod (since 4 years ago) presented with muscle aches, gait difficulty, sensory disturbances, and weakness on the right side. Her other comorbidities included major depression disorder, hypothyroidism, recurrent urinary tract infection, and histories of pulmonary embolism on direct oral anticoagulation and myasthenia gravis (diagnosed 5 years before MS and status after thymectomy). At her most recent follow-up in September 2019, her expanded disability status scale (EDSS) score was 1.0 for a positive Babinski sign on the right side. MRI was notable for moderate disease burden in the brain and the presence of 2 right-sided cervical cord lesions. Her lymphocyte count at this visit was 842.4/μL.On March 1, 2020, she started experiencing the symptoms that gradually worsened over the next few days. She sought medical attention on March 5 and was seen at the outpatient MS clinic. Neurologic examination revealed decreased sensation, reduced muscle strength (4/5), and brisk reflexes on the right and right positive Babinski sign (EDSS of 4). These findings were consistent with new relapse or recrudescence of old symptoms (pseudoexacerbation). She was then admitted for a relapse workup and treatment on the same day. On arrival, she was afebrile with vital signs within normal limits. Initial laboratory investigations were notable for C-reactive protein of 76 mg/L and erythrocyte sedimentation rate of 46 mm, raising suspicious for an underlying infectious etiology. There was also a decrease in absolute lymphocyte count (601.6/μL), which was attributed to fingolimod. Methylprednisolone IV 1,000 mg/d was initiated for 3 days for the treatment of a possible relapse. As part of the infectious workup, chest X-ray showed a ground glass opacity ( figure, A), which raised a possibility of community-acquired pneumonia for which she was started on azithromycin 500 mg daily because she is allergic to fluoroquinolones. On March 7, she developed dry cough, dyspnea, and fever (38.7°C). She also had tachycardia (122), increased respiratory rate (30...

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Section: Discussionmentioning

confidence: 58%

COVID-19 infection in a patient with multiple sclerosis treated with fingolimod

Barzegar

Mirmosayyeb

Nehzat

et al. 2020

Neurol Neuroimmunol Neuroinflamm

View full text Add to dashboard Cite

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“…In addition, notwithstanding the low circulating lymphocytes, in fingolimod immunosuppressed patients, T and B cells in the lymphonode may rapidly expand and mount an effective immune response that favors COVID-19 recovery after drug discontinuation ( Chiarini et al., 2020 ). Note that, after discontinuation of fingolimod, there is a risk of MS relapse due to a ‘rebound’ effect ( Barry et al., 2019 ), thus longer fingolimod treatment suspension should be avoided.…”

Section: Discussionmentioning

confidence: 99%

Asymptomatic SARS-CoV-2 infection in two patients with multiple sclerosis treated with fingolimod

Mallucci

Zito²,

Fabbro³

et al. 2020

Multiple Sclerosis and Related Disorders

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“…Treatment interruption may be considered if ALC goes below 200/mm 3 although the impact of this low level of circulating lymphocytes on infection risk is not well defined [ 58 ]. Stopping fingolimod has been linked to severe rebound MS activity, thus timely initiation of another potent DMT is recommended to avoid the need for hospitalization and the increased exposure risk [ 59 ]. In addition to the two cases mentioned above, six additional cases of COVID-19 infection in patients with MS taking fingolimod have been reported to the time of this writing [ 38 , 41 , 60 – 62 ].…”

Section: Current Multiple Sclerosis Disease-modifying Therapiesmentioning

confidence: 99%

Multiple Sclerosis Disease-Modifying Therapy and the COVID-19 Pandemic: Implications on the Risk of Infection and Future Vaccination

et al. 2020

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The coronavirus 2019 (COVID-19) pandemic is expected to linger. Decisions regarding initiation or continuation of diseasemodifying therapy for multiple sclerosis have to consider the potential relevance to the pandemic. Understanding the mechanism of action and the possible idiosyncratic effects of each therapeutic agent on the immune system is imperative during this special time. The infectious side-effect profile as well as the route and frequency of administration of each therapeutic agent should be carefully considered when selecting a new treatment or deciding on risk mitigation strategies for existing therapy. More importantly, the impact of each agent on the future severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) vaccine should be carefully considered in treatment decisions. Moreover, some multiple sclerosis therapies may have beneficial antiviral effects against SARS-CoV-2 while others may have beneficial immune-modulating effects against the cytokine storm and hyperinflammatory phase of the disease. Conventional injectables have a favorable immune profile without an increased exposure risk and therefore may be suitable for mild multiple sclerosis during the pandemic. However, moderate and highly active multiple sclerosis will continue to require treatment with oral or intravenous high-potency agents but a number of risk mitigation strategies may have to be implemented. Immune-modulating therapies such as the fumerates, sphinogosine-1P modulators, and natalizumab may be anecdotally preferred over cell-depleting immunosuppressants during the pandemic from the immune profile standpoint. Within the cell-depleting agents, selective (ocrelizumab) or preferential (cladribine) depletion of B cells may be relatively safer than non-selective depletion of lymphocytes and innate immune cells (alemtuzumab). Patients who develop severe iatrogenic or idiosyncratic lymphopenia should be advised to maintain social distancing even in areas where lockdown has been removed or ameliorated. Patients with iatrogenic hypogammaglobulinemia may require prophylactic intravenous immunoglobulin therapy in certain situations. When the future SARS-CoV-2 vaccine becomes available, patients with multiple sclerosis should be advised that certain therapies may interfere with mounting a protective immune response to the vaccine and that serological confirmation of a response may be required after vaccination. They should also be aware that most multiple sclerosis therapies are incompatible with live vaccines if a live SARS-CoV-2 vaccine is developed. In this article, we review and compare disease-modifying therapies in terms of their effect on the immune system, published infection rates, potential impact on SARS-CoV-2 susceptibility, and vaccine-related implications. We propose risk mitigation strategies and practical approaches to disease-modifying therapy during the COVID-19 pandemic.

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

Cited by 106 publications

References 58 publications

COVID-19 infection in a patient with multiple sclerosis treated with fingolimod

COVID-19 infection in a patient with multiple sclerosis treated with fingolimod

Asymptomatic SARS-CoV-2 infection in two patients with multiple sclerosis treated with fingolimod

Multiple Sclerosis Disease-Modifying Therapy and the COVID-19 Pandemic: Implications on the Risk of Infection and Future Vaccination

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