Risk of COVID-19 infection and severe disease in MS patients on different disease-modifying therapies

Smith, Tyler; Madhavan, Maya; Gratch, Daniel; Patel, Aneek; Saha, Valerie; Sammarco, Carrie; Rimler, Zoe; Zuniga, Guadalupe; Gragui, Dunia; Charvet, Leigh; Cutter, Gary; Krupp, Lauren; Kister, Ilya; Ryerson, Lana Zhovtis

doi:10.1016/j.msard.2022.103735

Cited by 26 publications

(32 citation statements)

References 53 publications

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“…Treatment with S1PR modulators itself does not seem to increase the risk for severe COVID-19 disease ( 27 – 29 ). However, the lacking immune response to active SARS-CoV-2 vaccination caused by the S1PR modulator treatment does constitute a risk factor, and most of our patients who were treated with SARS-CoV-2-neutralizing antibodies had additional risk factors for severe COVID-19 beyond the lacking vaccination response.…”

Section: Discussionmentioning

confidence: 99%

Case report: Variant-specific pre-exposure prophylaxis of SARS-CoV-2 infection in multiple sclerosis patients lacking vaccination responses

et al. 2022

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Sphingosine-1-phosphate receptor modulators and anti-CD20 treatment are widely used disease-modifying treatments for multiple sclerosis. Unfortunately, they may impair the patient’s ability to mount sufficient humoral and T-cellular responses to vaccination, which is of special relevance in the context of the SARS-CoV-2 pandemic. We present here a case series of six multiple sclerosis patients on treatment with sphingosine-1-phosphate receptor modulators who failed to develop SARS-CoV-2-specific antibodies and T-cells after three doses of vaccination. Due to their ongoing immunotherapy, lacking vaccination response, and additional risk factors, we offered them pre-exposure prophylactic treatment with monoclonal SARS-CoV-2-neutralizing antibodies. Initially, treatment was conducted with the antibody cocktail casirivimab/imdevimab. When the SARS-CoV-2 Omicron variant became predominant, we switched treatment to monoclonal antibody sotrovimab due to its sustained neutralizing ability also against the Omicron strain. Since sotrovimab was approved only for the treatment of COVID-19 infection and not for pre-exposure prophylaxis, we switched treatment to tixagevimab/cilgavimab as soon as it was granted marketing authorization in the European Union. This antibody cocktail has retained, albeit reduced, neutralizing activity against the Omicron variant and is approved for pre-exposure prophylaxis. No severe adverse events were recorded for our patients. One patient had a positive RT-PCR for SARS-CoV-2 under treatment with sotrovimab, but was asymptomatic. The other five patients did not develop symptoms of an upper respiratory tract infection or evidence of a SARS-CoV-2 infection during the time of treatment up until the finalization of this report. SARS-CoV-2-neutralizing antibody treatment should be considered individually for multiple sclerosis patients lacking adequate vaccination responses on account of their immunomodulatory treatment, especially in times of high incidences of SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

Case report: Variant-specific pre-exposure prophylaxis of SARS-CoV-2 infection in multiple sclerosis patients lacking vaccination responses

et al. 2022

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“…( Holmberg and Andersen, 2022 Apr 5 , Longinetti et al, 2022 Aug 22 , Petri and Urquhart, 1991 Apr , Simpson-Yap et al, 2022 Aug 29 , Smith et al, 2022 Mar 11 , Sormani et al, 2021 , Yu and Zhou, 2015 Jun 9 , Griffith et al, 2020 Nov 12 , Casey et al, 2022 )…”

Section: Uncited Referencesmentioning

confidence: 99%

Electronic health record data for assessing risk of hospitalization for COVID-19: Methodological considerations applied to multiple sclerosis

Dillon¹,

Siadimas²,

Roumpanis³

et al. 2023

Multiple Sclerosis and Related Disorders

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“…Smith et al 66 examined 1439 patients with MS on DMDs, of whom 230 had COVID‐19. They reported that, whereas no mAbs (NTZ, OCR, and RTX) were found to be significantly associated with an increased risk for the onset of infection, RTX was associated with increased severity 66 . Salter et al 64 also reported that RTX, but not OCR, was associated with hospitalization.…”

Section: Viral Infectionsmentioning

confidence: 99%

“…In a large cohort of patients with MS and COVID‐19 from 28 countries, Simpson‐Yap et al 63 reported that RTX was associated with a higher risk of hospitalization, ICU admission, and the need for artificial ventilation, while OCR was associated with hospitalization and ICU admission. Smith et al 66 examined 1439 patients with MS on DMDs, of whom 230 had COVID‐19. They reported that, whereas no mAbs (NTZ, OCR, and RTX) were found to be significantly associated with an increased risk for the onset of infection, RTX was associated with increased severity 66 .…”

Section: Viral Infectionsmentioning

confidence: 99%

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Infectious issues of therapeutic monoclonal antibodies in multiple sclerosis and neuromyelitis optica spectrum disorders

Tagawa

2022

Clinical & Exp Neuroim

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Various effective monoclonal antibodies (mAbs) have been approved for both multiple sclerosis (MS) and anti-aquaporin-4-seropositive neuromyelitis optica spectrum disorders worldwide, including in Japan. As these newer mAbs have distinct modes of action that effectively suppress the recurrence of inflammation and slow disability progression, they can modulate and interfere with the protective immune response against pathogens, resulting in various infectious complications. Among various mAbs, natalizumab (NTZ) has the highest risk of causing progressive multifocal leukoencephalopathy (PML), a rare but fatal opportunistic brain infection caused by John Cunningham polyomavirus. Switching from NTZ to B-cell-depleting mAbs, such as ocrelizumab, is also a possible risk factor for PML development. Alemtuzumab carries the risk of reactivation of varicella-zoster virus (VZV); therefore, prophylactic acyclovir treatment is required. NTZ has also been associated with VZV reactivation.Eculizumab can cause severe meningococcal infection due to Neisseria meningitis, and vaccination prior to treatment induction is required. Attention to the reactivation of hepatitis B or Mycobacterium tuberculosis is also needed during mAb therapy. Additionally, in the era of severe acute respiratory syndrome coronavirus 2 infection (COVID-19), the risk for of developing severe COVID-19 may be associated with some mAbs, such as B-cell-depleting agents. Thorough understanding and mitigation strategies for infectious risks are essential.

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Risk of COVID-19 infection and severe disease in MS patients on different disease-modifying therapies

Cited by 26 publications

References 53 publications

Case report: Variant-specific pre-exposure prophylaxis of SARS-CoV-2 infection in multiple sclerosis patients lacking vaccination responses

Case report: Variant-specific pre-exposure prophylaxis of SARS-CoV-2 infection in multiple sclerosis patients lacking vaccination responses

Electronic health record data for assessing risk of hospitalization for COVID-19: Methodological considerations applied to multiple sclerosis

Infectious issues of therapeutic monoclonal antibodies in multiple sclerosis and neuromyelitis optica spectrum disorders

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