1901. Safety, Tolerability and Efficacy of Fluoxetine as an Antiviral for Enterovirus D68 Associated Acute Flaccid Myelitis: A Retrospective Multicenter Cohort Study
Session: Poster Abstract Session: Antiviral Therapies
Saturday, October 6, 2018
Room: S Poster Hall

Background: Most patients with enterovirus (EV) D68-associated acute flaccid myelitis (AFM) have long-term disability. No effective therapies have been identified. Fluoxetine is the only FDA-approved medication with in vitro antiviral activity against EV-D68. This study retrospectively analyzed the safety, tolerability, and efficacy of fluoxetine for EV-D68-associated AFM.

Methods: A multicenter cohort study of US children with AFM in 2015-2016 compared serious adverse events (SAEs), adverse effects, and outcomes between fluoxetine-treated patients and untreated controls with AFM. Fluoxetine was administered at the discretion of treating providers with data gathered retrospectively. The primary outcome was summative limb strength score (SLSS; sum of Medical Research Council strength in all four limbs).

Results: 56 patients with AFM from 12 centers met study criteria (Figure 1). Among 30 patients exposed to fluoxetine, no SAEs were reported and adverse effects were similar to controls (p=0.16). The 28 patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified (57.1% vs 14.3%, p=0.001). Fluoxetine-treated patients had similar strength on initial exam compared to untreated controls (mean SLSS 12.9 vs. 14.3, p=0.313), but more severe paralysis at nadir (mean SLSS 9.25 vs. 12.82, p=0.023) and latest follow-up (mean SLSS 12.5 vs. 16.4, p=0.005) (Figure 2). In propensity-adjusted analysis, SLSS from initial exam to latest follow-up decreased by 0.2 (95%CI: -1.8 to +1.4) in fluoxetine-treated patients and increased by 2.5 (95%CI: +0.7 to +4.4) in controls (p=0.015).

Conclusion: Fluoxetine was safely administered and relatively well-tolerated. Patients with AFM treated with fluoxetine were more likely to have EV-D68-associated disease and had more severe paralysis at nadir and poorer long-term outcomes. These data do not suggest a positive efficacy signal for fluoxetine as a potential antiviral therapy for AFM.

 

Kevin Messacar, MD1, Stefan Sillau, PhD2, Sarah Hopkins, MD3, Catherine Otten, MD4, Molly Wilson-Murphy, MD5, Brian Wong, MD6, Jonathan Santoro, MD7, Andrew Treister, MD8, Harlori Tokhie, MD9, Alcy Torres, MD10, Luke Zabrocki, MD11, Julia Glanternik, MD12, Amanda L. Hurst, PharmD13, Jan Martin, MD2, Teri Schreiner, MD14, Naila Makhani, MD15, Roberta DeBiasi, MD, MS, FIDSA, FPIDS16, Michael Kruer, MD9, Adriana H. Tremoulet, MD, MAS17, Keith Van Haren, MD7, Jay Desai, MD18, Leslie Benson, MD5, Mark Gorman, MD5, Mark Abzug, MD19, Kenneth Tyler, MD20 and Samuel Dominguez, MD, PhD21, (1)Pediatric Infectious Diseases and Hospital Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, (2)University of Colorado, Aurora, CO, (3)Children's Hospital of Philadelphia, Philadelphia, PA, (4)Seattle Children's Hospital, Seattle, WA, (5)Boston Children's Hospital, Boston, MA, (6)Children's Hospital of Los Angeles, Los Angeles, CA, (7)Stanford University, Palo Alto, CA, (8)University of California San Diego, San Diego, CA, (9)Phoenix Children's Hospital, Phoenix, AZ, (10)Boston Medical Center, Boston, MA, (11)Naval Medical Center of San Diego, San Diego, CA, (12)Yale University, New Haven, CT, (13)Pharmacy, Children's Hospital Colorado, Aurora, CO, (14)Neurology, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, (15)Yale, New Haven, CT, (16)Pedatrics (Infectious Diseases, Microbiology, Immunology and Tropical Medicine, Childrens National Health System/GWU School of Medicine, Washington, DC, (17)University of California, San Diego, La Jolla, CA, (18)Division of Neurology, Children's Hospital Los Angeles, Los Angeles, CA, (19)University of Colorado School of Medicine, Children's Hospital, Aurora, CO, (20)University of Colorado Health Sciences Center, Aurora, CO, (21)Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO

Disclosures:

K. Messacar, None

S. Sillau, None

S. Hopkins, None

C. Otten, None

M. Wilson-Murphy, None

B. Wong, None

J. Santoro, None

A. Treister, None

H. Tokhie, None

A. Torres, None

L. Zabrocki, None

J. Glanternik, None

A. L. Hurst, None

J. Martin, None

T. Schreiner, None

N. Makhani, None

R. DeBiasi, None

M. Kruer, None

A. H. Tremoulet, None

K. Van Haren, None

J. Desai, None

L. Benson, None

M. Gorman, None

M. Abzug, None

K. Tyler, None

S. Dominguez, None

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