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Overview

• There are limited data on the use of various therapeutics to treat patients with WNV disease, such as standard and hyperimmune polyclonal immune globulin, monoclonal immune globulin, interferon, ribavirin, and corticosteroids.
• Most of the published data involve case reports and case series describing the use of different products in patients with WNV disease, with various dosing, timing of administration, and patient populations.
• Several products have been studied in controlled clinical trials, but the trials were often underpowered and the products showed no benefit.
• Larger, prospective, controlled clinical trials are needed to assess efficacy and the impact of factors such as dosing, timing, and patient populations who might benefit from certain treatments.
• Updated information about ongoing or completed clinical trials is available at .

Data on specific products

The following sections comprise brief summaries of published data describing use of various products for treatment of disease caused by WNV and some related flaviviruses. No pre-clinical studies are included in this review.

Polyclonal Intravenous Immune Globulin (IVIG)

In case reports and case series involving solid organ transplant (SOT) recipients with WNV neuroinvasive disease (including one report involving two patients with St. Louis encephalitis), the effects of IVIG treatment on survival and neurologic sequelae were variable. Reports differed in dosing and timing of IVIG administration (typically 400–500 mg/kg/day x 4–5 doses), concomitant treatment with other therapies (e.g., interferon alf-2b, WNV antibody-enriched fresh frozen plasma, ribavirin), and reduction of immunosuppression. Among 58 patients reported, 42 (72%) received IVIG, the majority had their immunosuppression reduced, and some received other therapies in addition to IVIG. Overall, 23% died and 43% of survivors were reported to have residual neurologic deficits, although follow-up and reporting was variable.12345678910

Interferon

In case reports and case series, patients with WNV neuroinvasive disease were treated with interferon alfa-2b alone or in combination with other therapies including IVIG, WNV antibody-enriched plasma, ribavirin, and Omr-IgG-am. Overall, 5/11 (45%) patients died, 4 of whom were immunosuppressed.61112131415 In a case series of two SOT recipients with St. Louis encephalitis treated with interferon alfa-2b in combination with IVIG, both patients survived with minimal to no residual neurologic deficits.5

An unblinded randomized controlled trial of patients with WNV neuroinvasive disease suggested greater neurologic improvement in 15 patients who received interferon alfa-2b compared with 8 patients who received supportive care only.16 In an open label safety/efficacy trial of interferon alfa-2b to treat patients with St. Louis encephalitis, treated patients (n=15) appeared to have better muscle function and respiratory control compared with 17 untreated patients, but the study design did not control for initial differences between groups.17 In both studies, treatment with interferon was associated with transient neutropenia and hepatitis that resolved after treatment was stopped.

Ribavirin

In two case reports of patients with WNV neuroinvasive disease treated with ribavirin, one SOT recipient who also received IVIG,6 and one child with Hodgkin’s lymphoma treated with ribavirin alone,18 both patients survived. In a case series of 233 patients hospitalized with WNV disease in Israel, 37 patients received ribavirin. Patients who received ribavirin were more likely to die (41%) compared with those who did not (9%), though patients who died were more likely to have evidence of more severe disease (i.e., encephalitis) and be treated with ribavirin than those who survived. In the multivariable analysis, ribavirin was not an independent risk factor for death.19

Corticosteroids

A systematic review and meta-analysis was performed to evaluate the use of corticosteroids for the treatment of viral encephalitis. Ten cohorts were included in the metanalysis, involving patients with multiple different viral pathogens (a subset of whom had WNV and other flaviviruses). No benefit of steroid therapy on survival was observed.20

A retrospective observational study described 65 patients with WNV neuroinvasive disease, 33 of whom received steroids during hospitalization (mean dose in mg of dexamethasone, 13.6 mg/day). There were no differences observed for in-hospital mortality (12% in each group) or neurologic sequelae at discharge between patients treated with steroids compared with those who did not receive steroids.21

In case reports and case series of patients treated with steroids for various WNV-associated neurologic manifestations (encephalitis, acute flaccid paralysis, ocular manifestations, brachial plexopathy), no deaths were reported; neurologic improvement was variable with gradual and partial improvement in some cases. Specific steroids used, dosing, and duration differed among reports.2223242526

Therapies studied but not currently available in the United States

Omg-IgG-am (Omrix Biopharmaceuticals, Tel Aviv, Israel): polyclonal IVIG product containing high titers of WNV neutralizing antibodies

In a phase 1/2 randomized, double-blind multicenter study, 62 participants with WNV neuroinvasive disease were randomized to receive Omg-IgG-am, polyclonal IVIG with no detectable WNV IgG antibodies, or saline. There were no significant differences in the primary endpoint of medication safety or in the secondary endpoints of morbidity and mortality, although the study was underpowered to assess efficacy outcomes and to detect rare serious adverse events.27

In case series and case reports involving 14 patients with WNV disease treated with Omr-IgG-am, 12 patients had neuroinvasive disease, 3 were SOT recipients (one viremic but asymptomatic), and 2 had chronic lymphocytic leukemia. Doses ranged from 400-500 mg/kg/day for variable durations, and 2 patients also received other treatments for WNV disease. Overall, 4/14 (29%) died.9282930313233

MGAWN1 (WNV recombinant humanized monoclonal antibody): a high-affinity humanized monoclonal antibody that targets the E protein of WNV

In a phase 1 safety and pharmacokinetics dose-ranging study, among 30 healthy adults who received MGAWN1, 6 experienced 11 adverse drug-related events, vs. none of the 10 participants in the placebo arm.34

In an unpublished clinical trial, 13 patients with WNV disease were randomized to receive a single infusion of MGAWN1 or placebo. Two of 6 patients in the MGAWN1 arm died compared with 1 patient who received placebo. This study was terminated due to a lack of study enrollment. ClinicalTrials.gov Identifier: NCT00927953 ()