hIVIG Leads to Significant Benefit for Patients with Influenza B

An international trial known as FLU-IVIG has found that the addition of anti-HIV immune globulin (hIVIG) to standard care for patients with influenza B had both a significant benefit at day 7 and a significant virological benefit at day 3 compared with placebo. Furthermore, researchers found that passive immunotherapy as an adjunctive treatment for adults hospitalized with severe influenza A does not provide clinical benefit.

The double-blind, placebo-controlled trial was designed and conducted by the International Network for Strategic Initiative in Global HIV trials (INSIGHT). Approximately 313 patients were enrolled in 34 sites between 2014 and 2018, with 168 patients randomly assigned to the hIVIG group and 161 to the placebo group.

The researchers examined outcomes that included the primary 6-category outcome on days 14 and 28; the primary 6-category outcome on days 1 through 7; time to discharge, time to death, and national early warning (NEW).

On the basis of the favorable pharmacokinetics and hemagglutination inhibition titres measured during a pilot trial, hIVIG was given at a dose of 0.25 g/kg/ dissolved in as much saline as needed to reach a total volume of 500 mL. A single infusion was given as soon as possible after randomization over a period of approximately 2 hours. Three-hundred and two patients were infused on the day of randomization and 6 were infused on the day after randomization.

In subgroup analyses for the primary outcome, the ordinal outcome in patients with influenza A was 0·94 (0·55—1·59) and was 3·19 (1·21–8·42) for those with influenza B (interaction p=0·023). After 28 days of follow-up, 47 of 156 patients in the hIVIG group and 45 of 152 patients in the placebo group had the composite safety outcome of death, a serious adverse event, or a grade 3 or 4 adverse event.

The proportion of patients with influenza A ranged from 64% recruited between 2016-2017 and 87% recruited between 2013-2014 over the 5 seasons of enrollment. The median number of days since symptom onset at entry was 3. Approximately 256 of the 308 evaluable patients were randomly assigned to groups on the date of screening and for these patients, the baseline and eligibility NEW scores are identical. The remaining 52 patients were screened on the day before randomization, and for these patients the baseline NEW score could have decreased below 2 points.

This trial provided strong evidence that passive immunotherapy as an adjunctive therapy for adults hospitalized with severe influenza A does not provide clinical benefit. Although the beneficial effect of hIVIG for patients with influenza B is supported by the antibody affinity analyses done on the lots of the study drug, confirmation of clinical and virological benefit is warranted in a further randomized controlled trial enrolling participants hospitalized with influenza B.

Reference

• Davey R, Fernández-Cruz E, Markowitz N, et al. Anti-influenza hyperimmune intravenous immunoglobulin for adults with influenza A or B infection (FLU-IVIG): a double-blind, randomised, placebo-controlled trial. The Lancet. Published September 30, 2019. https://doi.org/10.1016/S2213-2600(19)30253-X. Accessed October 21, 2019.