One pill to help not get ill.
Baloxavir (trade name Xofluza) was approved for the treatment of acute, uncomplicated influenza in patients > 12 years of age in October 2018. However, high-quality data has been underwhelming at best for its efficacy in treatment.
Consistent with every other study on anti-viral medications for influenza, baloxavir appears to decrease duration of symptoms. This is especially true in patients treated within 24 hours of symptoms. However, there are some important points to consider when evaluating the evidence for baloxavir:
- Cost of the medication
- Increased resistance after initiation
- Results only applicable to H3N2
- No comparison to standard care (i.e. symptom-based therapy)
- Studies were pharma sponsored
- No patient-oriented outcomes
Despite the reduction in symptoms, for all of the reasons above it is hard to make an argument for the use of baloxavir in patients with confirmed influenza.
Continued research on effective anti-influenza drugs is critically important particularly with the potential for a “double pandemic” in the coming months (COVID-19 and Influenza). It’s already bad enough getting one or the other but getting both at the same time could be potentially disastrous. While treatment results are modest at best, baloxavir has potential as a prophylactic medication as well.
Article: Ikematsu H et al. Baloxavir Marboxil for Prophylaxis Against Influenza in Household Contacts. NEJM 2020: 383(4): 309-20. PMID: 3260124
This was a multicenter, double-blind, randomized, placebo-controlled trial performed in Japan. Household contacts that had no influenza symptoms (including fever) and lived in the same household as the index patient (positive rapid influenza test) for at least 48 hours before enrollment were included in the study.
The query was simple: Does a single dose of baloxavir to asymptomatic, close household contacts reduce the development of clinical influenza in this group in comparison to placebo? The primary outcome of the study was laboratory-confirmed clinical influenza (RT-PCR positivity for influenza virus RNA and the presence of both fever and at least one respiratory symptom of moderate or greater severity during the period from day 1 to day 10). Patients were given a single, weight-based (<80kg; 40mg and ≥80kg; 80mg) oral dose of baloxavir and compared it to matching placebo.
Overall there were 545 index patients of which ≈75% were <12 years of age. The majority (≈96%) of index patients had influenza A (H1N1 and H3N2), ≈30% had influenza vaccination in the previous six months, and all index patients were treated with anti-viral medications. This is not typically done in clinical practice.
There were 749 household contacts of the index patients who did not have symptoms of influenza enrolled for treatment. Almost 20% of these patients were <12 years of age and ≈3% were >65 years of age. In this group, influenza vaccination within the last six months was also around 30%.
Looking at the primary outcome, the use of baloxavir reduced lab confirmed clinical influenza in household contacts of index patients (1.9% vs. 13.6%). This is a number needed to treat of 8.5. There was no difference in adverse events between groups.
Important Points About this Trial:
- All index patients were treated with antivirals, which is not standard practice in many areas and may limit generalizability of the study results.
- The study almost exclusively looked at influenza A (H1N1 and H3N2) and the results can only be applied to outbreaks of this influenza type.
- Patients with significant chronic illness, pregnant women and patients age ≥65 years were either excluded or a minimal number of the patients included.
- Only 1/3 of the population was vaccinated for influenza. These results could be more profound in lesser vaccination areas or less robust in areas with more influenza vaccination. These results will also be dependent on the success of the vaccination itself for the given year.
- About 75% of the index patients in the trial were ≤11 years of age while 70 to 75% of the contact patients were 20 to 64 years of age. Assessment of symptoms was significantly different for patients older than 12 and younger than 12.
- Positive testing required a 99.5 temp (which technically isn’t even a fever) plus “moderate” or “severe” symptoms. Can 12- to 13-year-olds (or even adults) reliably make this mild/moderate determination?
- Index patients were diagnosed with rapid influenza testing while contacts were tested with RT-PCR. Even the CDC notes that presence of viral RNA on PCR testing does not mean that an active infection or even a viable virus is present.
Single-dose baloxavir may be a useful prophylactic medication to prevent additional clinical infections in close household contacts. Based on this data, we only have an established benefit when the index patient has influenza A (the 2020 influenza season appears to be dominated by influenza B). The role of baloxavir for prophylaxis in those who are immunized as well as in those with significant comorbid disease is unknown.