Live vaccines and biologics for asthma

To my knowledge there is no data that clearly describes specific risk factor of live vaccines condonement with Dupilumab, Mepolizumab or Xolair use. My understanding is that when the studies were done use of live virus vaccine was an exclusion. So, because of that exclusion in the original studies, the FDA required that statement in the PI. Simply put, we don’t know. Dr Casale did substantial research of these biologics, so I reached out to him. Dr Casale’s response: “I have heard of no contraindications of administering vaccines in patients treated with these biologics.”

Dr Ledford provided a very thoughtful response to a very similar question in Ask the Expert, 7/25/17.

Dr Ledford’s response:
I am not aware of an increased risk of herpes or varicella with dupilumab although severe atopic dermatitis is a risk for herpetic infections. A review of the 13 published trials as of 2016 found that skin infections overall were decreased with dupilumab (1). The pivotal trials (SOLO 1 and 2) excluded live virus vaccines for 12 weeks prior to the study for general safety rather than because of an increased risk with dupliumab (2). The adverse events during the 2 studies report herpes infections in both placebo and dupilumab treated subjects without convincing evidence of increased occurrence with dupliumab (1% with placebo vs 3% with every other week dupilumab and 1% with weekly dupilumab in SOLO 1 and 1 case with placebo, 0 with dupilumab every other week and 1 case with weekly dupilumab in SOLO 2). There were no reports of shingles during the trials. The prescribing information for dupixent does not recommend live virus vaccines during treatment but provides no references as to why. There is a theoretical concern that inhibition of IL-4 and IL-13 may impair immune response, probably more likely humoral response but also may affect T cell responses. Vaccine response to tetanus and meningococcus was not affected (3). There are no studies with live virus vaccines.

I shared your question with Dr. Tom Casale, a recognized expert on the development of monoclonal therapies for allergic disease. He did not feel that the risk of live viral vaccination is based upon any data but is rather a precaution.

In summary there is no evidence of increased risk of infection with dupilumab and no specific rationale to avoid live viral vaccines during treatment, but it is stated in the prescribing information. Atopic dermatitis is a risk factor for herpetic infection. Prior to beginning dupilumab, I would administer the shingles vaccine, as it is approved over the age of 50 years. However, many health plans do not cover shingles vaccine until the age of 60 years. If this is the case for your patient, I would not delay the dupilumab, and hopefully the viral component shingles vaccine, containing no viable virus, will be available by the time your patient becomes 60 years of age (4).

1. Blakely, Kim, Melinda Gooderham, and Kim Papp. "Dupilumab, a monoclonal antibody for atopic dermatitis: A review of current literature." Skin Ther. Lett 21 (2016): 1-5.
2. Simpson, Eric L., et al. "Two phase 3 trials of dupilumab versus placebo in atopic dermatitis." New England Journal of Medicine 375.24 (2016): 2335-2348.
3. Highlights of Prescribing Information

I hope you have found this helpful.
Special thanks to both Dr Ledford and Dr Casale for their insights on this issue.

Respectfully submitted
Jeffrey Demain, MD, FAAAAI