Using Biologic Therapies Safely in Pediatric Patients With Skin Conditions

Treating pediatric patients with biologic therapies presents challenges, according to a session at the Society for Pediatric Dermatology Annual Meeting, held in Toronto, Ontario, Canada, between July 11 and July 14, 2024. The session, held on the last day of the conference, featured talks on the use of vaccines while on biologics and the dose and duration of using biologics.

Vaccine Use for Children on Biologic Treatment

The session began with Stephen R. Humphrey, MD, FAAD, associate professor of dermatology at the Medical College of Wisconsin, who highlighted considerations pediatricians should take when giving vaccines to patients on biologic therapies. Biologic therapies, such as adalimumab, are immunosuppressants, which could leave patients vulnerable to infections and live vaccines.

“As we are prescribing a lot of immune-suppressive medications, it’s really our responsibility to engage with our primary care providers, who are giving the vaccines typically, to have the best plan for our patients,” said Humphrey.

He recommends, in general, trying to give at least 1 dose of the vaccines prior to starting a patient on the biologic medication. This would include giving a live vaccine about 4 weeks prior to biologic treatment and inactivated vaccines about 2 weeks prior to treatment. Inactivated vaccines may be given to a pediatric patient while on the biologic treatment, but they could have a reduced immune response and may not produce the desired effect of the vaccine.

Humphrey also recommended checking hepatitis B titers before starting either rituximab or anti–TNF-α inhibitors, as patients with inflammatory skin conditions may have lower immunity than other patients. Consider the possibility of reactivating latent hepatitis B and making a plan based on the individual risk of the patient.

“Inactivated vaccines can be given while on a high- or low-dose immunosuppressive therapy so just follow that childhood immunization schedule,” said Humphrey. This includes the pneumococcal extra vaccine for patients aged 2 years and older. “You should not be withholding vaccines because we’re worried their atopic dermatitis is going to flare or we’re worried that their psoriasis is going to flare. I’m sure we all have patients with specific skin conditions where they did flare a little bit after vaccines but really you should still be pushing to get vaccines.”

Live vaccines could be considered while on a TNF-α inhibitor, said Humphrey. When a patient is on rituximab, live vaccines should be administered after a 4-week delay whereas non–live vaccines, such as influenza, can be given on schedule. Both should require B-cell counts to normalize and non-live vaccines should require the delay of rituximab for 2 weeks after administration. There is not a lot of evidence on IL inhibitors, but experts recommend discontinuing for 2 to 3 half-lives before administration of live vaccines and no discontinuation for non–live vaccines.

Humphrey presented the results of a post-hoc analysis¹ that tested the safety of using live vaccines on patients using dupilumab, with 1 group continuing the treatment and the other group discontinuing. “What they found is that for both groups, in the small number, that all of them did not have any issues with the vaccines,” said Humphrey.

Humphrey concluded by saying that shared decision-making should be the baseline for administering vaccines to patients on biologics. “Talk about vaccines with them, have an honest conversation, engage with them, talk with your pediatrician or family practice doctor, and then take it case by case,” he said.

Dosing and Duration in Biologics

Elaine Siegfried, MD, professor of pediatrics and dermatology at St. Louis University School of Medicine, discussed the dosing and duration of treating pediatric patients with biologics. “This is a question that we all kind of have about how do you dose these things? Is it just strictly on label? Can you vary off of that? When to increase, when to stop…,” she began.

Changing a dose of a biologic requires a dermatologist to think about other reasons for suboptimal response to the biologic. This can include poor adherence, interval weight gain, and complicating factors like secondary allergic contact dermatitis, systemic contact dermatitis, and psoriasis skewing.

Siegfried said that you have to wait about 16 weeks before considering to change the dose of the biologic. Biologics don’t have any associated safety signals, she said, so increasing the dose can be done safely. Increasing the dose can look like increasing it from 200mg to 300mg or increasing the frequency of the dose.

Siegfried also discussed when to taper or stop the dose of the biologic for pediatric patients. “I’m here to say that I have a lot of kids who have successfully…gotten off treatment,” she said. After asking the rest of the audience how many of them had gotten a patient off treatment, more than half of the audience had reported such an occurrence, which Siegfried remarked was “very, very heartening.”

Establishing what remission looks like is the first step to determining whether the patient can get off of treatment. Clinical remission on the drug could involve minimal disease that does not affect daily life and clinical absence of the disease for an extended period of time, likely 1 year or longer. Therapy-free remission off the drug can include the clinical absence of the disease for an extended period that includes negative relevant and validated biomarkers. Siegfried acknowledged that these biomarkers will have to be looked into in the future.

When in remission on treatment, tapering can be done by decreasing the dose from 300 mg to 200 mg or increasing the time between the injections. Siegfried said that 8 weeks is usually the amount of time that is recommended between injections while tapering before attempting discontinuation.

The incidence of children being able to achieve therapy-free remission is higher in children who started therapy earlier based on emergent data but Siegfried concluded by saying that additional subset analysis is needed in these children to determine whether therapy-free remission is possible in children who start treatment at a very young age and who achieve clear skin rather than almost clear skin.

Biologics are an important tool in treating patients with skin conditions. Making sure that they are being used in the way best suited to the pediatric patient’s safety and dosed correctly is important in making sure that the patient gets the most out of their treatment.

References

Weschler ME, Souza-Machado A, Xu C, et al. Preclinical and clinical experience with dupilumab on the corelates of live attenuated vaccines. J Allergy Clin Immunol Glob. 2022;1(1):9-15. doi:10.1016/j.jacig.2021.12.003