By Amna N. Ahli and Philip R. Fischer, MD, DTM&H
Amna N. Ahli is a medical student at Khalifa University and Sheikh Shakhbout Medical City in Abu Dhabi, United Arab Emirates. Dr. Fischer is Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN; Department of Pediatrics, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates.
SYNOPSIS: Despite concerns about the use of infliximab for children with Kawasaki disease shortly after administration of live vaccines, retrospective reviews do not show any vaccine-related infections following subsequent infliximab use.
SOURCE: Ohnishi Y, Okada S, Kawakami-Miyake A, et al. Safety and feasibility of infliximab therapy in children with Kawasaki disease who received live vaccinations. Pediatr Infect Dis J 2022;41:e388-e392.
Infliximab is an effective treatment for children with refractory Kawasaki disease that has not responded to intravenous immune globulin and aspirin. However, use of infliximab, as a monoclonal antibody that binds to tumor necrosis factor alpha, could presumably either increase the risk of exacerbating a co-existing virus infection or reduce the body’s production of protective effective antiviral antibodies. Practically, there is concern that vaccine-related infections could cause severe disease if infliximab is given shortly after live virus vaccination.
Thus, to evaluate the safety and efficacy of infliximab therapy in children with Kawasaki disease who received infliximab within a few months of a live agent vaccine, researchers in Japan reviewed their experience with infliximab for Kawasaki disease.
Ohnishi and colleagues reviewed findings from 365 Kawasaki disease patients treated at a single hospital from 2011 through 2020. The diagnosis followed standard diagnostic criteria. Patients were categorized as having received a live virus vaccine within three months or a Bacillus Calmette-Guerin (BCG) vaccine for tuberculosis within six months prior to use of infliximab. Those who received infliximab already had received two cycles of intravenous immune globulin and were taking aspirin. Antibody titers against vaccine viruses were tested.
Most patients had not received a live vaccine during the months prior to developing Kawasaki disease, but 48 patients had. Of those 48, eight went on to require and receive infliximab. The eight children who were vaccinated during the few months prior to infliximab use had received BCG vaccine 70-144 days prior to infliximab (three children), varicella vaccine 40-76 days prior to infliximab (two children), measles and mumps and rubella and varicella vaccines 69 days (one child), measles and mumps vaccines (one child), varicella vaccine (two children), and rotavirus vaccine (one child). Infliximab-treated patients who had recently been vaccinated achieved similar outcomes to those who had not been vaccinated. There were not any apparent vaccine-associated infections. Anti-vaccine virus antibody titers were noninferior in the infliximab treated group to those who had not received infliximab.
The concern that prompted the study was that use of infliximab shortly after live virus vaccines and/or BCG would lead to severe vaccine-related infections. This study, although with small numbers, found no evidence of either infectious complications related to pre-infliximab live vaccine or altered vaccine responsiveness.
The authors rightly point out that their patients had received intravenous immune globulin prior to infliximab use and that this might have altered risks of subsequent vaccine-related viral infections. Thus, the lack of identified adverse outcomes with infliximab shortly after vaccination in this study does not necessarily guarantee that short durations between live vaccines and infliximab would be safe in other settings where other diseases are being treated (without intravenous immune globulin being given).
COMMENTARY
Pediatricians usually are aware that live vaccines can lead to dangerous infections in immunocompromised children. The converse — that use of immunocompromising agents after live vaccine administration might also cause problems — is less often considered.
In Japan, where this study took place, routine guidance is that infliximab should not be administered within three months of receiving a live virus vaccine or within six months of receiving a BCG vaccine. The authors of the study noted that rheumatology and British guidelines suggest shorter minimum durations of delay between live vaccines and infliximab use than do the Japanese guidelines. These new data are consistent with the safety of durations of one to two months between live vaccines and infliximab initiation (if not even shorter).
Two years ago, postmarketing surveillance in Japan identified 17 patients who had received infliximab less than three months after live vaccine administration; none developed vaccine-related infections or complications.1 In a U.S. review, 38 patients had received live vaccines less than three months prior to receiving infliximab for Kawasaki disease (14 of them within 30 days); none had a serious infection as a consequence of the treatment.2
Of course, these Kawasaki disease-related data about vaccination prior to infliximab use do not imply that vaccination after infliximab is necessarily safe. A systematic review of babies born following in utero exposure to biologic agents used to treat rheumatologic disease demonstrated that eight of 215 biologic-exposed children had adverse reactions after BCG vaccination, with one death.3
REFERENCES
- Miura M, Kobayashi T, Igarashi T, et al. Real-world safety and effectiveness of infliximab in pediatric patients with acute Kawasaki disease: A postmarketing surveillance in Japan. Pediatr Infect Dis J 2020;39:41-47.
- Lee AM, Burns JC, Tremoulet AH. Safety of infliximab following live virus vaccination in Kawasaki disease patients. Pediatr Infect Dis J 2017;36:435-437.
- Chua N, Parker E, Giles I, Goulden B. A systematic review of live vaccine outcomes in infants exposed to biologic disease modifying anti-rheumatic drugs in utero. Rheumatology (Oxford) 2022;Mar 8;keac141. [Online ahead of print].
Despite concerns about the use of infliximab for children with Kawasaki disease shortly after administration of live vaccines, retrospective reviews do not show any vaccine-related infections following subsequent infliximab use.
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