As medicine and science advances, pediatric clinicians are seeing ever increasing numbers of approved immunomodulatory therapies approved by the US Food and Drug Administration (FDA). A few examples of drugs approved in recent years include emapalumab (Gamifant) for primary hemophagocytic lymphohistiocytosis and the expanded approval for tocilizumab (Actemra) for cytokine release syndrome due to chimeric antigen receptor T-cell therapy.
Additionally, clinicians may see increased use of older agents such as anakinra (Kineret) for off-label indications such as macrophage activating syndrome and, of course, there are numerous agents once reserved for use in adult populations that are making their way into the world of pediatric medicine.1 Given this increased prevalence and current state of vaccine compliance within the United States, general practice physicians may find themselves wondering how to best protect patients who previously received an immunomodulatory agent from vaccine-preventable diseases.
State of current knowledge
Whereas many of these therapies are being used in an acute care setting, it is important to remember that immunomodulatory therapies new and old can have ramifications on the immune system for weeks to months after administration. The problem of how to vaccinate children receiving these immunomodulatory agents is being increasingly recognized as evident by the development of guidelines from bodies such as the Infectious Diseases Society of America and the Canadian Paediatric Society.2,3 Both guidelines stress the importance of obtaining vaccination records and vaccinating if at all possible before starting immunomodulatory therapies.
In the case of patients receiving immunomodulator therapy for a stable, chronic condition, it is likely feasible to postpone therapy while live vaccines are completed. Immunosuppressed patients receiving chemotherapy or after bone marrow transplants will likely be under the care of an oncologist and may need to undergo revaccination according to their practice’s protocol. Unfortunately, not all children will fall neatly into either of these categories.
Currently, published guidelines do not address how to modify or return to a child’s normal immunization schedule after therapy has been completed. In a small but growing population of patients, these therapies are not chronically administered, and patients may have already returned to the routine care of their primary care provider. It is critical that primary care providers are fully informed of when such therapies were administered. This overview aims to highlight established recommendations for selected agents and reveal knowledge gaps where specialty guidance may be warranted.
1. Rajasekaran S, Kruse K, Kovey K, et al. Therapeutic role of anakinra, an interleukin-1 receptor antagonist, in the management of secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction/macrophage activating syndrome in critically ill children. Pediatr Crit Care Med. 2014;15(5):401-408.
2. Rubin LG, Levine MJ, Ljungman P, et al; Infectious Diseases Society of America. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58 3):309-318. Erratum in: Clin Infect Dis. 2014;59(1):144.
3. Le Saux N; Canadian Paediatric Society, Infectious Diseases and Immunization Committee. Biologic response modifiers to decrease inflammation: focus on infection risks [article in English, French]. Paediatr Child Health. 2012;17(3):147-150.
4. American Academy of Pediatrics. Immunization in special clinical circumstances. In: Kimberlin DW, Long SS, Brady MT, Jackson MA, eds. Red Book: 2018-2021 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018:67.
5. Humira [package insert]. Abbott Laboratories; North Chicago, IL: 2011.
6. Kineret [package insert]. Swedish Orphan Biovitrum AB; Stockholm, Sweden: 2012.
7. Gamifant [package insert]. Novimmune SA; Geneva, Switzerland: 2018.
8. Remicade [package insert]. Janssen Biotech; Horsham, PA: 2013.
9. Actemra [package insert]. Genentech; South San Francisco, CA: 2013.
10. Rituxan [package insert]. Genentech; South San Francisco, CA: 2010.
11. Nazi I, Kelton JG, Larché M, et al. The effect of rituximab on vaccine responses in patients with immune thrombocytopenia. Blood. 2013;122(11):1946-1953.
12. Jeyaratnam J, Ter Haar NM, Lachmann HJ, et al. The safety of live-attenuated vaccines in patients using IL-1 or IL-6 blockade: an international survey. Pediatr Rheumatol Online J. 2018;16(1):19.
13. Croce E, Hatz C, Jonker EF, Visser LG, Jaeger VK, Bühler S. Safety of live vaccinations on immunosuppressive therapy in patients with immune-mediated inflammatory diseases, solid organ transplantation or after bone-marrow transplantation—a systematic review of randomized trials, observational studies and case reports. Vaccine. 2017;35(9):1216-1226.
14. Reich J, Wasan S, Farraye FA. Vaccinating patients with inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2016;12(9):540-546.