By Bruce Buckley

Originally published by our sister publication, Specialty Pharmacy Continuum

In the spring of 2020, Children’s Hospital New Orleans began using high-dose immunoglobulin (IG) therapy along with other immunomodulatory drugs to treat pediatric patients presenting with severe systemic inflammation similar to that of Kawasaki disease, according to Ken Paris, MD, MPH, an associate professor of pediatrics at LSU Health Sciences Center New Orleans and the hospital’s clinical service line chief for allergy and immunology.

The disease was MIS-C, or multisystem inflammatory syndrome in children. It was occurring in kids as young as 6 months of age in the weeks following COVID-19 infection or exposure to the virus, said Dr. Paris, who spoke on pediatric IG therapy at the recent IgNS 2021 Conference, in Las Vegas.

Dr. Paris cited the MIS-C outbreak as one example of clinicians’ “highly varied” use of Ig therapy in the pediatric population, from primary immune deficiency and immune thrombocytopenic purpura to replacement therapy for patients undergoing chemotherapy and before and after bone marrow transplants.

“In practice, we see patients of all ages with immune deficiencies,” he said. “We meet them as children but keep them throughout childhood, adolescence and into adulthood. If we make a diagnosis early on,” he added, “we can prevent complications and organ damage that can occur after a lifetime of infection or inflammation within the lungs, such as bronchiectasis.”

Pediatric patients are more likely than adults to be eligible for a definitive treatment of their disease, Dr. Paris said. “In the last three months,” he said, “we’ve identified four patients that we referred to our bone marrow transplant specialists for stem cell transplants. We don’t see that in our adult patients, who tend to have more complex disease because of a lifetime of inflammation and damage.”

He pointed out that children who are identified early in life, before complications set in, are more likely to have multiple sources for stem cells based on their physical size.

For certain patients, Dr. Paris said, “and I don’t say this to everybody I care for, there is really hope for disease resolution or even a cure in the future.” One reason for hope, he added, is due to the developmental changes that occur within the immune system.

Because the immune system develops differently over time, Dr. Paris said, “the interventions we prescribe to individual patients may be different based on their age. For a 2-year-old in my practice who has a mild IgG deficiency, some recurrent infections but otherwise has a normal workup, I might elect to treat with prophylactic antibiotics or watchful waiting, expecting that that IgG will come up over the next six months or a year. And I’ll be able to make the diagnosis of transient hypogammaglobulinemia of infancy.”

He added: “If the same situation occurred in a 28-year-old, I might have a different therapeutic option, because treating with antibiotics alone might not be the right choice. It’s unlikely that some major change is going to happen, and that patient is going to miraculously start to develop a better production of IgG or respond to vaccines over the next couple of years. So, I might pull the trigger on replacement therapy with immunoglobulin a little bit sooner.”

Not a One-Time Decision

Choosing IG replacement therapy isn’t a one-time decision, Dr. Paris noted. It requires constant adjustment, especially in the pediatric population. He used the example of a patient in his practice diagnosed with X-linked agammaglobulinemia at 6 months and weighing 15 to 18 pounds. “Over the next so many years, how many dose adjustments will need to be made based on their weight and growth?” he asked.

To make those adjustments, he continued, requires “a huge fund of knowledge” on the part of physicians, nurse practitioners, infusion nurses and pharmacists. “They need to know about adverse events associated with different products. They need to recognize the comorbidities present in different diseases. They have to understand the different product characteristics and the equipment utilized based upon age and different needle lengths. Unfortunately, specialty health care providers in the pediatric world are few and far between.”

In response to a question about the challenges of diagnosing immunodeficiency in children, Dr. Paris noted that delays occur, primarily because immunodeficient children typically have the same infections as normal children, “just at a more frequent rate. Over time, though, we’ve done better at educating pediatricians to recognize immune deficiencies,” he said.

He added: “Newborn screening has been huge in advancing diagnosis down to the first weeks of life. Many patients who previously would have been missed are being picked up. We can do rapid-turnaround genetic tests pretty early for not a whole lot of money.

“But for adults, it’s hard,” he continued. “If you’ve gotten to age 30 without someone recognizing an immune deficiency, it’s because it’s not obvious. That’s why you get delays in diagnosis. It’s the subtlety of a lot of immunodeficiency diseases. They don’t scream, ‘I have a problem!’”

Dr. Paris is a member of the Takeda advisory board and a speaker for Takeda.