By Gina Shaw
Anticipated shortages of intravenous immune globulin (IVIG) as a result of fewer plasma donations during the COVID-19 pandemic have yet to occur, but experts say it’s likely these shortages have only been delayed by a corresponding decreased demand for IVIG during the past several months. 

“A top IVIG manufacturer told me recently that they think it looks like our U.S. supplies will be OK through the end of January, but what things look like thereafter is still to be determined. It’s a very dynamic situation,” said Patrick Schmidt, the CEO of FFF Enterprises, a leading national wholesaler of plasma products.

On Nov. 4, 2020, the Plasma Protein Therapeutics Association (PPTA), which represents more than 860 human plasma collection centers in the United States and Europe, issued a statement warning of an urgent need for plasma donation. “Reports vary, but plasma collectors experienced significant declines in collections due, in part, to the impacts of social distancing measures and other mobility restrictions caused by the COVID-19 pandemic,” the statement said. “Considering the complex manufacturing of plasma-derived therapies can take 7-12 months, any decline in plasma donations could impact patients’ ability to access their lifesaving therapies. This sharp decline in plasma collections currently being experienced could cause more significant challenges in the months to come.”

Schmidt said donations at plasma centers in Texas’ Rio Grande Valley were particularly hard hit by the pandemic. “Based on what the manufacturers are telling us, as of mid-May, donations in that region were down by about 62% compared with the same period in 2019. Donations overall nationwide were down by about 51% for that time period. There was a bit of a resurgence in donations over the summer when cases were down, but now we’re in a much more difficult time and donations will likely decline again.”

Clinicians who care for patients requiring IVIG therapy say shortages have not yet affected their patients, but they believe that is in some part due to the fact that, just as plasma donors have avoided donation centers during COVID-19-related quarantines, some patients have missed doses during the pandemic. “Plasma collection is down, but there has been a corresponding decrease in the use of IVIG products during the pandemic,” said Eric Tichy, PharmD, MBA, the vice chair of supply chain management at Mayo Clinic, in Rochester, Minn. “When people miss these doses, they don’t get additional doses later on. They just get missed. So far, we are in a pretty good position from an IVIG inventory standpoint.”

But that could change, because other factors might drive up usage of plasma products, Tichy noted. In addition to the development of convalescent plasma treatments for COVID-19, Tichy wonders about new indications for IG in the treatment of the disease’s long-term neurologic effects. “For example, the Kawasaki-like disease in children,” he said. “If data were to emerge showing that IG treatments helped with that, it could further increase the use of IG.”

Driving Up Use

Bhavesh Shah, MD, the senior director of specialty pharmacy strategy and market access and hematology-oncology pharmacy at Boston Medical Center, agreed that several factors might drive up use of plasma products. But at the present time, he noted, there is no cause for alarm. 

“We haven’t experienced any supply issues so far,” he said. Given the length of the manufacturing process for IVIG, Shah said he would have expected any shortages resulting from declining plasma donation levels due to the pandemic, which first hit the United States in March, to start becoming noticeable by November or December. “This has not happened yet, which could be because patients concerned about going out and possibly being exposed to the virus were extending their doses to every eight weeks, for example, when they were supposed to get IVIG every four weeks,” he said.

“Of course, the numbers of newly diagnosed patients were down, because the diagnoses for IVIG indications like PID [primary immunodeficiency] and CIDP [chronic inflammatory demyelinating polyneuropathy] need to be made in person, utilizing bone marrow biopsy, neurologic testing and other resources that cannot be done via telehealth. So, there has been a lower volume of patients getting new starts of IVIG.”

Shah said he remains watchful, however. “Hospitals are now overwhelmed in many areas of the country, so you’re likely getting even more reduced levels of plasma donations in many states. Since things were not as locked down over the summer, there were probably more patients with conditions like CIDP and PID getting diagnosed or resuming treatment schedules they had missed, so we may see supply issues in six to nine months. I wouldn’t discount the potential for COVID-related shortages until we’ve made it through the spring.”


Ensuring Rational Use

In the meantime, Shah urged prescribers and pharmacies to continue rigorous utilization management of IVIG, particularly given that the use of these products continues to increase with new indications, the aging of the population, and more diagnoses of primary immunodeficiencies and neurologic conditions (Am J Manag Care 2019;25[6 suppl]:S105-S111). “It’s important to ensure that the indication for which you are using IVIG has appropriate evidence behind it,” he said.

To that end, he directed clinicians to a 2017 review by a work group at the American Academy of Allergy, Asthma and Immunology (AAAAI). The review summarizes the evidence for both subcutaneous immune globulin and IVIG indications (J Allergy Clin Immunol 2017;139[35]:S1-S46). The AAAAI also offers principles for the effective use of IVIG for patients with PID.

Shah offered some additional IVIG conservation tips:

Don’t hoard! That will only make matters worse. “There’s going to be some cannibalization of supply as people recall their difficulties with previous shortages,” Shah said. “I’ve heard rumblings that home infusion providers and specialty pharmacies are buying up supplies of plasma products.”

Reevaluate utilization more stringently. “We know that ideal body weight [IBW] is just as effective as actual body weight for IG dosing,” he said. “If we were to use IBW for everyone in the country, that would decrease consumption by 20%, or 20 million grams of IG.”

Be careful about off-label use. For many immunodeficiencies, IG is the primary treatment option, and there are few viable alternatives. To preserve supplies for these patients, consider other treatments for conditions in which IG is used off-label. “For example, in the setting of polymyositis and dermatomyositis, there are other immune modulators that can be used,” Shah said.

Consider extending dosage frequency. “We have a traditional mindset where IVIG has to be given every four weeks,” Shah said. “For some indications, we can extend the frequency to every six to eight weeks, or even every two to three months. These decisions need to be made on a case-by-case basis.”