UnitedHealthcare beneficiaries fight for access to immunoglobulin

Jennifer Gabriel and Gina Jacobsen both know what living with primary immunodeficiency (PI) is like. Gabriel has unspecified hypogammaglobulinemia. Jacobsen’s son, Matthew, has X-linked agammaglobulinemia (XLA). Gabriel and Jacobsen also know how important regular immunoglobulin (Ig) replacement therapy is for treating these conditions and keeping infections at bay. Unfortunately, they have yet another experience in common—both Gabriel and Jacobsen’s son were forced into non-medical switching under UnitedHealthcare (UHC) insurance plans, a practice where stable patients are made to switch medications for non-medical reasons. 

Ig replacement therapy involves regular infusion, either intravenously (IVIG) or subcutaneously (SCIG), of antibodies purified from donated human blood plasma. These infusions give people with antibody deficiencies like hypogammaglobulinemia and XLA the antibodies their bodies can’t make to help them fight off germs. There are currently 17 Ig medications approved to treat PI in the U.S., none of which have biosimilars, or generics, available. In addition, though these products all contain antibodies, they are manufactured using different processes, with different stabilizers and inactive ingredients in the final products, and the American Academy of Allergists and Immunologists (AAAAI) has unequivocally stated that they are not interchangeable.

Immunoglobulin to the rescue

Gabriel had frequent infections as a teenager that weren’t taken seriously until college when she ended up with tonsils so swollen with dead tissue they had to be removed immediately. She mentioned to the hospital ear, nose, and throat specialist that she typically had six or seven sinus infections a year. He ultimately referred her to an immunologist and she was diagnosed with PI in 2017. Her immunologist prescribed Ig replacement therapy, the standard of care for someone with frequent infections and hypogammaglobulinemia, to prevent infections.

After initially trying monthly dosing with Hyqvia and still experiencing occasional infections, Gabriel switched to Cuvitru, a 20% Ig product that she used for SCIG every two weeks. 

“I think the switch from every four weeks to every two weeks ended up working better for me. My infections went down significantly, I stopped seeing my [ear, nose, and throat doctor] as much, I stopped having to go on as many antibiotics. I think overall, I was in much better shape,” Gabriel said about the switch.

Jacobsen’s son, Matthew, who is now 13, was diagnosed with XLA at seven months old after a scary, three-week hospital ordeal. “He was so ill we had him baptized in the hospital because we weren't sure whether or not he was going to survive,” Jacobsen said. After the diagnosis was finally made, doctors put him on IVIG immediately. “Once they administered the IVIG, my little guy who was on a feeding tube, whose skin was pale and white, who was not even moving, perked up within hours,” said his mother.

Matthew continued to receive IVIG through second grade. However, he missed a full day of school every three weeks because he had to receive his infusions at the hospital. As he got older, he and his parents made the decision to switch to SCIG so that he could self-infuse at home, decreasing absences from school.

“The first medication we tried was Hizentra and he had a site and allergic reaction to that one, which caused a rash, high fever, and local site pain for several days,” Jacobsen said. Like Gabriel, Matthew switched to Cuvitru and had been infusing for several years with no issues—until recently.

Access blocked under UnitedHealthcare insurance plans 

Starting October 1, 2023, UHC dropped four immunoglobulin (Ig) products from the majority of its plans: Asceniv, Cuvitru, Cutaquig, and Panzyga. Alarmingly, these products were not just dropped from UHC’s preferred drug list (also known as a formulary) but from the majority of UHC plans altogether. UHC declared that the medications were not medically necessary for the treatment of any condition, despite the fact that all four are Food and Drug Administration (FDA)-approved to treat PI and Panzyga is also FDA-approved to treat the autoimmune disorder chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). 

IDF reached out to UHC for clarification on how these medications were determined to be not medically necessary. UHC said in a provided statement, “We cover 13 FDA-approved immunoglobulin therapies to treat primary immunodeficiency. Each of these therapies are therapeutically equivalent—defined as similar efficacy and adverse events—as determined by the UnitedHealthcare Pharmacy & Therapeutics Committee based on review of clinical literature and trials and in consultation with external specialist physicians. External practicing physicians constitute the majority of the Pharmacy & Therapeutics Committee.” 

IDF also asked how being ‘off-plan’ affects the ability of beneficiaries to appeal denials for these medications, but UHC did not respond to that question. 

When Gabriel switched to Cuvitru in 2020, she was on her father’s UnitedHealthcare Choice Plus plan and had no issues getting prior authorization. In 2022, she moved to her employer’s health plan, also UnitedHealthcare Choice Plus, and also did not have any issues getting prior authorization for Cuvitru. It was only this past fall that she received notice that Cuvitru was no longer covered. 

After UHC’s notice, Gabriel and her doctor filed an appeal to keep her on Cuvitru. They also scrambled to identify an alternative and get the necessary prior authorization from UHC to start the new medication. That’s when the bureaucratic issues began. Gabriel’s prior authorization for Hizentra, another 20% SCIG product, was delayed because, paradoxically, she still had a prior authorization for Cuvitru pending. 

“I've missed a couple of infusions during the process, like during the holiday season, which, you don't wanna be missing [infusions] during that time with all the travel and everything,” she said. “I missed like two infusions because of just all the mix up and trying to get [Hizentra] approved.”

Matthew Jacobsen was also covered for Cuvitru on a UHC insurance plan, but his father changed jobs in the fall of 2023. Matthew remained on their previous plan under COBRA to smooth the transition and allow time for his prior authorization for Cuvitru to be processed. When Matthew transitioned to his father’s new UHC plan on December 1, 2023, his parents weren’t aware that Cuvitru would not be covered. 

UHC denied Matthew’s prior authorization, stating that Cuvitru was not medically necessary to treat his XLA. The wording in his denial caused weeks of confusion, because, of course, Ig is medically necessary for the treatment of XLA. Matthew’s doctor submitted a second prior authorization for Cuvitru citing medical necessity for XLA, which was again denied.

“It took from December to February in order for him to get his first dose because of all of the insurance issues,” Jacobsen said. “So in the meantime, we ended up having to pay over $1000 out of pocket to get a dose to bridge him.”

The aftermath of non-medical switching of Ig

Matthew was eventually approved to start Hyqvia, which is a 10%, facilitated SCIG product. Whereas he used to infuse 25 milliliters of Cuvitru, Hyqvia requires him to infuse ten times as much fluid. As a lanky 13-year-old with little subcutaneous fat, that’s a lot of fluid in very little space. 

“It’s not apples to apples, it’s completely different meds,” Jacobsen said of the switch.

In addition, the enzyme that facilitates absorption of the Ig requires a ramp-up period, and the medication has to be administered with nurse support for at least the first eight infusions. 

Jacobsen said that her son is uncharacteristically tired after his Hyqvia infusions and has local site soreness for a couple of days. Though the infusion only takes an hour and a half, “I didn't bring him back to school because he's just like, ‘Mom, I don't feel great.’,” she said of his most recent infusion. At the time of publication, Matthew is still not on the full recommended infusion dose and has had to miss school for every infusion. 

Gabriel’s side effects on her new medication, Hizentra, have been even worse. 

“During the infusion, I feel burning and really bad itching at the sites [and] because of the inflammation, my medicine doesn't get absorbed all the way,” said Gabriel describing her recent infusions. “I will feel pain for the following day or two, to the point where I can't sleep on my sides.” 

A pharmacist at Optum, her specialty pharmacy under UHC, attributed these symptoms to an allergic reaction. That reaction is also leading to leakage and, potentially, sub-therapeutic Ig levels, placing Gabriel at risk for infection.

“It just hasn't been good and I told my doctor about it and she agreed, ‘That sounds like an allergic reaction, we need to get you off.’” Gabriel said the pharmacist at Optum even worked directly with her doctor to supplement the appeal to get Gabriel back on Cuvitru. That appeal has been in process for months and Gabriel does not know when UHC will make a decision. 

After consultation with her doctor and the specialty pharmacist, Gabriel is switching yet again, this time to the only other 20% Ig covered by UHC, Xembify. However, the pharmacist was not optimistic that the switch will alleviate her side effects because Xembify contains one of the inactive ingredients in Hizentra that may be causing Gabriel’s reactions. If she experiences an allergic reaction on Xembify, her doctor will dutifully add documentation to her Cuvitru appeal. But with that appeal still pending and a lack of clear communication from UHC, it is unclear what her options will be.

Meanwhile, Jacobsen said she was told that her son would have to “fail all [covered Ig medications] before [UHC] would consider going back to the Cuvitru and some of them were back to IVIG options, meaning him having to go back to the hospital and miss school, as an eighth grader.” 

Patient pushback forces UHC to reinstate Cuvitru coverage

Research shows exactly what Gabriel and Jacobsen’s experiences demonstrate—that for medically stable patients, non-medical switching has negative and costly consequences, not just for patients, but for the larger medical system.

In UHC’s response to IDF’s email seeking comment for this story, UHC revealed that they will be reintroducing coverage for Cuvitru in July, but that the other three medications will remain off-plan.

“When we presented the clinical comparability of all of the therapies at our meeting with the Immune Deficiency Foundation on November 11, 2023, we understood Dr. Fuleihan to have agreed that there wasn’t a clinically meaningful difference between them. When medications in a class of drugs cost significantly more than their equivalents without providing documented additional clinical benefit—like Asceniv, Cutaquig, and Panzyga—we sometimes exclude them from coverage. We recently made the decision to bring Cuvitru back into coverage effective July 1, 2024.”

IDF Medical Advisory Committee Vice Chair, Dr. Ramsay Fuleihan, sat in on the November meeting with UHC to explain clinically why coverage of all Ig products is essential for patients. In response to UHC’s statement, Fuleihan said, “It is funny how they take things out of context. We did agree that all products served the same purpose but [I] wanted to maximize choice, as patients tolerate products differently.” 

Lynn Albizo, IDF’s Chief Policy Officer, who was also present at the meeting, said, “I think they missed the point with Dr. Fuleihan. The point is not that they are not clinically comparable. The point is that they are not the same and that different patients have different reactions to ingredients. He made it clear that some patients can tolerate some formulations and not others. That is why doctors need to have choices and patients who have a history of a drug working for them without side effects should not have to keep trying different treatments when they know there is one that they respond well to.”

As a dentist, Jacobsen said she gets that insurance is a business, but she is not convinced that keeping her son off Cuvitru actually saved UHC any money. 

“I've got a new infusion pump that is more expensive than the syringe pump I used to have. I have so many more supplies that we have to deal with and a whole different way of infusing, including having a nurse come here 8-12 times to teach us how to do it,” she said. “I would love to know what their reasoning is and, if it's for financial gain, that's absolutely ridiculous.”

While Jacobsen is happy that Cuvitru will be covered again, the reversal has opened up even more questions for her. 

“I would like more detail about their pharmaceutical board and how many clinical immunologists ‘sit’ on it. Also, how many external practicing physicians constitute their committee, and what are their specific specialties?” she asked. “This just got me more fired up because so many people have been affected by their hasty decision to remove Cuvitru. Also, I wonder why they decided to add it back on if there was no ‘clinically meaningful difference,’” she said. And finally, “Why are they waiting until July??”

Said Gabriel, “I'm thrilled that they are bringing Cuvitru back! However, I'm confused as to why they're waiting so long to bring it back when they know people are suffering. I also don't understand why they don't bring all of the products back, at least as non-preferred drugs, since there's a need for patients to have options. There's a massive difference between listing a medication as a non-preferred drug and having the ability to show why someone needs it [with an appeal] and as something ‘not medically necessary,’ which allows for no wiggle room.”