K-Cast Written Summary. Key Patient Considerations for Use of Intravenous and Subcutaneous Therapies

To view this K-Cast video series, click here.

Biologics have transformed the treatment of autoimmune diseases such as rheumatoid arthritis, psoriasis, Crohn’s disease and ulcerative colitis. Jill Zouzoulas, M.D., a rheumatologist at Tryon Medical Partners in Charlotte, North Carolina, and Jennifer Seminerio, M.D., director of inflammatory bowel disease at University of Southern Florida Health in Tampa, Florida, discussed biologics and their intravenous and subcutaneous delivery methods in Managed Healthcare Executive’s K-Cast video series.

Advent of biologics

Enbrel (etanercept), the first biologic used to treat rheumatoid arthritis, was approved by the FDA in 1998. A tumor necrosis factor inhibitor, Enbrel was a leap forward in treating the inflammation of rheumatoid arthritis with more precision. “Part of what attracted me to rheumatology is that we finally had targeted therapies,” noted Zouzoulas. The outcomes for the biologics were significantly better than they were for the other treatment drugs, she said.

Seminerio said biologics were already being used as she was undergoing training. “It’s been very exciting and interesting that our knowledge on how to use them correctly has only grown.” She said her experience with biologics has been very positive. “I think that it’s been an opportunity for us to get a disease state for which we don’t have a cure under control. What I mean by that is we don’t have a way to make ulcerative colitis or Crohn’s disease end — a cure — but we can put it into remission.”

Infusions vs. subcutaneous injections

Biologics can be delivered intravenously or as subcutaneous injections. Zouzoulas described the increasing availability of subcutaneous biologics as being “fantastic” for patients who are working. A lack of familiarity with self-injection and worry about pain can sometimes stir up reluctance. “In actuality,” said Zouzoulas, “once you walk the patient through that, once you train them how to use it and build the confidence, that quickly goes away and patients are just very happy that they don’t need to come in and take time away from their regular lives.” The risk of reaction is very low, Zouzoulas said, as is the chance of administering the wrong dose.

Seminerio said she has also worked to assuage patient fears of subcutaneous injection and that self-administration empowers patients, she said. “It allows them to feel like they’re still treating their disease, but they don’t have to give up key points in their life.” Seminerio said she can still recall her excitement for her patients when Stelara (ustekinumab), the first subcutaneous biologic for Crohn’s disease and ulcerative colitis, became available.

There are, though, advantages to IV infusions, noted Zouzoulas. Having patients come in regularly helps physicians and other clinicians monitor them and coordinate their care. The regularity of the visits helps patients build connections with staff and other patients, Zouzoulas said. “The nurses, especially in the infusion suite, come to know them over time, and they feel very much like they’re almost part of a community. And they tend to talk to each other and people are oftentimes scheduled on the same day so it almost in some ways is a support group for them.”

Body weight is a factor that Zouzoulas also considers. Many studies have shown that IV infusions are preferable for patients who weigh more than 100 kilograms [about 220 pounds], she said.

Seminerio said that IV formulations may be advantageous for patients for whom adherence is an issue. Clinicians and their staff can keep track of which patients come to an infusion center and receive treatment; self-administration of subcutaneous formulation is inherently more difficult to monitor. But Seminerio also stressedthe importance of patient choice.

Cost and billing considerations

Commercial insurers cover IV and subcutaneous therapies fairly similarly, according to Zouzoulas. Patients with traditional Medicare and Medigap coverage will have their biologic medication almost completely covered after meeting a deductible, she said. Those in a Medicare Advantage plan get 80% of the cost of an IV biologic covered, which Zouzoulas said may seem generous but “the remaining 20% is also a big number” given the price of the biologics.

To view this K-Cast video series, click here.

Seminerio noted that the medical-pharmacy benefit divides in U.S. healthcare coverage: IV drugs are paid through the medical benefit whereas subcutaneous ones are paid through the pharmacy benefit. For clinicians working with an infusion center, billing through the medical benefit is usually a fairly streamlined process, she said, particularly for well-established drugs. Drugs paid for through the pharmacy benefit can, in contrast, be more problematic because of prior authorization and appeal processes that can take months and requirements that patients be treated with certain drugs before others. “Sometimes you just need to make sure that you’re staying on it,” she said. Specialty pharmacies step in and help with those processes, Seminerio said, although sometimes insurance companies mandate the use of specific specialty pharmacies.

Zouzoulas said staff in her office handle prior authorizations for the IV biologics because her office is buying the drug and administering it to the patient before getting reimbursed. Her office also handles prior authorizations for subcutaneous biologics, but Zouzoulas said that it is often an easy, online experience and that specialty pharmacies help with the process.

Biosimilars

Biosimilars came into use very slowly in rheumatology, Zouzoulas said, starting with biosimilars to Remicade and Rituxan (rituximab). Over time, insurers have changed their formularies so patients often need to try one or two biosimilars before they will cover the brand-name product, said Zouzoulas. “Oftentimes patients will ask me how I pick a biosimilar. And I say, ‘I don’t. Your insurance does.’ ” Because biosimilars to IV biologics have driven down reimbursement rates, some doctors have stopped giving those drugs and have those patients go to freestanding corporate infusion suites or hospital infusion suites. In Zouzoulas’ view, biosimilars have benefited the distribution companies and pharmacy benefit managers while the out-of-pocket costs for patients have stayed the same.

Seminerio had a more positive outlook on biosimilars. She said the NOR-SWITCH study showed that patients can be safely switched from a brand-name drug to a biosimilar. If an insurer requires a switch, she says she stays matter-of-fact. “The way that I have that conversation with [the patient] is, ‘Listen, if we don’t do this, we’re going to end up with no medication. Or you’re going to end up paying a cost that may not be feasible for you. So let’s do it.’”

The future

Zouzoulas said biologics are shifting away from IV formulations toward subcutaneous and oral ones. Drugmakers are less inclined to make an IV formulation of a biologic if they can make a subcutaneous one and are less likely to make both, she said.

Seminerio sees problems coming from the growing number of drugs. “With more drugs, with more mechanisms of action, there becomes a greater gap in our ability to know which one to use when you’re not specifically practicing [IBD] medicine.” She said it is up to IBD specialists to educate physicians coming into the field and practitioners in the community. Seminerio said she also wants to see more head-to-head trials such as the VARSITY trial, which compared Entyvio (an IV drug) to Humira (a subcutaneous one) in patients with moderate-to-severe ulcerative colitis. Entyvio proved to be more efficacious. “I think it allowed people to see that sometimes it isn’t a matter of just IV versus [subcutaneous]. It’s the drug itself and which one is going to work better.”