A Blueprint for Successful Infliximab Biosimilar Switching

Payers have not been quick to add biosimilar infliximab to their drug coverage. Yet, biosimilar switching is the objective for most health plans and insurers who are thinking about long-term savings. Even if they do not exclude the reference product Remicade® from coverage, some health plans, like Kaiser, have been moving forward in this effort.

At the Academy of Managed Care Pharmacy’s Nexus 2018 meeting in Orlando this week, two clinical pharmacy specialists from Kaiser Foundation Health Plan of the Northwest described what may be a best practice in converting patients to biosimilar Inflectra®.

RELEVANCE OF BIOSIMILAR SWITCHING AT THE PLAN LEVEL

Kayla Hubrich, PharmD, emphasized the importance of patient education, and patients’ reliance on Google for research. She said, “When patients will turn to Google and type in ‘Should I switch to an infliximab biosimilar?’ the first search result they see is an ad for ‘Finely Tuned,’ a Janssen website.” This, of course, discourages the use of biosimilars.

At Kaiser Foundation Health Plans, coverage decisions are made at a national level for its 12.5 million members and implemented at the regional plan level, according to Lynsey Smith, PharmD. The health plan made Zarxio® its preferred filgrastim product in 2016, and registered 96% of all filgrastim dispensings in self-injected settings, and 100% of all clinical administrations for this biosimilar.

Biosimilar switching
Source: Kaiser Foundation Health Plan

Obtaining that level of use means that not only treatment-naive patients were using Inflectra, but also those using Remicade in the past. Dr. Smith outlined the key steps in this conversion, starting with the providers. “For new starts,” said Dr. Smith, “the tactic was just to have the doctor choose the biosimilar” using tools incorporated into the electronic health record that encouraged them to order the preferred product. Concerning those patients needing to be converted from the reference product, Kaiser asked the prescriber to sign a ‘Therapeutic Equivalency Protocol’ agreement, which authorized the plan to make the switch. The biosimilar switching agreement was voluntary, and virtually all the rheumatologists, dermatologists, and gastroenterologists signed. “One GI out of 20 declined to authorize the switch in patients already receiving Remicade,” she said.

Kaiser emphasized patient notification and education. A letter, signed in their doctor’s name, was sent to each patient at least 2 weeks before the conversion date, explained Dr. Smith. Clinical Pharmacy Services was enlisted to answer patients’ questions via phone and E-mail. Patients were also given informational handouts about the biosimilar switching program at their infusion center.

“During this process, the clinical pharmacists received 30 to 40 calls,” she said. “The patients’ main concerns were whether the product was going to work as well as their old drug and whether they would receive the same copay assistance as before.” Active patient outreach was not conducted after the switch was instituted. Any patients reporting issues or concerns were triaged through Clinical Pharmacy Services.

Dr. Hubrich added that infusion center pharmacists reviewed all patients scheduled for infusions one week ahead of their appointment. The infusion center confirmed that the provider signed a TEP document, that patients were sent the notification letter, and that the infliximab order changed to Inflectra. Kaiser also developed a nurses’ protocol for the biosimilar switch and worked to educate practice staff about the program.

 

INFLIXIMAB SWITCHING PROGRAM RESULTS

The conversation program began on May 1, 2017, with dermatologists and rheumatologists, focusing on patients who were getting their first infliximab treatment. Dr. Hubrich stated that notification letters were sent to 158 patients. Three weeks later, current patients began to be switched from Remicade to Inflectra. The GI conversion began on May 11, 2017 with treatment-naïve patients, and letters were sent to 188 adult patients (as Inflectra did not have the pediatric ulcerative colitis indication). Active therapeutic switching began in September. “The one GI who declined to sign the TEP agreement joined in 2018,” said Dr. Hubrich. This is likely because of the experience of this doctor’s peers.

A total of 22 patients (6.4%) across specialties reported adverse events, with nine being changed back to reference product (2.6%), five changed to a different medication class, four resulted in a dosage increase, one patient decided to discontinue therapy, and three continuing biosimilar infliximab treatment without any change. They did find that 12.8% of patients experienced some “nocebo” effects, despite the fact that “no statistically significant changes in effectiveness and safety were observed after a medican of four infusions in 9 months of study.”

Dr. Smith asserted that communication was critical to the success of the program, with patients and providers. The provider’s agreement to sign the TEP document was a necessary step, and was accepted by all Kaiser’s specialist providers.

It must be emphasized that Kaiser has a different magnitude of leverage over its physicians than a network plan like Aetna or CIGNA. Yet a biosimilar switching program like this could be a blueprint for other integrated health plans to move forward if they desire to move patients quickly and efficiently to biosimilar therapy.

Interchangeability: Another Challenging Perspective

Although the FDA has offered a pathway for the interchangeable designation, a recent presentation at the AMCP Nexus meeting shone a new light on some fairly important challenges posed by the interchangeable designation.

Edward Li, PharmD, MPH, Professor of Pharmacy, University of New England, Portland, Maine, raised the Web image 3well-trod issue of manufacturing drift—that over time, the reference product in particular is often subject to slight changes in structure that may be due to manufacturing changes, or other factors. This is an extremely important concept in biosimilars, as it highlights that these biologics can never be exact copies of the biologic drug. In fact, the originator biologic produced today cannot be expected to be exactly the same as the medication that was first approved 15 years ago. Although the structure may have changed subtly in these complex molecules, the clinical effects and outcomes have not materially changed. With interchangeability, Dr. Li said, “There should be no clinically meaningful differences,” in terms of safety, purity, and potency.

Once the FDA assigns the interchangeability designation to a prospective biosimilar or one that has already been marketed (and subsequent studies have provided FDA with the data to conclude that it is interchangeable with the originator), payers expect to be able to freely substitute this biosimilar for the originator at the point of dispensing—an expected boon to health plans and insurers, as well as the biosimilar maker.

However, what of the interchangeable biosimilar in the future? If manufacturing drift continues to occur over the course of time, the variation in the biosimilar and originator product will have introduced new subtle changes compared with that previously used in the approval process. “Differences may accumulate over time,” said Dr. Li, and hypothetically, these can lead to differences in safety and efficacy.” Does the biosimilar manufacturer need to prove interchangeability all over again, five years later? Is there a possibility that the biosimilar can be reduced back to the ranks of ordinary biosimilars?

These are important questions. Only after we have a biosimilar  designated as interchangeable will we be able to broach this question. However, it does perhaps give the reference drug maker a line of defense in sparing loss of marketshare.