Florian Rieder, MD, on Biosimilars for Today and Tomorrow

Biosimilars have demonstrated through several clinical trials that they provide the same efficacy and safety as the reference products, Florian Rieder, MD, told the attendees at the Advances in Inflammatory Bowel Diseases virtual regional meeting March 5.

Dr Rieder is vice chair of the department of gastroenterology, hepatology and nutrition at Cleveland Clinic.

“Biosimilars are already approved in the US and they are here to stay,” he said, noting that both adalimumab and infliximab have several approved biosimilars. He explained that biosimilars can have minor differences in clinically inactive components; they are highly similar but not identical. Comparability assessments consider quality, pharmacokinetics, pharmacodynamics, efficacy, and safety between biosimilar and reference product

These therapeutics are approved by the US Food and Drug Administration (FDA) via an abbreviated pathway which relies on similarity to reference product, Dr Rieder explained. They must show comparable structure and function, immunogenicity, animal toxicity, pharmacokinetics, and pharmacodynamics, along with clinical efficacy and safety for any indication—not for all indications for which the originator product is approved.

“Approved biosimilars can be extrapolated to any indication the reference product is approved for after 1 comparative randomized clinical trial demonstrating noninferiority for any indication,” Dr Rieder explained. For example, a randomized clinical trial of a biosimilar for treatment of rheumatoid arthritis (RA) can be extrapolated to its use in treating inflammatory bowel disease (IBD).

The PLANETAS trial in RA compared the biosimilar CT-P13 to the originator, infliximab, and found equivalent efficacy at week 30 and no differences in adverse events, as well as comparable pharmacokinetics and immunogenicity. “These two are in fact comparable,” Dr Rieder stated.

Another trial of CPT-13 among patients with moderate to severe Crohn disease (CD) showed no differences in the primary endpoint of clinical response and remission at week 6 as defined by the Crohn Disease Activity Index and at week 30. No differences were found in fecal calprotectin, adverse events, drug levels, or antidrug antibodies among patients on the biosimilar and the originator.

In the case of patients in stable remission on an originator, should clinicians and patients worry that switching to a biosimilar will cause the patient to relapse? “We don’t need to be afraid,” Dr Rieder said, noting the results of the NOR-SWITCH trial. In this 52-week, randomized, double-blind, noninferiority study, in patients with IBD were switched from originator to biosimilar and back again with no interruption in remission. The results of the trial and the long-term extension demonstrated no differences. “An explorative IBD subgroup analysis also showed noninferiority and no change in trough levels, antidrug antibodies, disease activity scores, fecal calprotectin, C-reactive protein, or adverse events.”

The VOLTAIRE-CD randomized controlled trial of originator adalimumab to adalimumab-adbm stratified patients by prior exposure to infliximab and by Simple Endoscopic Score for Crohn Disease (SES-CD). The primary endpoint was the Crohn Disease Activity Index at week 4. In this phase 3, double-blind, multicenter, noninferiority study, again there were no differences found between the biosimilar and originator, nor in a safety follow-up during weeks 46 to 56.

Dr Rieder highlighted that FDA approved adalimumab-adbm as “interchangeable,” which means it can be substituted for the originator at the pharmacy level, without knowledge of the prescriber. This is first time a biosimilar has been given the interchangeable designation. To date, 45 states and Puerto Rico have passed laws to allow pharmacy-level substitution.

When positioning biosimilars in IBD treatment paradigms, Dr Rieder explained, physicians should be aware that patients who developed clinically significant antibodies or showed primary nonresponse to the reference product, the biosimilar should not be used. The close similarity between these therapies virtually ensures that patients will develop antibodies or fail to respond to the biosimilar, as well.

“We can use a biosimilar after drug holiday in a rechallenge,” he stated, “and as with the reference product, combination therapy with thiopurine or methotrexate and a biosimilar is still recommended in the right clinical context.”

Patients often hesitate about using a biosimilar, Dr Rieder pointed out. “The majority have never heard of biosimilars,” and may have concerns about safety and efficacy. This can lead to what is called the “nocebo effect” in 10-15% of patients, in which the expectation that the biosimilar will not work as well leads to lack of response or adverse events.

Dr Rieder suggested that good provider-patient communication; multidisciplinary management by physicians, nurses, pharmacists, and others on the care team to educate patients; detecting nocebo via tools that evaluate patient expectations and detect subjects at risk; and social observational learning, take into account individual patient characteristics to facilitate education and shared decision making, can help to counteract the nocebo effect.

“There are excellent resources for patient education from the American Gastroenterological Association, the Crohn’s & Colitis Foundation, and FDA, that are written specifically for patients to answer their questions and allay their concerns,” Dr Rieder said.

—Rebecca Mashaw

 

For more content from the Advances in Inflammatory Bowel Disease 2022 Regional Meetings, visit our Meeting Newsroom.

Reference:
Rieder, F. Biosimilars for today and tomorrow. Presented at: Advances in Inflammatory Bowel Diseases. March 5, 2022. Virtual.