Damian McNamara

December 11, 2015

ORLANDO — For patients with ulcerative colitis and Crohn's disease, a big change in treatment is coming, and gastroenterologists in the United States are scrambling to get ready. They have to learn how to talk to patients about the potential risks and benefits of new agents that are "biosimilar" to biologic therapies.

"For many in this room, this is a topic you may know very little about," David Rubin, MD, from the University of Chicago Medical Center, said during a discussion on the topic here at the Crohn's and Colitis Foundation of America Advances in Inflammatory Bowel Diseases Conference.

Biosimilars are coming, he said. "They're already in Europe and Asia, and you should know about them because they will influence our practice."

"This is an enormous deal," said Miguel Regueiro, MD, from the University of Pittsburgh. "Whether we like it or not, this is what we are going to be faced with in the future."

International experience has shown that biosimilars could cost up to 30% less than many biologics on the market. However, there are potential concerns about the agents related to immunogenicity, interchangeability, and "nonmedical switching."

Potential Immunogenicity a "Major Issue"

Biosimilars carry potential for immunogenicity or cross-reactivity if you stay within a class, Dr Rubin said. "If you have antibodies to infliximab [Remicade] and you go to an infliximab biosimilar, you're likely to have the same issue as before."

Dr Stephen Hanauer

Immunogenicity is going to be one of the major issues between biosimilars and the originators, predicts Stephen Hanauer, MD, from the Feinberg School of Medicine at Northwestern University in Chicago. Individual genetics determine some aspects of immunogenicity, but most of the determinants remain unknown. More research is needed, he said.

Biosimilars are not generics, Dr Rubin pointed out. "They are highly complex structures, difficult to replicate, and they have much higher immunogenic potential."

Issue of Interchangeability Remains

Biosimilars "are not identical; they are similar to the greatest extent that the new company can probably make them," Dr Hanauer explained. The protein structure can match the biologic, for example, but the sugar component — the glycosylation — varies according to a number of different factors.

Because biologics are made in live animals, even the same biologic agent tends to vary over time, said Brian Feagan, MD, from the Robarts Research Institute at the University of Western Ontario in London, Canada. He referred to this heterogeneity over time as "manufacturing drift." In their defense, he added, "manufacturers will say they have quality control protocols."

To determine what changes, if any, will result when a patient is switched from a biologic to its biosimilar will require 18 months of rigorous study, said Dr Feagan.

Dr Hanauer said he agrees, adding that multiple switches will be needed to rule out any significant differences between agents.

Nonmedical Substitutions

The availability of biologics in the United States will likely raise another issue: insurance company or nonmedical switches from biologics to biosimilars. Historically, many insurers pay for a less-expensive agent when one is available. With nonmedical biosimilar switches, it is not known how a patient's response could change, Dr Rubin explained.

"Nonmedical-switching patients are more likely to have poor control," he said. "We have to be careful when we electively change therapies."

Variations in state law are an additional concern. Even as agents gain federal approval, state laws on biologics vary.

Not Quite Ready for Prime Time

"There's certainly more to learn," said session moderator Corey Siegel, MD, from the Dartmouth–Hitchcock Medical Center in Lebanon, New Hampshire.

"In the end, it's all about what is best for the patient. Our hope is that we can capitalize on the European experience," he told Medscape Medical News.

The availability of biosimilars for the treatment of inflammatory bowel disease could be positive, "assuming we're looking at significant efficacy and decreased cost," Dr Siegel added. "But we're not quite ready to make the leap yet."

Dr Rubin reports relationships with AbbVie, Amgen, Cornerstones Heath, Emmi, Genentech, Janssen, Pfizer, Prometheus, Shire, Takeda, and UCB. Dr Regueiro reports relationships with AbbVie, Janssen, Shire Takeda, and UCB. Dr Hanauer reports relationships with AbbVie, Actavis, Amgen, Arena, Astellas, Boehringer Ingelheim, Bristol-Myers Squibb, Catabasis, Celltrion, Ferrring, Genetech, GlaxoSmithKline, Hospira, Janssen, Lilly, Novartis, Novo Nordisk, Pfizer, Prometheus, Receptos, Saliz, Seres Health, Shire, and Takeda. Dr Feagan reports relationships with AbbVie, Actogenix, Akros, Albireo Pharma, Amgen, AstraZeneca, Avaxia Biologics, Avir, Axcan, Baxter, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring, Roche/Genetech, GiCare Pharma, Gilead, GlaxoSmithKline, Ironwood Pharma, Janssen, Lilly, Lycera, BioTech, Merck, Nektar, Novo Nordisk, Pfizer, Prometheus, Protagonist, Receptos, Salix, Sereno, Shire, Sigmoid Pharam, Takeda, Teva, TiGenix, Tillotts, UCB, Vertex Pharma, Wyeth, Zealand, and Zyngenia. Dr Siegel reports relationships with AbbVie, AHRO, Amgen, Janssen, Lilly, Pfizer, Prometheus, Takeda, Theradiag, and UCB.

Crohn's and Colitis Foundation of America Advances in Inflammatory Bowel Diseases (AIBD) Conference. Presented December 10, 2015.

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