Biosimilar-to-Biosimilar Switches Deemed Safe, Effective Biosimilar-to-Biosimilar Switches Deemed Safe, Effective

Switching from one biosimilar medication to another is safe and effective, a new systematic review indicates, even though this clinical practice is not governed by current health authority regulations or guidance.

“No reduction in effectiveness or increase in adverse events was detected in biosimilar-to-biosimilar switching studies conducted to date,” the review’s authors note in their study, published online July 26 in BioDrugs.

“The possibility of multiple switches between biosimilars of the same reference biologic is already a reality, and these types of switches are expected to become more common in the future. …although it is not covered by current health authority regulations or guidance,” add the authors, led by Hillel P. Cohen, PhD, executive director of scientific affairs at Sandoz, a division of Novartis.

The researchers searched electronic databases through December 2021 and found 23 observational studies that met their search criteria, of which 13 were published in peer-reviewed journals; the remainder appeared in abstract form. The studies totaled 3657 patients. The researchers did not identify any randomized clinical trials.

“The studies were heterogeneous in size, design, and endpoints, providing data on safety, effectiveness, immunogenicity, pharmacokinetics, patient retention, patient and physician perceptions, and drug-use patterns,” the authors write.

The authors found that the majority of studies evaluated switches between biosimilars of infliximab, but they also identified switches between biosimilars of adalimumab, etanercept, and rituximab.

“Some health care providers are hesitant to switch patients from one biosimilar to another biosimilar because of a perceived lack of clinical data on such switches,” Cohen told Medscape Medical News.

The review’s findings — that there were no clinically relevant differences when switching patients from one biosimilar to another — are consistent with the science, Cohen said. “Physicians should have confidence that the data demonstrate that safety and effectiveness are not impacted if patients switch from one biosimilar to another biosimilar of the same reference biologic,” he said.

Currently, the published data include biosimilars to only four reference biologics. “However, I anticipate additional biosimilar-to-biosimilar switching data will become available in the future,” Cohen said. “In fact, several new studies have been published in recent months, after the cut-off date for inclusion in our systematic review.”

Switching Common in Rheumatology, Dermatology, and Gastroenterology

Biosimilar-to-biosimilar switching was observed most commonly in rheumatology practice, but also was seen in the specialties of dermatology and gastroenterology.

Jeffrey Weinberg, MD, clinical professor of dermatology, Icahn School of Medicine at Mount Sinai, New York City, told Medscape Medical News that the study is among the best to date showing that switching biosimilars does not compromise efficacy or safety. 

“I would hypothesize that the interchangeability would apply to psoriasis patients,” Weinberg said. However, “over the next few years, we will have an increasing number of biosimilars for an increasing number of different molecules. We will need to be vigilant to observe if similar behavior is observed with the biosimilars yet to come.”

Keith Choate, MD, PhD, professor of dermatology, pathology, and genetics, and associate dean for physician-scientist development at Yale School of Medicine, New Haven, Connecticut, said that biosimilars have comparable efficacy to the branded medication they replace. “If response is lost to an individual agent, we would not typically then switch to a biosimilar, but would favor another class of therapy or a distinct therapeutic which targets the same pathway,” Choate said.

When physicians prescribe a biosimilar for rheumatoid arthritis or psoriatic arthritis, in nine out 10 people, “it’s going to work as well, and it’s not going to cause any more side effects,” said Stanford Shoor, MD, clinical professor of medicine and rheumatology, Stanford School of Medicine, California.

The systematic review, even within its limitations, reinforces confidence in the antitumor necrosis factor biosimilars, said Jean-Frederic Colombel, MD, codirector of the Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, New York City, and professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai.

“Still, studies with longer follow-up are needed,” Colombel said, adding that the remaining questions relate to the efficacy and safety of switching multiple times, which will likely occur in the near future. There will be a “need to provide information to the patient regarding what originator or biosimilar(s) he has been exposed to during the course of his disease.”

Switching will increasingly become the norm, said Miguel Regueiro, MD, chair of the Digestive Disease & Surgery Institute, Cleveland Clinic, Ohio. In his clinical practice, he has the most experience with Crohn’s disease and ulcerative colitis, and biosimilar-to-biosimilar infliximab switches. “Unless there are data that emerge, I have no concerns with this.” 

He added that it’s an “interesting study that affirms my findings in clinical practice — that one can switch from a biosimilar to biosimilar (of the same reference product).”

The review’s results also make sense from an economic standpoint, said Rajat Bhatt, MD, owner of Prime Rheumatology in Richmond, Texas, and an adjunct faculty member at Caribbean Medical University, Willemstad, Curaçao. “Switching to biosimilars will result in cost savings for the health care system.” Patients on certain insurances also will save by switching to a biosimilar with a lower copay.

However, the review is limited by a relatively small number of studies that have provided primary data on this topic, and most of these were switching from infliximab to a biosimilar for inflammatory bowel disease, said Alfred Kim, MD, PhD, an adult rheumatologist at Barnes-Jewish Hospital and assistant professor of medicine at Washington University School of Medicine in St. Louis.

As with any meta-analysis evaluating a small number of studies, “broad applicability to all conditions and reference/biosimilar pair can only be assumed. Also, many of the studies used for this meta-analysis are observational, which can introduce a variety of biases that can be difficult to adjust for,” Kim said. “Nevertheless, these analyses are an important first step in validating the [Food and Drug Administration’s] approach to evaluating biosimilars, as the clinical outcomes are consistent between different biosimilars.”

This systematic review is not enough to prove that all patients will do fine when switching from one biosimilar to another, said Florence Aslinia, MD, a gastroenterologist at the University of Kansas Health System in Kansas City. It’s possible that some patients may not do as well, she said, noting that in one study of patients with inflammatory bowel disease, 10% of patients on a biosimilar infliximab needed to switch back to the originator infliximab (Remicade, Janssen) because of side effects attributed to the biosimilar. The same thing may or may not happen with biosimilar-to-biosimilar switching, and it requires further study, she said.

The authors did not receive any funding for writing this review.

Cohen is an employee of Sandoz, a division of Novartis. He may own stock in Novartis. Sandoz manufactures and markets multiple biosimilars worldwide, including several discussed in this publication. Two coauthors are also employees of Sandoz. The other three coauthors report having financial relationships with many pharmaceutical companies, including Sandoz and/or Novartis. Colombel reports financial relationships with many pharmaceutical companies, including Novartis and other manufacturers of biosimilars. Regueiro reports financial relationships with many pharmaceutical companies, including some manufacturers of biosimilars. Weinberg reports financial relationships with Celgene, AbbVie, Eli Lilly, and Novartis. Kim reports financial relationships with GlaxoSmithKline, Pfizer, and AstraZeneca. Aslinia, Shoor, Choate, and Bhatt report no relevant financial relationships.

BioDrugs. Published online July 26, 2022. Full text.

Susan Kreimer is a New York-based freelance health journalist.

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