Patients with inflammatory bowel disease (IBD) will soon have access to new biosimilars to infliximab, adalimumab, and other monoclonal antibodies, experts wrote in an American Gastroenterological Association clinical practice update.
“It is anticipated that biosimilars for IBD are here to stay,” wrote Laura E. Raffals, MD, of the Mayo Clinic in Rochester, Minn., and her associates in Clinical Gastroenterology and Hepatology. “Provided that the regulatory pathway remains rigorous and postmarketing surveillance is performed adequately, clinicians and patients can be reassured that these agents will provide the same well-described effectiveness for moderate to severe Crohn’s disease and ulcerative colitis, without new safety concerns.”
Evidence supports the use of biosimilars in IBD, but switching patients in stable remission on infliximab (Remicade) to a biosimilar, namely infliximab-dyyb (Inflectra), should remain a case-by-case choice, according to an AGA clinical practice update. Pending more safety data, the update’s authors recommended against nonmedical switches during pregnancy and urge special attention when considering whether to switch children.
Biologics have revolutionized IBD treatment, but at a steep price. As patents expire, companies have developed biosimilar agents that aim to conserve safety and efficacy at lower cost. Studies support this idea, although whether initiating or switching to biosimilars will save patients (versus hospitals or payers) money “remains to be seen,” the practice update states.
The FDA approval process for biosimilars is more rigorous than that for generics, but it skips the multiple phases of clinical trials required to approve reference biologics. Instead, the FDA requires robust evidence that the biosimilar has comparable structure, function, immunogenicity, animal toxicity, pharmacokinetics and pharmacodynamics, and clinical safety and efficacy in humans. Under U.S. law, a biosimilar cannot be FDA approved if its clinically active components differ from the reference product or it shows clinically meaningful differences in safety, potency, or purity.
So far, five biosimilars have been approved by the FDA for use in IBD, although not all are on the market yet: infliximab-dyyb (Inflectra), adalimumab-atta (Amjevita), infliximab-abda (Renflexis), adalimumab-adbm (Cyltezo), and infliximab-qbtx (Ixifi). Most postmarketing studies of their use involved patients on stable doses of Remicade who switched to biosimilar infliximab-dyyb (Inflectra).
The best known of these studies is the double-blind, randomized NOR-SWITCH trial, in which patients with Crohn’s disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, or chronic plaque psoriasis on Remicade either continued it or switched to biosimilar infliximab-dyyb (Inflectra). At week 52, both safety and the likelihood of worsening disease activity were similar regardless of treatment randomization. The study was not powered to assess subgroup outcomes in Crohn’s disease or ulcerative colitis, the practice update notes.
More recently, the results of the 16-week SECURE trial also indicated that switching to infliximab-dyyb (Inflectra) was safe and well tolerated by patients with remitted IBD. However, the FDA has not yet designated any biosimilar as “interchangeable” with an approved biologic confirmed safe in multiple switches, the practice update notes. As a result, state laws prohibit patients from being switched to a biosimilar without notification. Both the NOR-SWITCH and SECURE trials were done in Europe.
Clinicians also must understand that antidrug antibodies to originator and biosimilar infliximab cross-react with each other, the experts emphasized. Switching patients with antibodies to Remicade or a biosimilar to the other product therefore risks an immediate hypersensitivity reaction, including life-threatening anaphylaxis.
The authors disclosed no external funding sources. One author disclosed ties to AbbVie, Janssen, Pfizer, Merck, Samsung Bioepis, and Amgen. The rest reported having no conflicts of interest.
SOURCE: Raffals LA et al. Clin Gastroenterol Hepatol. 2018 Sep 6. doi: 10.1016/j.cgh.2018.08.064.