乌鸦传媒

On October 18, 2021, 乌鸦传媒 reported on the approval of Cyltezo, the first interchangeable biosimilar approval for adalimumab (Humira), covering a range of indications, including Crohn's disease (CD). Here we provide a follow up to this story and further developments in CD since this initial report.

The FDA made Cyltezo (adalimumab-adbm) just the second biosimilar product to gain the coveted interchangeable status, and the first biosimilar to Humira (adalimumab) with this designation.

"The whole novelty is, it is the first biosimilar that has been designated as both 'biosimilar' and 'interchangeable,' meaning non-medical switches are less of a concern for loss of response, adverse effects, or other issues," Dana Lukin, MD, PhD, of Weill Cornell Medicine in New York City, told 乌鸦传媒. "Humira [developer AbbVie] has any of the biosimilars from for quite some time despite the FDA approvals."

Cyltezo was but will not be commercially available in the U.S. until 2023.

In adults, for the tumor necrosis factor (TNF)-alpha inhibitor covers indications in moderate-to-severe CD along with multiple other chronic inflammatory diseases -- ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, and ankylosing spondylitis. In the pediatric setting, the biosimilar is indicated for moderate-to-severe polyarticular juvenile idiopathic arthritis in those ages 2 years and older, and for CD in kids ages 6 years and older.

"I believe that biosimilars are equal to the originators and can be used for patients," noted Paul Lebovitz, MD, of Allegheny Health Network in Pittsburgh. "In many ways, each batch of originator is a little different than the last since they're from living organisms, so already is in some ways a biosimilar."

"However, I would prefer not to change in the middle of induction of a drug if able," Lebovitz added.

The "interchangeable" status approval for Cyltezo was based on a demonstration of equivalency in the randomized phase III , which involved multiple Cyltezo to Humira switches versus continuously administered Humira in patients with plaque psoriasis.

Other Developments in CD

"For patients with moderate or severe Crohn's, it is most appropriate to use induction therapy with a tumor necrosis factor alpha antagonist -- ustekinumab [Stelara], or vedolizumab [Entyvio]," Lukin explained. During induction, a limited course of corticosteroids may benefit inflammation and symptoms, but "should be tapered as quickly as possible," he said.

For patients with severe CD in a post-operative state, or with a perianal fistula, the TNF antagonist class has "provided the highest efficacy, and may be preferred for those with joint pain related to their Crohn's disease," Lukin added.

At the 2021 American College of Gastroenterology (ACG) meeting, results from the phase III FORTIFY study were presented. In that trial, two different subcutaneous maintenance doses of risankizumab (Skyrizi) sustained clinical remission and endoscopic responses for moderate to severe CD previously treated with the anti-interleukin (IL)-23 antibody.

Investigator Marla Dubinsky, MD, of the Icahn School of Medicine at Mount Sinai in New York City, reported that 55.4% and 52.2% of patients receiving subcutaneous risankizumab doses of 360 mg or 180 mg, respectively, were in clinical remission at week 52 versus 40.9% of those assigned placebo (P<0.01 for both). Endoscopic response rates doubled with risankizumab by this point as well, at 47.1% and 46.5% for the two respective doses versus 22% with placebo (P<0.001 for both).

Recently reported long-term results from the TAILORIX trial showed that achieving a sustained clinical remission off steroids with complete endoscopic remission in early CD was not tied to less disease progression, with similar progression-free survival at 1, 3, and 5 years for CD patients meeting the remission endpoint and those that did not.

Investigator David Laharie, MD, of the Hôpital Haut-Lévêque in Bordeaux, France, said his group supported early use of aggressive treatment to modify the historic course of CD, and a "flexible approach to the target-to-treat concept" in routine practice. "The cutoff for defining endoscopic remission in CD remains unknown," Laharie said. "We need prospective trials to better define therapeutic goals that actually change the natural course of the disease and prevent complications."

Lukin added that "there is a significant need for novel, safe, and effective therapies for mild-to-moderate Crohn's disease, those with fibrostenotic complications (stricture), perianal and internal fistulizing Crohn's disease, and for microbiota-based therapies."

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