Dec. 6, 2024 — After a 15-year hiatus, one patient was happy to go hiking again. Another said, “I always kept track of where the bathrooms were on my trip to college. Now I don’t have to.” Another no longer has to wear a diaper when performing on stage.
All three have ulcerative colitis, a chronic inflammatory disease of the large intestine (colon), and are on new medications called IL-23 inhibitors.
Perhaps better known to those who pay attention to television commercials as Omvoh, Skyrizi, and Tremfya, the medications work by blocking interleukin 23 (IL-23), an immune system protein that helps protect the body but in excess can lead to inflammation and ulcerative colitis. The medications reduce the symptoms of diarrhea, constipation, and stomach cramping, with a goal of becoming symptom-free, or in remission.
Tauseef Ali, MD, a gastroenterologist in Oklahoma City, OK, shared the case histories of these patients to demonstrate what a difference these new medications are making in treating ulcerative colitis, which affects an estimated 1.5 million people in the U.S. The newer medications aim not only to achieve remission but to heal the bowel.
“The development and approval of these [new] drugs have exploded in the past five years,” said Ali, medical executive director of SSM Health Digestive Care and the Crohn’s and Colitis Center at St. Anthony Hospital, Oklahoma City. Not so long ago, he said, there was a drug approved for ulcerative colitis every five years or so. Development has sped up greatly, with the three new IL-23 inhibitors approved since October 2023.
It’s just the beginning, Ali said. Next up, five drugs approved as biosimilars – drugs that are nearly identical to other, already approved drugs -- for ulcerative colitis treatment are expected in pharmacies in 2025.
The new medications will fill an unmet need, said Ali. While many medications for ulcerative colitis are on the market now, patients’ responses to specific medications tend to decline, so treatments need to be switched, and new approaches are always needed.
About Ulcerative Colitis
More than 1.5 million people in North America have ulcerative colitis, making it the most common type of inflammatory bowel disease (IBD). It affects the inner lining of the colon and rectum, causing damage. Another 1 million have Crohn’s disease, an IBD that can involve inflammation anywhere in the digestive tract.
Symptoms for both IBDs include an urgent need to empty the bowels, frequent blood or mucus in the stool, belly pain, and cramps. While symptoms can be severe, many with ulcerative colitis lead active lives and can have long periods of remission. However, even with the medication advances, about 10% of patients need colon surgery within 10 years of an ulcerative colitis diagnosis.
Newest Options
The new trio of Omvoh (mirikizumab-mrkz), Skyrizi (risankizumab-rzaa), and Tremfya (guselkumab) were developed after scientists found that IL-23 is a major pathway that causes the inflammation characteristic of ulcerative colitis, Ali said.
In clinical trials, all three companies reported that a higher percentage of those on the active drug, compared to placebo, achieved clinical remission, defined as no noticeable symptoms. A higher percentage of those on the drugs also were more likely than those on placebo to have endoscopic remission, defined as no signs of ulcers, bleeding, or inflammation on a colonoscopy or sigmoidoscopy exam.
There are no head-to-head studies to compare the three IL-23 inhibitors, but the trials suggest that their effectiveness is comparable, said Ali.
“Typically, about half of the patients started on this [IL-23] drug class go into remission in the short-medium term,” said Alan Moss, MD, chief scientific officer for the Crohn's & Colitis Foundation, citing research.
In the clinical trials of one IL-23 inhibitor, 23% were in remission at 12 weeks. At one year, more than one-third had endoscopic remission.
Patients are warned that the ability to fight infection can be lower on the drugs. But serious infections or reactions are uncommon, Moss said. Some research has found similar rates of infection among those on the IL-23 inhibitors and those on placebo. With all the available medication options, the goal is to find one that gets a patient into remission and maintains it as long as possible, Moss and other experts agree.
The IL-23 drugs “are typically given as a first dose by infusion, and later doses by an injection under the skin,” said Moss. “The dosing is only once every eight weeks after the first infusion, so this reduces the number of treatments per year a patient needs.”
Coming in 2025: The Biosimilars
Stelara was approved in 2009 for plaque psoriasis and later approved for IBD; it blocks both IL-23 and IL-12, another protein that in excess can cause inflammation and lead to ulcerative colitis. Now, the FDA has approved five biosimilars of Stelara; the most recent is Selarsdi (ustekinumab-aekn). None are in pharmacies yet, Ali said, but will be soon.
Biosimilars are biologic medications that have no clinically meaningful differences from the original product, in the eyes of the FDA. They promise to lower costs.
While the approvals of the biosimilars are recent, Moss offered perspective, noting that after Stelara got approved for psoriasis in 2009, it gained FDA approval for Crohn’s in 2016 and for ulcerative colitis in 2019. “So we have almost eight years of prescribing this type of agent for [IBD] patients in the U.S.”
Other Options, Advances
While the new drugs are getting much attention, and being advertised heavily, other medications approved in the last few years, such as JAK inhibitors (Rinvoq [upadacitinib] and Xeljanz [tofacitinib]), can also produce good results, Ali said.
Combining medications has shown even better results, he added, citing a phase II study that gave participants either Simponi (golimumab) or Tremfya (guselkumab) alone or together. At week 12, 83% of those in the combination group had a clinical response, compared to 61% in the Simponi alone group and 75% of those in the Tremfya alone group.
Costs and Insurance Coverage
The new IL-23 medications’ list prices are high, from more than $10,000 to more than $21,000. But insured patients typically pay much less, even a zero copay.
“For patients with commercial insurance, the biologics agents are all tiered differently based on plan coverage,” Moss said. “Biologic drugs are usually covered, often after patients have already tried first-line drugs. Commercial plans sometimes allow patients to benefit from payment assistance programs supported by the drug company that makes the treatment.”
As for those on Medicare and Medicaid, the rules and coverage vary, he said, “so patients will only know their coverage and copays when it’s prescribed and submitted to their insurance.”
Tailored Treatments
This wider range of medication options can help health care providers tailor the drug to an individual patient’s disease characteristics, Moss said.
“If one type — for example, anti-TNF — doesn’t work, then another class — anti-IL-23 or JAK inhibitors — can be tried,” Moss said.
Anti-TNF, or anti-tumor necrosis factor medications such as Simponi, work by blocking TNF, which can cause inflammation and lead to immune system diseases. JAK inhibitors (such as Xeljanz) work by blocking signaling inside cells to reduce inflammation. This range of options has resulted in fewer patients needing surgery in the last decade, Moss said.
Other good news: “Newer drugs have also shifted from mostly injection treatments to daily pill formats, which give patients more convenient options for their lifestyle,” Moss said. “Newer treatments also promise to not just treat immune cells involved in colitis, but also potentially reverse scare tissue and promote healing of the colon lining.”
Ali has received honoraria from AbbVie and Janssen, serving as a speaker and on advisory boards. Moss is an employee of the Foundation, which obtains financial support from companies that manufacture anti-TNF, anti-integrin, and anti-IL-23 drugs.
