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The past year has seen a multitude of FDA approvals, ranging from IL-23 and JAK inhibitors to biologics and subcutaneous treatment administrations, that have helped redefine what it means to treat IBD.
An estimated 3.1 million adults in the United States are affected by inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn disease (CD).1 Effective therapies used to be few and far between—gastroenterologists had only a handful of treatment options to choose from, and patients had no choice but to settle for what was available to them. No longer is this the case, as 2023 was a groundbreaking year in gastroenterology that redefined how clinicians can approach what was once an elusive, seemingly untreatable disease.
Benjamin Cohen, MD, clinical director for inflammatory bowel diseases at Cleveland Clinic, explained to HCPLive how limited the IBD treatment landscape used to be, especially for patients who did respond to available therapies but had to continue treatment because there were no alternatives. Recent advances in gastroenterology have ensured this is no longer the case “Now, we have other things to go to if what we're treating them with is not working. We don't have to necessarily settle for patients feeling unwell.”
Elizabeth Spencer, MD, assistant professor of pediatrics in the division of pediatric gastroenterology at Icahn School of Medicine at Mount Sinai, reflected similarly upon what IBD treatment used to look like, describing a lack of options for patients who did not respond to infliximab or adalimumab. Now, that is no longer “where the buck stops,” as she and other clinicians have more treatment options than ever before: “It's kind of opening up the world for [patients].”
Although this evolution was not instant, 2023 in particular was packed with landmark US Food and Drug Administration (FDA) decisions and first-in-class approvals that have proven to play a pivotal role in redefining what IBD treatment looks like. Among them was that of mirikizumab (Omvoh), which became the first and only FDA-approved interleukin-23 (IL-23) p19 antagonist on October 26.2
Spencer described IL-23 inhibitors as “game changers” because they bring a new treatment modality to IBD. Cohen added to this praise, commenting on “the power of their selectivity” and what they might bring to the table for patients, especially those with UC following the FDA approval of mirikizumab.
The decision for mirikizumab infusion (300 mg of 15 mL) and injection (100 mg of mL) was based on data from a pair of phase 3 trials within the LUCENT program. Results from LUCENT-1 and LUCENT-2 showed the treatment’s superiority to placebo for clinical remission; clinical response; endoscopic improvement; histologic-endoscopic mucosal improvement; and Urgency Numeric Rating Scale improvement for bowel urgency in patients with UC.2
In addition to IL-23 inhibitors, Cohen also reflected on the impact of JAK inhibitors reaching the market this year: “I think they’ve been the biggest advance because they’ve been so transformative for all sorts of patients.”
Upadacitinib (Rinvoq), a selective JAK inhibitor, played an equally pivotal role in shaping 2023 when it earned FDA approval for the treatment of adult patients with moderately to severely active CD who had an inadequate response or intolerance to ≥1 anti-TNF medications. Its approval for CD came on May 18, adding to prior indication for patients UC in 2022 and several other approvals for immune-mediated inflammatory diseases across rheumatology and dermatology in years prior.3
The decision for its use in CD was based on a pair of induction studies, U-EXCEED and U-EXCEL, as well as the U-ENDURE maintenance study, where it demonstrated superior rates of endoscopic response and clinical remission compared to placebo.3
“To have that option for Crohn's has been a game changer,” Cohen added, noting how JAK inhibitors have “changed the lives” of his patients who have not responded to other mechanisms of action.
Adelina Hung, MD, clinical assistant professor at Rosalind Franklin University of Medicine and Science and gastroenterologist at Sinai Health System Chicago, described the past year as an “explosion of new treatment options for patients” that has changed the landscape of how she and her peers treat IBD, also highlighting the addition of S1P receptor analogs as another major development.
Etrasimod (Velsipity), an S1P receptor modulator, was approved by the FDA for adults with moderately to severely active UC on October 13, based on data from the ELEVATE UC phase 3 registrational program including the ELEVATE UC 52 and ELEVATE UC 12 trials. It outperformed placebo for achieving clinical remission and attained statistically significant improvements in key secondary endpoints for endoscopic improvement, mucosal healing, corticosteroid-free remission, and sustained clinical remission.4
“I would say the number of new agents and classes for this year is really different than other years, and I think the exciting part for patients is that we have many more options,” Amy Stewart, CRNP, adjunct faculty at Georgetown University and lead APP with Capital Digestive Care, explained to HCPLive. “The challenging part for providers is keeping up with those options and figuring out how we position them in order to get the best outcomes for our patients.”
Beyond the advent of several new IBD medications, 2023 saw multiple FDA approvals for biosimilars and new treatment administration options that have increased access to life-changing therapies for patients with UC and CD.
“We now have so many options that we can be more selective in what may work for a particular patient from a safety perspective, mode of delivery perspective, a cost perspective,” Cohen explained.
Perhaps no development has made treatment more accessible than that of biosimilars, which are expected to provide greater access to biologic medicines for an additional 1.2 million patients in the US over the next 10 years. Further estimates project FDA-approved biosimilars could save patients and the health care system anywhere from $548 to $250 billion over their first 10 years on the market.5 For patients who may not be able to afford the originator drug, having a biosimilar option might be the only way they get the treatment they need.
“Even though we have all these new treatment options, for patients who lack insurance or don’t have typical commercial insurance, it’s a little bit tricky to get approved for them and we might not be able to choose it. There’s still some challenges in how we get the best medications for our patients,” Hung explained. “With my patients, insurance approval and costs are the main issue. Having the biosimilars allows us to give them the medication that they need at a more affordable cost.”
This year saw several FDA approvals for biosimilars, many of which came for adalimumab (Humira). The tumor necrosis factor-alpha (TNF-α) inhibitor’s initial approvals date back to 2007 and 2012 for CD and UC, respectively.6 Since then, several biosimilar options have earned approval and hit the market, providing many with more affordable treatment alternatives. Adalimumab-aaty (Yuflyma), adalimumab-afzb (Abrilada), and adalimumab-adaz (Hyrimoz) were among those introduced in 2023 alone.7,8,9 Additionally, ustekinumab-auub (Wezlana), an interchangeable biosimilar to ustekinumab (Stelara), was also granted FDA approval this year.10
Beyond the cost of treatment, Cohen explained how administration poses another barrier to access for many, calling infusions “limiting” and noting they might not always be a viable choice for patients: “To have those drugs available in a subcutaneous form increases options for them.”
Riha Bhatt, MD, assistant professor of pediatrics, pediatric gastroenterology, hepatology, and nutrition at Vanderbilt University Medical Center, voiced similar concern about the burden of infusions, describing it as “tough” to ask her patients to come in every 4-8 weeks for treatment: “I know that's very impactful to their life, so having a good option for both Crohn's and UC that’s subcutaneous or oral is a huge factor really impacting their quality of life positively.”
Vedolizumab and infliximab both saw subcutaneous administration approvals in 2023.11,12 Although these medications were previously available to patients in a different administration, Spencer pointed out their subcutaneous approvals are still significant because they give patients “the liberty of doing those treatments at home and not being tied to an infusion center.”
Although one cannot ignore the plethora of therapies that entered the IBD treatment landscape in 2023, clinicians’ use of these new options in practice and their ability to work with patients to navigate the evolving treatment landscape is what truly shaped this year in gastroenterology.
Spencer described it as a “tyranny of choice,” but she went on to explain how the surplus of treatment options has ultimately been a good thing for both patients, who now have an even wider array of treatment options to find something that works for them, and clinicians, who are better equipped to help their patients find success.
“I practice something called shared decision-making, and it really stems from truly listening to your patients' most desired things that they want fixed. Then you act from there and prioritize their priorities in order to choose a therapy,” she explained.
“I think it's hugely important that our outcomes involve both the objective measures, but also the patient symptoms,” Cohen added.
“Gastroenterologists are often focused on the objective endpoints of the biomarkers and endoscopic improvements, but patients need to feel better too.”
Bhatt expressed a similar sentiment, noting the importance of objective endpoints but pointing out the need to implement a patient-centric approach that addresses their symptoms and concerns. “Sure, we want to know if a patient achieves endoscopic remission on a certain medication, but the patients are still asking ‘Are you going to get my symptoms better in a way that impacts my quality of life where I'm not always running to the bathroom?’”
Although it may have been difficult, or for some, impossible, to manage bowel urgency and other complications in the past, clinicians are now equipped with a more comprehensive arsenal of treatment options to offer their patients relief from their most burdensome symptoms. From first-in-class therapies to biosimilars and subcutaneous administrations, 2023 truly had it all.
“This year in particular, we now have a plethora of therapies that we can offer our patients. I look at our toolbox, or toolboxes, and we have so many options for patients,” Kimberly Kearns, MS, APN-BC, nurse practitioner for DuPage Medical Group, explained to HCPLive. “Ultimately, this is going to lead to better patient outcomes, which I know is what we all want.”