Positioning Therapeutic Agents for IBD

When choosing which therapeutic agent to use when treating patients with inflammatory bowel disease (IBD), Miguel Regueiro, MD, goes through a careful checklist to weigh and balance comorbidities, special conditions such as pregnancy, and the known risks of various agents, he said at the July 25 virtual Advances in Inflammatory Bowel Disease (AIBD) 2020 regional meeting.

Dr Regueiro is professor and chair of gastroenterology, hepatology, and nutrition at the Digestive Diseases and Surgery Institute at the Cleveland Clinic and is a cochair of the AIBD 2020 events.

During his session on July 25, he reviewed the current landscape of therapies for in IBD, noting the risks, benefits, and experience in using anti-tumor-necrosis-factor (TNF) agents, anti-integrins such as vendolizumab, interleukin (IL) 12/23 inhibitors such as ustekinumab, and Janus-kinase (JAK) inhibitors such as tofacitinib.

He explained that anti-TNF agents, which present risks of infection and lymphoma, have the longest history in IBD therapy, while the JAK inhibitor is “the new kid on the block,” whose risks are not completely defined. Vedolizumab and ustekinumab both have excellent safety profiles and low immunogenicity, he stated.

The speed at which these therapeutics can treat IBD successfully is important, because the sooner patients with Crohn disease (CD) and ulcerative colitis (UC) achieve remission, the less likely they are to experience fistulas and abscesses, require surgery, or develop stricture. Faster treatment equals better long-term outcomes, Dr Regueiro explained. However, he noted that while biologics are best introduced at diagnosis, “before damage occurs,” they are often introduced only after the patient begins to develop fistulas and abscesses. "Ultimately there is a tipping point beyond which we cannot achieve tight control of disease and surgery is required" if disease progresses too far, he said. He also reviewed the definitions of remission in both UC and CD.

Treatment strategies for UC and CD are driven by the risk of a patient developing complicated disease, Dr Regueiro said. Patients with UC with a limited anatomical extent and mild endoscopic disease are at low risk for colectomy. However, patients older than 40 years with extensive disease, deep ulcers, and a history of hospitalizations who are steroid-dependent and have had infection with Clostrioides difficile and/or cytomegalovirus are at high risk for surgery. Repeated courses of steroids can also cause patients to move into the high-risk group. A systematic review, infliximab and vedolizumab showed the highest efficacy for induction in higher-risk patients. "We also want to look at high-risk patients more closely and often." 

In patients with CD, patients older than 30 years at the time of diagnosis who have limited anatomical involvement, no perianal or severe rectal disease, no prior surgical resection, and no strictures are considered at low risk for rapid progression of their disease. However, patients with one or more of these complications are considered at high risk for rapid progression. "If you see deep ulcers, these patients need to be treated more aggressively from the start," he said, noting that more than 80% of Crohn disease patients are classified as high-risk. Research shows that for first-line induction therapy for moderate to severe Crohn disease, adalimumab and infliximab have the strongest effect. 

He reviewed a checklist that he uses in his own practice when assessing therapeutics for treating his patients, which includes severity of disease, level of risk, age, and other factors. He also noted that many health insurers will require patients use an anti-TNF therapy before other agents, such as tofacitinib, will be approved.

Overall, Dr Regueiro said, “safety influences positioning. Prevention is the best way to avoid complications.” That includes ensuring patients with IBD have the appropriate vaccinations and baseline monitoring. “If an event occurs, ask questions, including ‘Is this related to IBD itself or to the medication?’” He also stressed, “Age matters. If your patient is older than 60 years, consider biologic monotherapy and carefully weigh the risks and benefits of biologics.”

Dr Regueiro ranked therapies on a safety pyramid, with steroids at the bottom, followed in ascending order by thiopurine/anti-TNF combinations, thiopurine monotherapy or tofacitinib, anti-TNF monotherapy, and vedolizumab and ustekinumab at the top. "It doesn't mean we shouldn't be using the drugs at the bottom, if the patient needs it."

He added this reminder for physicians trying to balance safety and efficacy: “Inadequate treatment is an adverse event.”

—Rebecca Mashaw

Reference:

Regueiro, M. Positioning anti-cytokines and anti-integrins in IBD management. Presented at: Advances in Inflammatory Bowel Disease 2020 regional, Chicago; July 25, 2020; virtual.