Smarter, earlier, deeper: Choosing an initial IBD therapy
There are many different treatments for inflammatory bowel disease, and choosing the right one for a patient with a new diagnosis can be a challenge.
In a virtual presentation for the Interdisciplinary Autoimmune Summit, Adam Cheifetz, MD, director of the IBD center at Beth Israel Deaconess Medical Center, said to optimize therapy, physicians need to think about treating smarter, earlier, deeper, to a targeted goal and more effectively.
“At the time of diagnosis use certain clinical factors, including serology and genetics, and in our case endoscopy, to try to predict which patients are going to have a more severe disease course and a more high-risk disease,” he said. “In those patients, we’ll consider early biologics and even combination therapies.
“In the end, what we want to do particularly for these high-risk patients, is change the natural history of the disease, which we know is progressive, destructive and often leads to surgery.”
While predicting high-risk disease can be tricky, Chiefetz said factors to look for include early age at diagnosis, extensive anatomic involvement and perianal disease in Crohn’s disease. In ulcerative colitis, many of the same factors apply in addition to a need for steroids. In both cases, patients with deep ulcers likely have more extensive disease, Chiefetz said.
Once patient risk is assessed, it is important to provide treatment early with an effective therapy. Cheifetz said early on, there is a “window of opportunity” to help patients avoid severe disease complications.
“Even without symptoms, the disease can continue to progress and patients can continue to develop complications, including strictures, fistulas, abscesses, which can lead to surgery,” he said. “What we would like is to intervene before the complications can develop, really treating the disease while it’s still inflammatory.”
Looking at data from five pivotal studies of anti-TNF agents in IBD, Cheifetz said that longer disease duration has an adverse effect on outcomes. In the Step Up Top Down trial, which included patients with a disease duration of less than a year, the percentage of patients with CD in remission was about 70%. In the ACCENT1 and CHARM trials, which included patients with disease durations of between 8 and 10 years, the percentage of patients in remission was as low as 40%.
When selecting an agent for a patient with new-onset IBD, it is important to set goals and share that decision making with the patient, Cheifetz said. Studies have shown that resolution of clinical symptoms are not sufficient, and goals should include both clinical and endoscopic improvement in both UC and CD.
“A lot of the push for endoscopic healing comes from evidence that healing is associated with better long-term outcomes,” Cheifetz said. “Less flares, complications and hospitalizations.”
When he first meets with patients, Cheifetz tells them he wants them to feel like they did prior to their diagnosis of IBD. In fact, he wants them to forget they even have IBD other than to remember to take their medication.
“The minimum goal I set for patients is corticosteroid-free clinical remission,” he said. “But I do talk to them about endoscopic improvement and remission as a goal and something we will aim for. If a patient is in clinical remission but hasn’t seen that endoscopic improvement, I will optimize whatever therapy that patient is on. The more difficult decision is when the only option is to switch mechanisms.”
Comparative effectiveness studies have shown that a combination of Remicade (infliximab, Janssen) and azathioprine is better than infliximab alone, which in turn is better than azathioprine alone in patients with CD naive to biologic and immunomodulator therapy. In a short-term trial of patients with UC, combination of infliximab and azathioprine was more effective than either drug on their own. In the VARSITY study, the first head-to-head study of biologic agents, researchers found that Entyvio (vedolizumab, Takeda) was more effective than Humira (adalimumab, AbbVie) in patients with moderate-to-severe UC.
‘There are many other trials underway, which should be very helpful in making our decision easier,” Cheifetz said.
Whatever the initial therapy, Cheifetz said it is critical to treat aggressively by ensuring patients have the dosing they need to achieve better outcomes, as well as avoid adverse events and immunogenicity. He suggested using proactive therapeutic drug monitoring as a strategy to achieve the necessary drug concentrations.
“We know that the first agent we use is best, and TNF-exposed patients do not respond as well as TNF-naive patients,” he said. “There is a high rate of secondary loss of response, and the risk for developing anti-drug antibodies, particularly among the anti-TNF agents, is not insignificant.”
If a physician is not using proactive TDM, they should be using a combination therapy with infliximab and likely another anti-TNF.
With so many medications and mechanisms of action, Cheifetz said choosing the right agent needs to be tailored to the individual.
“It does come down to shared decision making,” Cheifetz said. “So have an open and honest discussion with your patient and hear them out.”