At his Internal Medicine Meeting 2019 session “Inflammatory Bowel Disease Potpourri,” CDR Manish Singla, MD, FACP, offered an update on new biologic therapies for inflammatory bowel disease (IBD), as well as pearls on inpatient treatment of the condition.
New and old drugs
The biologics approved most recently—vedolizumab, ustekinumab, and tofacitinib—are usually much more expensive than older medications, which can complicate prescribing, said Dr. Singla, who is an assistant professor in the department of internal medicine at Walter Reed National Military Medical Center in Bethesda, Md.
“You have to go through authorizations, you have to contact the patient's insurance company,” he said. “But the attraction of the new biologics is that they may come with lower risk profiles and easier delivery.”
Vedolizumab, the only new agent delivered as an infusion, is given over 30 minutes and doesn't require premedication. “Our patients [that] we've switched from infliximab to vedolizumab are very excited that they get out of their infusion unit within an hour,” Dr. Singla said. Studies have not found any increased risks with vedolizumab versus placebo, and patients can receive live vaccines while taking it. Dr. Singla said he believes vedolizumab has more of a role in ulcerative colitis than in Crohn's disease but noted that it is FDA-approved for both conditions.
Ustekinumab is delivered as one IV dose initially and then is self-administered subcutaneously thereafter. It is associated with increased risk of serious infection during induction, as well as an increased risk of nonmelanoma skin cancer. Patients should be tested for tuberculosis before receiving this drug, Dr. Singla said.
Tofacitinib is the first oral biologic approved for IBD, Dr. Singla said. “The oral part of it, I think, is very attractive to patients. They don't have to inject themselves with needles. They don't have to come in to infusion centers,” he said. Patients taking this drug should not receive live vaccines, and complete blood count should be monitored, he said.
Despite its advantages, tofacitinib is associated with an increased risk for infection and increased LDL cholesterol level, as well as a very high risk for herpes zoster, Dr. Singla said. In addition, data from early 2019 found an association with increased risk for venous thromboembolism (VTE), particularly at the high dose used for induction in ulcerative colitis. As a result, Dr. Singla said, “The recommendation right now is to go back to the maintenance dose as we get more phase 4 data.”
Of the older tumor necrosis factor (TNF) biologics, infliximab is given as an infusion over two hours, while adalimumab, golimumab, and certolizumab are administered by self-injection over a number of weeks, he said. All four drugs are associated with increased risk for lymphoma, and Dr. Singla offered advice on how to communicate that risk to patients.
“The way that I usually describe it is that if you have IBD, you have about a two in 10,000 risk of having lymphoma, and if you are on a TNF biologic, you have about a six in 10,000 risk of developing lymphoma. So yes, that is three times the increased risk, but the absolute risk of lymphoma is low,” he said. “It still scares a lot of patients.”
The rate of allergic reactions, meanwhile, is 10%, he said, including increased heart rate during the infusion and rash at the injection site as well as more serious problems like anaphylaxis. Patients beginning these drugs should be tested for tuberculosis and hepatitis B beforehand, and complete blood counts and C-reactive protein levels should be checked annually, he said. Also, Dr. Singla noted, “We can't give them live vaccines while they're on therapy . . . . Remember, give them their live vaccines when you diagnose them, even before they need therapy, so this does not become a problem later.”
Speaking of problems, when a patient with IBD presents to the hospital, the first one you should look for is Clostridium difficile infection. C. diff is extremely common in this population, said Dr. Singla.
A national survey published in the American Journal of Gastroenterology in 2008 found that patients with ulcerative colitis had a prevalence of 37.3 per 1,000 and patients with Crohn's disease had a prevalence of 10.9 per 1,000, versus 4.8 per 1,000 among GI patients without IBD and 4.5 per 1,000 among general inpatients. C. diff infection was also associated with higher mortality among patients with ulcerative colitis and longer length of stay in all IBD patients.
“We recommend for all patients who come in to be hospitalized for IBD to get screened with a C. diff [polymerase chain reaction] when they come in the door,” Dr. Singla said.
In IBD patients with severe colitis, the American College of Gastroenterology has advised that clinicians may need to order simultaneous empirical therapy for C. diff infection and immunosuppressive treatment for IBD before the results of the C. diff test are back, Dr. Singla said. “IBD patients who are on immunosuppression can continue their immunosuppression if they have C. diff infection, as long as you're treating their C. diff infection. And this comes up,” he said. “People who come in with a hemoglobin of 10, a [C-reactive protein] of 12, they are actively flaring with their colitis. When you check their C. diff, it's positive. Treat both.”
Patients hospitalized with IBD also have a high risk for VTE, Dr. Singla said, especially those younger than age 40. Another study published in the American Journal of Gastroenterology in 2008 found odds ratios of 1.85 for VTE in discharged patients with ulcerative colitis and 1.48 for those with Crohn's disease versus discharged patients without IBD. Length of stay was longer and hospital charges were higher in IBD patients with VTE, and an annual 17% increase in odds of VTE in patients with IBD was seen over a seven-year period.
“One of the things that we try to teach our interns and residents is that just because they are bleeding, because they are flaring, doesn't mean you shouldn't give them chemoprophylaxis for VTE,” he said. “And so yes they're bleeding, yes their hemoglobin is low, but give them chemoprophylaxis.”
Dr. Singla next moved on to the use of opioids for hospitalized IBD patients. “I don't think I have to tell this audience that opioids are bad, but opioids are bad,” he said. He noted that about 5% of patients with IBD are heavy opioid users and have three times the mortality of their counterparts. In addition, they have increased length of stay during their hospitalization and a 40% increased risk of readmission within 30 days.
Some of this opioid use is related to physician discomfort, since managing pain in patients admitted for IBD can be frustrating, Dr. Singla acknowledged. “They're young, they say they've got abdominal pain, nothing's making it better. You know that they have IBD. You call for a gastroenterologist, and they're not coming back in until the morning, and so what do you do with these patients overnight?”
He advised his audience to do their best to hold the line by saying something like, “Listen, narcotics are not the best answer for you. We'll try to keep you NPO to not stimulate your bowels. We'll wait for gastroenterology to come in,” he said. He recommended prescribing acetaminophen rather than ketorolac, but “Pain is pain, and I think treatment of pain is important . . . . Try to avoid opioids as much as you can.”
Dr. Singla's final piece of advice for his audience was to get surgeons involved with patient care early. “Your patient comes in with a low hemoglobin, a high [erythrocyte sedimentation rate], and a low albumin. Those are bad prognostic factors that we're going to be able to medically treat these patients,” he stressed.
Surgeons can help with early management of strictures and early referral for colectomy, he said. In addition, Dr. Singla noted that surgeons typically have a much more aggressive approach to starting patients on total parenteral nutrition and peripheral parenteral nutrition, in part because poor nutritional status leads to more surgical complications. Last but not least, earlier involvement of the surgical team may help with patient buy-in when it's time for a surgical procedure, he said.
“I'm sure many of you have seen patients who need a colectomy, don't want an ostomy, no colectomy at any cost, but they're still pooping 12 times a day with blood,” he said. “I think having them talk to surgeons early gets them a little bit more comfortable with the idea.”