LAS VEGAS – Biologics have dramatically improved the treatment of Crohn’s disease (CD), an influential gastroenterologist told colleagues, but there is still no clear evidence suggesting which ones are best as first-line treatments.
Randy Dotinga/MDedge News
Dr. Gary R. Lichtenstein
When it comes to making a choice, insurer policies may play a role, said Gary R. Lichtenstein, MD, lead author of the American College of Gastroenterology’s 2018 treatment guidelines for CD. Otherwise, “you’re left with clinical factors, your own judgment, and some indirect data,” said Dr. Lichtenstein, professor of medicine at the University of Pennsylvania, Philadelphia, who spoke about the guidelines in a presentation at the Crohn’s & Colitis Congress – a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Lichtenstein spoke about recommendations regarding treatment of CD in several areas. The following is a summary of some points he made:
Diagnosis: Some tests aren’t recommended
Classic signs and symptoms of CD include abdominal pain, diarrhea, fatigue, weight loss, failure to grow, anemia, and manifestations outside the intestines. Fecal calprotectin testing is recommended to differentiate inflammatory bowel disease from irritable bowel syndrome; genetic testing and serologic markers are not recommended for diagnosis.
Ileocolonoscopy is recommended for diagnosis and provides details about severity. Several factors suggest higher risk of progressive disease: Young age at diagnosis, initial extensive bowel involvement, perianal/severe rectal disease, and penetrating or stenosing phenotype at diagnosis.
Research is hinting that visceral adiposity may be a risk factor too, Dr. Lichtenstein said, adding that “the greater the number of poor prognostic factors, the worse the likelihood of needing a colectomy.”
Focus of treatment: Don’t just consider symptoms
For patients with moderate to severe disease, guidelines now suggest that physicians not just focus on symptoms but also consider endoscopic signs of response and healing. Guidelines also recommend paying attention to quality of life and levels of stress, anxiety, and depression.
Drug therapy: Biologics stand apart
Budesonide is appropriate for induction therapy in mild to moderate CD. There are many possible treatments for moderate to severe disease, including steroids for induction and thiopurines or methotrexate for maintenance
But biologics stand apart, Dr. Lichtenstein said, noting that “they have really been the mainstay of the treatment of our moderate to severe patients.”
Still, he cautioned that tumor necrosis factor (TNF) inhibitors are linked to a variety of adverse effects, including demyelination, heart failure, auto-immunity, infusion reactions, immunogenicity, infection, bone marrow suppression, and cancer. Specifically, the risk of lymphoma and melanoma may go up, although the absolute risk is low.
He added that a third of patients will not respond to TNF inhibitors, and about half of those who do respond may stop responding after a few years.
Among newer drugs, vedolizumab (Entyvio) is useful as an induction and maintenance drug in CD. “We recognize it has a slow onset of action,” Dr. Lichtenstein said. “Waiting is part of what one needs to do. Those who had prior anti-TNF failures are less likely to respond than those who have been anti-TNF naive.”
The drug has a favorable safety profile, he said.
Ustekinumab (Stelara) also has a favorable safety profile with very low infection risk, although Dr. Lichtenstein said he expects that the drug will be linked to a small increased risk of cancer. “Perhaps I’ll be wrong,” he said, “but time will tell.”
So which biologic is best? Direct head-to-head trials are lacking, Dr. Lichtenstein said. However, a 2018 systematic review and network meta-analysis analyzed clinical trial data and came to these conclusions: Infliximab (Remicade) and adalimumab (Humira) are best for induction of remission in biologic-naive patients; adalimumab and ustekinumab are best for induction of remission in TNF inhibitor–exposed patients; adalimumab and infliximab are best for maintenance of remission; and ustekinumab and infliximab are best in terms of lowest risk of adverse events or infection (Aliment Pharmacol Ther. 2018 Aug;48[4]:394-409).
Dr. Lichtenstein reports many disclosures with multiple drugmakers, including both grants/research support and consulting relationships with Celgene, Janssen Biotech, Salix, Shire, UCB and Warner Chilcott.