ORLANDO, FLA. – Biologics used to treat inflammatory bowel disease could be more effective if they were used earlier in patients with these conditions, according to an expert.
“The earlier the better in patients who need them,” said Dr. Stephen B. Hanauer, professor of medicine at Northwestern University (Chicago) and medical director of the school’s Digestive Health Center. “Biologics should be used with short-term combination therapies and with therapeutic drug monitoring.” Dr. Hanauer made his remarks at the most recent annual Advances in IBD meeting sponsored by the Crohn’s and Colitis Foundation of America.
Currently, most clinicians regard the use of immunomodulators in inflammatory bowel disease as a “last ditch effort” treatment, and turn to them only after patients fail first-line therapies. Similarly, guidelines in the field recommend immunomodulation for moderate to severe disease, the time when Dr. Hanauaer said “the disease has progressed to the point where there is already the structural damage we’re trying to prevent.”
Instead, he believes IBD sufferers would benefit from prospective trials that show earlier intervention yields higher remission rates, particularly in steroid-naive populations.
“We should learn from the rheumatoid arthritis people who figured out that administering highly effective agents earlier has the potential to modify long-term disease behavior,” Dr. Hanauer said.
Studies cited by Dr. Hanauer indicated that when biologics were introduced when patients were steroid- and immunosuppressive-naive, remission rates doubled, up to two-thirds of patients compared with only a third of patients who were given combination therapy. The results held as early as 26 weeks and at 1 year follow-up. “When we gave biologics on top of the other therapies, they offered no advantage.”
That the drugs are more widely used in rheumatoid conditions has also impacted dosing levels, said Dr. Hanauer, who said that much higher doses likely would yield better remission rates, particularly in Crohn’s disease. Not dosing at the correct levels, Dr. Harnauer said, can lead to serum troughs that diminish the patient’s response to treatment, and put them at risk of immunogenicity. “Trough levels can be used to predict clinical remission,” he said. “The problem is that we don’t have very good prospective data on it.”
Dr. Bruce E. Sands, chief of gastroenterology at Mount Sinai in (New York), and another presenter who spoke about biologics in IBD at the meeting, agreed. “When a patient fails the first anti-TNF, the question is whether it has been adequately dosed, particularly in the case of severe ulcerative colitis where we’re really starting to understand that we need higher doses to get the disease under control.”
As for earlier intervention in ulcerative colitis with biologics, Dr. Sands believed the timing is more fluid. “It really is your choice and the patient’s choice,” he said. The same was true for the recent addition of the biologic vedolizumab to the ulcerative colitis armementarium, he said, noting that there is a response both during induction and maintenance phases for all biologic therapies in ulcerative colitis.
Although infections and neoplasm are concerns with all biologic therapies, Dr. Harnauer downplayed the risks when compared to corticosteroid therapy, particularly in Crohn’s disease. “The risk of neoplasia in patients given anti-TNF (anti-tumor necrosis factor) therapy disappears after adjusting for the use of azathioprine,” he said.
Dr. Sands was less sanguine about the potential risks of anti-TNF treatment, reminding the audience that the drugs carry black box warnings from the U.S. Food and Drug Administration, and that patients must be screened for their candidacy before administering immunomodulation therapy. “It is possible to develop a variety of autoimmune disorders, and immunogenicity with these drugs,” said Dr. Sands, also adding that a risk of demylenating disorders must also be accounted for. “Make sure you monitor your patients, and that you explain the risks to them.”
Regardless of when biologics are used in treatment, both presenters agreed that their exorbitant cost is an issue. “We cannot use them for every patient who walks through the door,” said Dr. Sands.
For Dr. Harnauer, the cost stands in the way of the earlier positioning of the drugs in treatment algorithms. “If we were talking about a treatment that only cost a few dollars, we wouldn’t be worrying about any of this.” Prospective pharmaco-economic studies that go beyond measuring the in-patient and surgical costs, but account for the timing and use of biologics could help strengthen the case for earlier treatment, he said.
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