ORLANDO – A range of novel therapies are set to come online for the treatment of inflammatory bowel disease (IBD), but they will miss the mark when it comes to meeting the need for better, longer-lasting outcomes, according to one expert.
“We’re positioning our therapies all wrong,” Dr. Stephen Hanauer said at a conference on inflammatory bowel diseases sponsored by the Crohn’s and Colitis Foundation of America.
Dr. Stephen Hanauer
“In psoriasis, patients are immediately given effective treatment with ustekinumab, but in IBD, we have to wait for patients to fail multiple therapies before they are given an effective one,” said Dr. Hanauer, who is the Clifford Joseph Barborka Professor of Medicine in the division of gastroenterology and hepatology at Northwestern University, Chicago. The result, he said, is that after first-line therapies in IBD have been used to diminishing effect, patients typically have waited up to between 6 and 10 years before they are given the treatment that works best for them. By then, when a patient likely has experienced penetrating disease and fistulas, even the most effective therapy has less than a 50% chance of working well.
This upside down state of affairs in the field is due to a combination of factors. Since the 1998 introduction to the U.S. market of infliximab for treating Crohn’s disease, much has been learned about the characteristics of IBD, including that it is a chronic, progressive condition with a higher burden of inflammation than is necessarily indicated by clinical symptoms.
But at the time infliximab was introduced, it was viewed not as a first-line treatment that could prevent further disease, but as a last ditch effort to halt an already rampant disease state that typically had its roots of destruction well planted long before the patient presented clinically, according to Dr. Hanauer.
In the last 2 decades, however, numerous studies have shown that earlier intervention with biologics results in higher treatment response rates and less structural trauma. []
In addition, data indicate that administering the correct choice of anti–tumor necrosis factor (TNF) agent in biologic-naive patients will yield as much as a 20% greater response rate, which could lead to lower costs. “Long-term pharmacoeconomic data are needed to include not only direct costs of care, but also indirect costs that capture lost income, productivity, [and] disability,” Dr. Hanauer said in an interview.
As it stands now, even vedolizumab, indicated in 2014 for use in both Crohn’s disease and ulcerative colitis, is kept for an even later stage of disease in the standard algorithm, coming behind not only “severe stage of disease” but placed after a patient has failed other anti-TNF treatment.
Biologics are far safer than the corticosteroids, which precede them in the typical treatment algorithm, but because cost is king, according Dr. Hanauer, “it’s the cost that drives our later-stage intervention … if anti-TNFs cost a dollar, we’d use them in everything.”
“We would see more impact if we move these therapies earlier into treatment,” he said. “Now we give the patients least likely to respond to these treatments, the [costliest] therapies,” Dr. Hanauer said during his presentation.
Meanwhile, the several novel IBD therapies in development are primarily being tested for late-stage disease. Changing the criteria for inclusion in such clinical trials could mean future treatment is more cost effective. “Study sponsors could go after ‘earlier’ indications in the mild to moderate range,” he said in the interview.
To improve the treatment algorithms already in use, Dr. Hanauer said clinicians should learn more about the pharmacokinetics and pharmacodynamics of their armamentarium, something he said most clinical trials tend to ignore. “Most [IBD] drugs were developed for rheumatoid arthritis where these kinds of considerations are not as important since they have many more ‘tools’ [to choose from] in rheumatology. In IBD, we have had to make the best of our limited tools. Industry would prefer to keep things simple, but it isn’t.”
Also availing themselves of therapeutic drug monitoring would help clinicians ensure that patients have high enough blood levels of their treatment at the time they complete induction therapy, making the management phase easier, Dr. Hanauer said.
Redefining disease severity will mean that new treatments will have more efficacy, and can lead to more opportunities for novel treatments to work. Until then, leaving biologics to be the agent of last resort means, according to Dr. Hanauer, there are more patients “who have none of the benefit and all of the risk.”
Dr. Hanauer reported several relevant financial disclosures, including AbbVie, Actavis, Hospira, Janssen, Novo Nordisk, and Pfizer.