Not dead yet: The role of immunomodulators in IBD
ORLANDO — Thiopurine immunomodulators represent a potentially inexpensive and effective method for inflammatory bowel disease maintenance that can be underused as biologics became available, according to a keynote presentation from Advances in Inflammatory Bowel Disease 2019.
“The challenge in our field is that all these other therapies are being marketed by drug companies and there’s no one marketing thiopurines,” Stephen B. Hanauer, MD, medical director of the Digestive Health Center at Northwestern University Feinberg School of Medicine, told Healio Gastroenterology and Liver Disease. “I have to go back to my predecessors and point out that these were pioneers who have demonstrated a role we now need to put into perspective with all the other therapies that are available.”
Hanauer explained that, before biologics were available, maintenance options included the thiopurine immunomodulators azathioprine and mercaptopurine, which demonstrated steroid-sparing effects and maintained remissions in early studies from the 1980s and 1990s. This was especially true for azathioprine in Crohn’s disease cases.
Later into the 2000s with the introduction of early biologic studies, however, clinical data showed that while there was no significant difference in treating patients with thiopurines or biologics alone, patients responded particularly well to combination therapy.
“As with many things in life, there has been a pendulum swinging back and forth,” Hanauer said, regarding the number of studies reviewing outcomes of either treatment method. Following this, he highlighted the side effect profile and risks related to thiopurines, including lymphoma and non-melanotic skin cancers.
“How do the societies view this? Basically, all of those guidelines, including within the past 2 years with the ACG guidelines, have advocated thiopurines for steroid-sparing maintenance of remission after steroids have advocated a role in combination therapy,” he said. “The AGA guidelines in postoperative Crohn’s disease also say that there is benefit of azathioprine in maintaining postoperative remissions. So, we have three areas where thiopurines are effective: maintenance after steroids, in combination with TNF inhibitors, and preventing postoperative recurrence.”
Hanauer concluded that physicians should not “throw the baby out with the bath water” when it comes to immunomodulators for patients with IBD between the cost-saving benefits compared with the “tens of thousands of dollars a year” spent on biologic therapy and the documented benefits.
“I believe there is a role when they are used correctly. If you can reduce the number of patients who are going to require biologics, it makes sense to utilize them,” he said. “There still is a role for these. Why not try thiopurines after steroid therapy, give them for 8 weeks or 16 weeks, and if they’re not effective, you're in position to give biologics. Just like every other drug that we are using now, it requires some form of therapeutic drug monitoring to optimize the benefits.” – by Talitha Bennett
Reference: Hanauer SB. Immunomodulators in 2020: Dead or Alive? Presented at: Advances in Inflammatory Bowel Disease; Dec. 12-14, 2019; Orlando.
Disclosure: Hanauer reports that he conducts clinical research for AbbVie, Amgen, Celgene, Genentech, GSK, Janssen, Lilly, Luitpold/American Regent, Novartis, Novo Nordisk, Pfizer, Prometheus, Receptos, Sanofi-Aventis, Takeda, UCB Pharma, and Luitpold/American Regent; consulting for AbbVie, Actavis, Amgen, Arena, Astellas Pharma Global, Astra Zeneca, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Catabasis, Celgene, Celltrion, Cellceutix, Cubist, Ferring, Forest Labs, Genentech, Glenmark, GSK, Hospira, Janssen, Lilly, Luitpold/American Regent, Meda, Merck, Nestle, Novartis, Novo Nordisk, Pfizer, Prometheus, Receptos, Salix, Sanofi-Aventis, Seattle-Genetics, Seres Health, Shire, Sun Pharmaceuticals, Takeda, Theradiag, TiGenix, UCB Pharma, VHsquared; performs data and safety monitoring for Bristol-Myers Squib; and he is a speaker for AbbVie, Janssen, and Takeda.