311drug appears to work locally and not bioavailable systemically. Last, and perhaps
most novel, is that clinical remission was maintained for almost 3 months even
though the drug was administered for only 14 days.
Phase III studies are critical, more than for other compounds to confirm these
results [ 37 ]. The inclusion criteria in the phase II trial used only symptoms and not
more objective criteria for active disease, such as endoscopy. The median level of
C-reactive protein was low and 39% of patients did not have an elevated level.
Finally the endpoint also used only symptoms and did not include more objective
markers such as mucosal healing or normalization of fecal calprotectin or
C-reactive protein. These more objective inclusion criteria and endpoints are part
of the current phase III randomized control trial. The current trial is designed also
to better assess safety.
Of all the novel agents discussed in this chapter, this agent is potentially the most
transformative. Based on the available data and its mechanism of action, this agent
presents a possibly novel approach to treatment: short cycles of mongerson to
restore immunoregulatory processes and bring about a durable remission without
continuous maintenance therapy. A phase II randomized controlled trial in ulcer-
ative colitis is currently ongoing but not recruiting patients.
Conclusion
It is clear from the number and breadth of recently approved or late-stage develop-
ment agents that the treatment of IBD is expanding beyond anti-TNF therapy. These
novel agents are not novel because they are new but because they are interesting,
groundbreaking, and transformative. From novel strategies and mechanisms of
action to reduce inflammation, to introduction of oral therapy, to introduction of
possible intermittent therapy with antisense oligonucleotide therapy, each new
agent educates us on what are the key molecules in IBD and potentially one step
closer to a cure.
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17 Novel Agents in Inflammatory Bowel Disease