Lead study author, Edward V. Loftus Jr, MD, a gastroenterologist at the Mayo Clinic in Rochester, MN, discussed study highlights in an interview with GI & Hepatology News.

What is the main clinical take-home message of this trial?

Dr. Loftus: The results overall are reassuring and overall, the benefit-risk profile for most IBD patients is favorable. However, it is important to recommend zoster vaccination in patients who have started or are about to start upadacitinib.

When you had all the data in front of you, was there a finding, or perhaps more than one, that surprised you?

Dr. Loftus: I was somewhat surprised to see that there was no elevated signal for MACE even in the high cardiovascular risk subgroup. This was defined by age, smoking (current or within 15 years) obesity, cardiovascular history, diabetes mellitus, hypertension, thromboembolism, etc.

Why is this research important? What gap(s) in knowledge or therapeutics does it seek to fill?

Dr. Loftus: We often talk about the efficacy and safety of new therapies in isolation. Upadacitinib is highly potent and fast acting in IBD, but the label carries boxed warnings. In this post hoc analysis of over 2,000 IBD patients in pivotal trials of upadacitinib, we looked at the efficacy and safety of upadacitinib side by side in subgroups of interest, including in those with either low or high cardiovascular risk, those with either prior biologic treatment failure (including anti-TNF specifically) or not, and in age subgroups. The efficacy of upadacitinib was higher than placebo in all of the subgroups, and safety wise the subgroups were comparable between upadacitinib and placebo except for a signal for herpes zoster in Crohn’s patients on upadacitinib and a nonsignificant higher rate of serious infections in Crohn’s patients on upadacitinib.

What additional research may be needed/what questions remain unanswered?

Dr. Loftus: Longer follow-up of patients on upadacitinib for IBD will help answer questions about the long-term safety of this drug.

Are there limitations to the study you’d like to acknowledge?

Dr. Loftus: First of all, this was a post hoc analysis, not prespecified.  Although there were over 2,000 patients in this analysis, it still might not be big enough to detect small differences in safety outcomes especially for less frequent events.