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In a post-hoc analysis of the ADVANCE and MOTIVATE phase III induction studies, along with the FORTIFY maintenance study, researchers evaluated the safety profile of risankizumab (Skyrizi) in patients with moderate-to-severe Crohn's disease by age group. The analysis of the trials during the recent Digestive Disease Week (DDW) conference.

In this second of four exclusive roundtable episodes, 番茄社区app brought together three expert leaders in the field -- moderator of Baylor College of Medicine in Houston, is joined by , of Michigan Medicine in Ann Arbor, and , of Yale School of Medicine in New Haven, Connecticut -- for a virtual roundtable discussion on the safety profile of risankizumab by age group.

Following is a transcript of their remarks:

Hou: Our next abstract for discussion is an abstract by Dr. [Jean Frederic] Colombel looking at the safety of risankizumab in patients in different age groups, with a particular interest in patients in older age brackets.

Dr. Gaidos, do you have any comments about this abstract?

Gaidos: Yes, absolutely. So just a little bit of an introduction. So this is a post-hoc analysis of data from the induction studies for risankizumab, which were ADVANCE and MOTIVATE and then the maintenance study, which was FORTIFY. They took from this, all of the clinical trials, all of the phase III clinical trials, they broke the study subjects down by four age groups. So they had a <18, ≥18 to <40, ≥40 to <65, and then 65 to 80, and really looked at adverse events and adverse events in special interest by each of these cohorts.

I selected this study to talk about because we've been sort of inferring similar safety to ustekinumab [Stelara], but this really helps to again have more information to better discuss with our patients whether this is truly safe or not.

And they specifically looked at overall adverse events. They looked at serious adverse events. They looked at adverse events leading to discontinuation of therapy, serious infections, opportunistic infections excluding TB [tuberculosis] and herpes zoster. Then they looked specifically at herpes zoster. They looked at hypersensitivity, side effects, hepatic events, and injection site reactions. And really among the cohorts, there were no specific safety issues that arose for any of the cohorts, but particularly looking at those from 65 to 80.

So again, I thought this was really important because this is a new drug on the market. Patients always have questions about safety, particularly when we only have a couple years of clinical trial data, which we know those patient cohorts don't match what we see in clinic. The patients that come in the clinic tend to be sicker and have more drug exposures and risks for infections and concerns.

So I really liked that they broke this out into groups and broke down each of the potential adverse side effects, as well as looking at infections, so that we can discuss these findings with our patients.

Cohen-Mekelburg: I agree with Jill. I think the study confirms the safety profile of risankizumab in a clinical trial population. I think, important to note that it doesn't necessarily speak to the real-world experience, which I think will be very interesting as we begin to use it more and more.

Something to consider is that there really is a small percentage of older adults that are part of this study. I think it was 5% in the induction studies, and 8% in the maintenance study were between 65 and 80 years of age. I do completely give them props for actually incorporating inclusion criteria, patients up to 80 years old, which isn't done in a lot of studies.

And so to me, this is very nice, in particularly shared decision making as we talk to our older patients about safety. But again, it'd be interesting to see what happens as we get more real-world data.

Hou: Yeah, those are excellent points. I think that's one of the biggest questions that patients come and ask us about, right? When we're talking about new medical therapies, is safety. And it's encouraging as we're getting some of these newer agents, it looks like we are moving the needles, at least with the biologics, towards more favorable safety profiles. These are also encouraging, I guess sometimes being in IBD [inflammatory bowel disease], the advantage and disadvantage is these agents have had significant market experience in other disease states. So that again is an opportunity for us to have some experience outside the dosing is significantly different, and that data, of course, has to be taken in the appropriate context.

I was also very encouraged by the observation of signals, but I think as Shirley mentioned, in the end this was only about 80 patients in this age group. And the follow-up for induction and maintenance is only a year. And of course, we're worried more about long-term safety. So this is something that we'll need to see with more longitudinal data follow-up, and I'm sure we'll be seeing abstracts like this for meetings to come. So a nice addition.

Gaidos: It comes tumbling out, right?

Cohen-Mekelburg: One thing that I found very interesting, and I'm curious to your thoughts on this. One of the major issues that we faced clinically in beginning to prescribe risankizumab is the on-body injector. For us, it's really required us to train our nursing staff, and particularly in how they should educate patients to use this. And so we've been particularly cognizant of that and also of potential administration limitations. For example, patients who are older who maybe don't have the best fine motor skills or visual impairments, how would that affect administration?

And so to me, I think that's something that'll be very interesting. And I didn't really see any information in this abstract about barriers to use or misfiring as an example of an adverse effect, but I think that'll also be very interesting as we're beginning to use this more.

Gaidos: I would think the on-body injector would be easier than a syringe, as far as fine motor skills, because really you just kind of load it up, stick it on your body, and then hit go. And so I've been very interested since it's a whole new mode of delivery, I've been asking patients, does it hurt? Have you had any problems? Because I want to be able to tell other people what their experience has been.

And I would say most people haven't had any problems. I've had a couple patients tell me that the first time they use it, they kind of jump because they're not sure what to expect with the actual injection part. But I've also had patients tell me they don't feel anything and they think that it's not going in, but you can actually see the medicine inside and they say, well, it's going down and it's not leaking anywhere, so I guess I did it right. But yeah, it's been a learning experience for all of us.

Hou: Those are great points. To summarize this abstract again, thank you, Dr. Gaidos, for presenting it. We have some post-hoc analysis focusing on safety for risankizumab for Crohn's. It was showing encouraging findings without significant safety signals in the greater than 65- to 80-year-old patients. As we commented, some significant limitations in terms of the short duration that we have for follow-up in the clinical trial setting, as well as still a modest number of patients in this age group.

But to highlight, as Dr. Cohen-Mekelburg said, it's nice that they have included patients all the way up to the age of 80. And it gives us at least some data in this structured clinical trial format to look at some important things like safety outcomes.

So more to see as we see more data coming out and longer follow-up in this cohort. Thank you.

Watch episode one: Reaction to FDA's Approval of Upadacitinib for Crohn's Disease

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