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Head-to-Head Comparison of Ustekinumab and Adalimumab in the Treatment of Moderate to Severe Crohn's Disease
Dr. Naik: A very compelling study I wanted to talk about first touches on an area in inflammatory bowel disease that we have, hopefully, now been spoiled with, and now, in terms of all our myriad therapeutic options. And what we need now is a better ability to position therapies and compare these therapies head-to-head.
So a really great endeavor by Bruce Sands and William Sanborn and many others was the SEAVUE study, where we utilized ustekinumab
SEAVUE Study Design
And it was comparison of ustekinumab and adalimumab head-to-head in the therapy of moderate to severe Crohn's disease. And so they basically looked at this in biologic-naive patients, and they looked at one year outcomes. Basically, it looks at using the Crohn's disease activity index greater than or equal 220 or less than 450, and meeting failure or intolerance of steroids or immunomodulators only. And needed at least one ulcer on ileocolonoscopies. So was a multicenter, randomized, blinded, parallel-group, active-controlled study with a primary endpoint of CDAI at week 52. And they did have endpoints treated in that hierarchal action. And if an endpoint failed to reach statistical significance, the endpoint analyses were exploratory only, as per standard.
So really kind of a middle, 30 year-old average patient population. Disease duration ranged anywhere of actually, importantly, less than three years on the average. With elevated fecal calprotectins and other objective markers of inflammation. And the surgical burden was about 20% in these patients.
Study Findings
And looking at clinical remission, importantly, the crux of the matter here is that there weren't any significant differences in primary or secondary endpoints between the two therapies, as studied. And it's important to look at in terms of in CDAI less than one in 150, patient reported outcomes, symptom remission, and endoscopic remission, defined as SES-CD score less than or equal to 3, which are pretty routine and standardized ways to measure these trials.
Importantly, also, which is important whenever we consider biologic therapies, there were no new major safety signals, really, amongst both treatment arms. What's important to know for this study and in our practice is that while there weren't major differences, it was the first head-to-head study of biologics in patients with Crohn's disease, and they showed pretty high efficacy before adalimumab and ustekinumab. So putting the comparisons aside, we had seen clinical remission in about 60%, which is pretty good, when all things considered in patients' symptoms, et cetera.
But we must know that in our practice, we have always finded and needed to modulate dosing and personalized therapy. And this wasn't allowed in this study and, frankly, understandably adds a layer of complexity when we're evaluating patients. So remember, combination therapy with immunomodulators and any dose escalation wasn't allowed. So it probably doesn't affect our full, current real-world practice, but it does reassure us in the sense of they're very effective treatment for Crohn's disease. And there was a slight signal for lower discontinuation rates, in ustekinumab, but I think that bears further evaluation in more of a real-world practice.
PracticeUpdate: Does dose escalation lead to differences between the two therapies?
Dr. Naik: So dose escalation is something that we've been used to quite a long time in the treatment of inflammatory bowel disease. Certainly with adalimumab. While studied, and essentially I must mention that this is not the label-approved dose for adalimumab. Well, you've utilized various sets, setting of inflammatory burden and potentially even therapeutic drug monitoring in those patients with severe inflammation. And so I would say that if you use adalimumab, you have escalated adalimumab. And so it really kind of puts that into perspective, especially looking at low albumin rates, higher degrees of inflammation, inflammatory burden, different disease phenotypes, more severe Crohn's disease, more ulcers, et cetera, that really is routinely part of practice. And I would even gather to say there's data on ustekinumab as well for early escalation, utilizing therapeutic drug monitoring in those difficult-to-treat patients.
So I think this is something that is really important to keep in mind. And so we may be even looking at treatment data that potentially is even higher than what we're reporting. And it is important that these are both essentially anti-cytokine-based treatments. But we must know that potentially looking at the therapy from a treat-to-target standpoint, trials such as STARDUST for ustekinumab suggest that maybe the treat-to-target strategy isn't what it is. And so, the rapidity of induction of clinical remission may be slightly different. And so both drugs, while utilizing the maximal benefit of them, we probably have to take both of those things into account.
PracticeUpdate: How do you decide which therapy to give a patient?
Dr. Naik: I will work with the patients to shrink the knowing-doing gap these days. We'll work with the patient's insurance coverage, their ability to continue therapy for longer periods of time. And importantly, I think it's very important to consider their extra intestinal manifestations. Certainly, peripheral axial arthropathies, joint disease, if there's any anterior uveitis, any ocular problems, or dermatologic problems, I think that may potentially help guide us towards using adalimumab perhaps. But certainly in patients who may have a history of, potentially, psoriasis, ustekinumab is something you can potentially consider in that end.
Additional Info
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