Dr Irani reviews his presentation from the virtual AIBD regional meeting August 27 on positioning various therapies for inflammatory bowel diseases.

Malcolm Irani, MD, is an assistant professor with Houston Methodist Academic Institute-Weill Cornell in Houston, Texas.

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TRANSCRIPT:

Malcolm Irani:
Hi, I'm Malcolm Irani, assistant professor at Houston Methodist Hospital, and I just gave a talk on evidence-based approach to Positioning Therapies in IBD at our AIBD Regional Conference in Houston. And I would like to highlight a few key learning objectives and take home points for you from our discussion.

The first point is that when deciding on advanced therapies, there are several aspects of the decision-making process. You must take into account our patient's profile in regard to their age, pregnancy, history of malignancy, their disease activity, as well as their disease severity, which is a more longitudinal evaluation of their disease, and includes things like previous steroid use, history of fistulas or abscesses and extraintestinal manifestations. And finally, safety is of utmost importance, especially in regards to infections, malignancy, and major adverse cardiovascular events. With that in mind, it's important to properly identify the patients who would best benefit from advanced therapies, and for that, we need to properly categorize the patients into mild, moderate, and severe disease.

For Crohn's disease, high-risk disease features include deep ulcerations, history of fistulas or perianal disease, as well as elevated CRP. For ulcerative colitis, considerations include extensive colitis history of CMV or C. difficile infection, elevated sedimentation rate, CRP and low albumin. We know that early advanced therapies for moderate to severe patients result in better longterm outcomes and low rates of complications.

For the anti TNFs, although there are no direct head-to-head trials, there are data to suggest that infliximab may be superior to adalimumab for induction of emission. Studies have also shown that when you combine a TNF with an immunomodulator combination therapy was superior to monotherapy. However, post hoc analysis of this data shows that this benefit may be primarily driven by adequate drug levels. This suggests that if you start with a combination therapy, you may be able to withdraw the immunomodulator if therapeutic levels are achieved, or that you may be able to use therapeutic drug monitoring to achieve a target level of remission.

The Varsity trial, which compared vedolizumab to adalimumab in bionaive patients with ulcerative colitis, was our first head-to-head trial for biologic therapies. At week 52, vedolizumab had higher rates of clinical remission and endoscopic improvement, the lower rates of steroid free remission. This data must be interpreted with caution, as there were no dosage adjustments or therapeutic drug monitoring between groups. However, what we can take away from this is that vedolizumab may be a strong first line agent for our patients with ulcerative colitis.

When exploring Ustekinumab and the JAK inhibitors, tofacitinib and pacritinib, it's important to note that both have been shown to be efficacious in the anti TNF failure population. In regards to the JAK inhibitors, we must remember that they're currently only approved in the anti TNF failure population. In addition, they have a black box warning for major adverse cardiovascular events and venous thromboembolism. However, this data was extrapolated from a cohort of patients with rheumatoid arthritis that were over the age of 50 and had at least one cardiovascular risk factor, which is not our typical UC patient.

Another small molecule to market that has shown efficacy as a first line agent is ozanimod. Its main adverse events are in relation to macular edema and bradycardia, so it is important to have an evaluation by an ophthalmologist prior to starting this concern for ocular symptoms.

When it comes to Crohn's disease, it's important to review CD trial, which is our first randomized control trial in Crohn's disease and compares ustekinumab to adalimumab in patients with moderate to severe Crohn's disease. And what we found was that at week 52, there is no difference between the two groups in terms of clinical remission and endoscopic remission and corticosteroid for remission. What we can take away from this is that ustekinumab has similar efficacy to adalimumab with better safety profile. In addition to our anti TNFs, ustekinumab and mepolizumab, we also have a new anti P19 inhibitor risankizumab, which is selected to IL23 and was approved for the treatment of Crohn's disease. There's data to suggest that the anti TNFs, ustekinumab, and mepolizumab are all effective for the treatment of perianal and visualizing Crohn's disease. When it comes to pregnancy, it is important to remember that none of the small molecule therapies have been studied in this patient population. We look forward to more data from the Piano Registry.

The last second point is that positioning of advanced therapies should be based on an individual assessment of the patient. At the end of the day, the best therapy for your patient is the one that your patient will take, feel comfortable with and has efficacy for the disease for which it is treating.

Thank you all and I hope to see you at AIBD in the future.

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