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Commentary: Managing UC

CE / CME

Putting Patients First in Moderate to Severe Ulcerative Colitis

Physicians: maximum of 0.25 AMA PRA Category 1 CreditTM

Nurses: 0.25 Nursing contact hour

Released: December 14, 2020

Expiration: December 13, 2021

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As clinicians, we understand that there is never a good time to be a patient with ulcerative colitis (UC). However, we now have more effective and safe therapeutic options than ever. The challenge has become: Which medicine is optimal for a given patient, and how do we choose? Is a steroid taper best, with transition to a thiopurine? (This strategy is no longer very popular.) What about a biologic, and if so, which one?

Unfortunately, we have few comparative efficacy studies to guide us. Network meta-analyses and retrospective studies do offer some guidance, but we still lack the kind of robust evidence we need.

In thinking about medical therapy for UC, one of the key shifts has been away from solitary assessment of current symptomology toward the supplementary evaluation of overall inflammatory burden and risk factors for future colectomy. We now recognize that even in someone with less severe symptoms, substantial inflammation or numerous risk factors for colectomy may warrant consideration of early initiation of more effective treatment.

With all of this in mind, a panel of my colleagues and I recently launched an interactive decision support tool, in which anyone can enter specific patient characteristics and instantly receive our expert recommendations for management of moderate to severe UC. I invite you to try it here.

The experience of creating this tool focused the five of us, as providers who predominantly see patients with Crohn disease or UC, on the thought processes underpinning our treatment decisions.

The prevailing messages among us were that, in the less ill outpatient, we pick the safest therapies first, namely ustekinumab and vedolizumab. In particular, when those patients are of advanced age or have comorbid medical conditions, we are even more likely to select those agents.

And for patients with more severe disease, our go-to options change to infliximab or tofacitinib; this willingness to use tofacitinib makes sense because emerging safety data for this agent seem reassuring.

Beyond these comparatively clear-cut scenarios, other management subtleties exist. For instance, in patients with extraintestinal symptoms, there is a clear shift away from vedolizumab toward agents that are not gut selective (ie, infliximab or tofacitinib, possibly ustekinumab).

Among women of childbearing age, we have really good safety data except with tofacitinib. Network meta-analyses of first-line and second-line pharmacotherapies reinforce that the preferred treatment options for pregnant women with moderate to severe UC include azathioprine, TNF inhibitors, ustekinumab, and vedolizumab. Because there are currently limited human data on the use of tofacitinib during pregnancy, other options should be considered in this population, particularly during the first trimester.

And in someone without commercial insurance, we need to think about which drugs are billed under the medical benefit as opposed to the pharmacy benefit. Ultimately, the payer will influence drug selection, particularly for biologic‑naive patients.

Putting Patients First
As time progresses, additional therapies will inevitably be approved and will make drug selection even more challenging. What we really need are precision medicine diagnostics that tell us exactly what drug is best for each patient. What buccal swab, blood test, or pinch biopsy will allow us to zero in on the right choice? Those methodologies are still awaited and would be particularly useful for nonspecialist providers.

Until then, the process of shared decision-making will be critical. It is our duty as providers to lay out all of the options, give accurate information, and assist patients in choosing. With my patients, I discuss the available head-to-head data, for example showing—at least in one trial—improved clinical remission and mucosal healing with vedolizumab vs adalimumab.

Then I look at how risk averse the individual is. Some patients want to get better quickly and are subsequently willing to tolerate more risk. Others are quite nervous, so we go over safety in more depth.

If a patient is very sick, he or she cannot wait 4-6 weeks to feel better. That may prompt discussion of a steroid bridge to one of the slower onset of action agents compared with immediate initiation of infliximab or tofacitinib.

Finally, I discuss mode of administration to ascertain whether someone is comfortable with self-injection or if he or she might prefer a daily pill or visit to an infusion center.

Sometimes making this choice is overwhelming for patients when multiple options need to be weighed. In these cases, a decision support tool may help focus the conversation on a reduced set of options and mitigate some of that stress.

Cycling and Cure
I would also note that just because we have more options available, giving another medical therapy might not be the right thing to do. With every drug you try, there is a chance that a deep remission may be achieved. However, we must also remember that colectomy is a cure. It is admittedly a cure with consequences, but I can count on one hand the number of patients who have told me they regret having a colectomy for UC. Most people delay colectomy far too long and are very happy once it is all said and done because they feel so much better.

One of my favorite such encounters was with a woman in her 60s. I asked her, “Are you having any problems with intimacy now that you have an ileostomy?” Her face brightened and she said, “Gosh no. I’m having sex more than ever. I feel so much better. The ileostomy’s not keeping me from having sex. My diarrhea, fatigue, and urgency were keeping me from having sex.”

Of course, sex is merely one metric but speaks to how quality of life is important. Sometimes surgical options are appropriate, even if all drug options have not been exhausted. At every step, if the medicine fails, we owe it to our patients with UC to revisit the available treatment options, including surgery.

How are you managing patients with moderate to severe UC? Join the discussion by sharing your experiences in the comments box or by answering the polling question. And, again, I invite you to give our decision support tool a try here.

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In a biologic-naive outpatient with moderate UC, which of the following agents would you recommend?
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