Positioning Advanced Therapies in Ulcerative Colitis

When selecting the right therapy for ulcerative colitis (UC), regardless of disease location or patient age, disease activity and severity may be the most important factors to consider, along with patient buy-in​, said Angelina Collins, MSN, ANP-BC, in her presentation to the APP Inflammatory Bowel Disease Institute virtual meeting.

“How do we think about mild disease vs not mild? I think this is the right place to start because sometimes we struggle with moving patients on from therapies used for mild disease to more advanced therapy,” Collins said.

She described mild UC as defined by Mayo score​, beginning with the number of stools per day. Mild disease defined by Mayo score includes stool frequency of 1 to 2, which represents 1 to 4 stools what is their normal, is Collins explained. “It’s really important to know what’s normal or baseline for the patient because then we can get an idea of how severe their disease is.”

A rectal bleeding score of 1 means there is visible blood less than 50% of the time and no blood separate from stool in order to be considered mild. “Automatically, if there is blood separate from stool, that’s a Mayo 3 and considered severe rectal bleeding, “ she explained. A Mayo endoscopic subscore of 1, indicating erythema and a decreased vascular pattern without friability, also qualifies as a measure of mild disease.

“Anything beyond this is NOT mild disease,” Collins emphasized. Other indicators of “beyond mild” include the need for prednisone without being able to taper without a relapse of symptoms. She urged the attendees to keep track of their patients’ prednisone prescriptions. “Did your patients need another prescription within 3 months of the last? More than 1 prednisone prescription in a year? If so, it’s time to move on from steroids.”

Collins noted that in considering other therapies for patients, to keep in mind that the patient should not have to fail an immunomodulator or have extensive or pancolitis to before moving to advanced therapy. “All of us have seen in our practices patients with only proctitis, but that should be enough. A therapy for mild disease may not be effective here.”

“To really understand and select therapy,” she said, the clinician needs to begin with assessing disease activity. “How sick is your patient now? What is the appearance on endoscopy? What about prognostic factors? Is the patient at low or high risk for surgery or disease complications? We really want to combine disease severity and disease activity to really understand and select the right therapy.”

It's also important to take into consideration extraintestinal manifestations and comorbidities, Collins stated. “This helps us to think about how to care for the patient holistically.”

“The conversation about safety and efficacy I find very interesting,” she continued. “I would challenge us to think about efficacy as being one of the most important factors here. We understand that uncontrolled or untreated disease are the primary factors for future complications. By controlling the disease we’re doing a better job of keeping our patients healthier, getting them into remission, where they feel well and have healing; it’s a safer scenario and will yield better outcomes in the long run.”

When choosing a medication for a patient who has been exposed to has been previously exposed to an advanced therapy, Collins stated, it is important to determine whether the patient was intolerant to the medication and thus discontinued it, or whether they never had any improvement at all, which is primary nonresponse. A secondary loss of response occurs when the patient sees some improvement but then fails to sustain that or progress. “With the anti-TNFs, you want to check drug concentration levels in cases of secondary loss of response,” she said.

Mode of administration can be very important for patients who do not near an infusion center or a lab for monitoring or may have needle phobia, Collins added. Insurance authorization and cost are “really important factors,” as well, she said.

Ultimately, she said, “Medication doesn’t work if the patient won’t take it. You really must have buy-in from your patient for the choice of therapy.”

How do you actually make the choice of therapy? Collins reviewed sources of data that can help the clinician make the best choice. Randomized clinical trials can be the most robust, she explained, with head-to-head studies that compare two or more therapies also providing excellent data. She referenced the VARSITY trial that compared vedolizumab to adalimumab among patients with Mayo scores of 2 or 3; 21% had failed anti-TNFs. In this study vedolizumab proved superior to adalimumab

Observational studies—sometimes called real-world analyses—also can provide guidance. Collins reviewed results of studies comparing Janus kinase inhibitors as well as others that compared infliximab to vedolizumab, showing how the results can help clinicians make decisions on therapies for their patients.

Clinical guidelines also provide important sources of information to help guide decisions about therapies for UC. Collins reviewed the recent update of clinical guidelines for ulcerative colitis developed by the American College of Gastroenterology, which advise against using thiopurine or methotrexate monotherapy, but support the use of an immunomodulator with infliximab. Anti-TNFs, JAK inhibitors, IL-23s, vedolizumab and S1Ps are all approved for induction of remission in these guidelines, she noted.

The guidelines also support the use of advanced therapy for patients with proctitis. Vedolizumab is recommended over adalimumab, based on the results of the VARSITY trial. Among nonresponders to anti-TNFs, when the patient has adequate drug concentrations, the guideline advises changing drug class, Collins related.

The American Gastroenterological Association released “living guidelines” in which data gleaned from network meta-analyses supports the early use of advanced therapy rather than gradual, step-up therapy. “This has been shown multiple times” to produce better outcomes, Collins stated.

The AGA guidelines also set out categories of therapies as higher efficacy, intermediate efficacy, and lower efficacy and further classifies medications based on whether the patient is naïve or previously exposed to an advanced therapy.

When choosing medications for patients with EIMs, Collins said, “My number one caveat, please make sure YOU are prescribing, to ensure the patient is receiving the GI dosing” when one drug is being used to treat both IBD and dermatologic or rheumatologic conditions.  

Collins further explored special populations and conditions that can affect the choice of IBD therapies, from previous serious infections to existing or former malignancy and organ transplantation. She advises coordination with other caregivers, such as oncologists and hepatologists, to choose the therapy that provides efficacy for IBD as well as respecting safety issues.

“Keep good medication history record to track therapy trials, responses, and failures, to guide future treatment selections​,” Collins concluded.