New UC guideline endorses early use of advanced therapies

The American Gastroenterological Association (AGA), in an update to its living practice guideline, recommends the early use of advanced therapies for the pharmacological management of moderate-to-severe ulcerative colitis (UC) in adult outpatients.

UC has a protracted, relapsing-remitting course, with up to 20 percent of patients requiring colectomy. At least 33 percent require hospitalization to manage the disease. [Clin Gastroenterol Hepatol 2018;16:343-356.e3] 

“Effective control of inflammatory activity in UC involves an informed approach to the selection of therapy,” said the guideline authors. “With the significant expansion in the therapeutic armamentarium for moderate-to-severe UC, an updated practice guideline should help guide treatment.”

The guideline defines moderate-to-severely active UC as having moderate-to-severe symptoms with a Mayo endoscopic score of 2 (presence of diffuse erythema, friability, erosions) or 3 (with spontaneous bleeding or ulcerations) or mild symptoms with a high burden of inflammation or poor prognostic features.

Positioning advanced therapies

The guideline suggests early use of advanced therapies and/or immunomodulator therapy rather than gradually stepping up treatment after failing 5-aminosalicylates (5-ASAs). [Gastroenterology 2024;167:1307-1343]

“Early use of advanced therapies, including biologics and small-molecule drugs are more effective than 5-ASAs or thiopurines and methotrexate for most patients with moderate-to-severe UC and those with poor prognostic factors,” said guideline co-author Dr Manasi Agrawal, gastroenterologist and assistant professor of medicine at Icahn School of Medicine at Mount Sinai, New York City, New York, US. “Individual patient factors such as age, comorbidities, frailty, pregnancy and adherence, as well as preferences, should be incorporated when selecting advanced therapies.”

The AGA recommends using any of the following over no treatment: infliximab, golimumab, vedolizumab, tofacitinib, upadacitinib, ustekinumab, ozanimod, etrasimod, risankizumab, or guselkumab. Adalimumab, filgotinib, or mirikizumab are likewise suggested over no treatment.

First-line therapy for advanced therapy-naïve patients

For adult outpatients who are naïve to advanced therapies, the AGA suggests using a higher-efficacy medication (infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, and guselkumab) or an intermediate-efficacy medication (golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab) rather than a lower-efficacy medication (adalimumab).

Patients with previous exposure to advanced therapies

In patients who have previously been exposed to ≥1 advanced therapy, particularly TNF-α antagonists, the AGA suggests using a higher-efficacy medication (tofacitinib, upadacitinib, and ustekinumab) or an intermediate-efficacy medication (filgotinib, mirikizumab, risankizumab, and guselkumab) rather than a lower-efficacy medication (adalimumab, vedolizumab, ozanimod, or etrasimod).

Immunomodulators

The AGA suggests against using thiopurine monotherapy to induce remission in adult outpatients with active disease. However, it suggests using thiopurine monotherapy, rather than no treatment, for maintaining remission typically induced with corticosteroids. Methotrexate monotherapy is not advised for inducing or maintaining remission.

Biologics plus immunomodulator

The guideline recommends combining TNF antagonists with immunomodulators rather than corresponding monotherapy. There was no recommendation in favour of or against using non-TNF antagonist biologics in combination with immunomodulators over non-TNF biologics monotherapy.

De-escalation therapy

For patients in corticosteroid-free remission for at least 6 months on combination therapy of TNF antagonists and an immunomodulator, the AGA suggests against withdrawing TNF antagonists. There was no recommendation for or against withdrawing immunomodulators or continuing combination therapy.

In patients who have failed 5-ASAs and have escalated to therapy with immunomodulators or advanced therapies, the AGA suggests stopping 5-ASAs.

The guideline also outlined implementation considerations for optimal use of these medications in different scenarios. “Key considerations include patient-related factors such as age, frailty, other health conditions, consideration for pregnancy, patient preferences, and access to healthcare,” said Agrawal. “Shared decision-making is likewise important when selecting the management strategy for moderate-to-severe UC.”

The guideline targets gastroenterologists, advanced practice providers (nurse practitioners or physician assistants), and primary care providers.

“We provide this practical guidance based on best-available evidence to make it easy for clinicians to make informed choices from the multiplicity of available treatments for UC,” added guideline co-author Dr Ashwin Ananthakrishnan, a gastroenterologist at Massachusetts General Hospital in Boston, Massachusetts, US.

However, the recommendations come with a caveat. “The guideline is meant to be broad recommendations for managing patients with moderate-to-severe UC and is not intended to address the intricacies of individual patients,” the authors said. “Provider experience and patient values and preferences can reasonably inform the selection of alternative treatment options.”

Knowledge gaps

Additionally, the authors identified several knowledge gaps that future studies should address. These include a paucity of head-to-head comparison trials, including active comparators, to accurately inform the positioning of different treatments and therapeutic mechanisms.  

Recognizing that novel therapeutic strategies may emerge in the coming years, such as a combination of advanced therapy or episodic use of nonimmunogenic agents, the authors said they would review the evidence every 6 months and update relevant recommendations to the guideline.