Christina Ha, MD, on Using Comparative Effectiveness Data in Treating Ulcerative Colitis

Positioning and sequencing decisions about therapies for ulcerative colitis (UC) “should be patient-centric, including clinical characteristics, and informed by shared decision-making,” Christina Ha, MD, stated in her presentation on comparative effectiveness and positioning therapies in ulcerative colitis at the Advances in Inflammatory Bowel Diseases regional meeting July 19 in Chicago, Illinois.

Dr Ha is director of the inflammatory bowel disease program at Mayo Clinic-Arizona in Scottsdale, Arizona.

Beginning with the approval of the Janus kinase (JAK) inhibitor tofacitinib in 2018, “there has been an explosion of therapeutic options for UC in recent years,” Dr Ha stated. In addition to the tumor necrosis factor (TNF) inhibitors, clinicians now have the ability to prescribe the interleukin (IL)-12/23 inhibitor ustekinumab, the sphingosine 1-phosphate (S1P) receptor modulators ozanimod and etrasimod, JAK inhibitor upadacitinib, the IL-23 inhibitor mirizikumab, and subcutaneous infliximab.

To help clinicians sort out the best options for their patients with ulcerative colitis for both effectiveness and safety, network meta-analyses of the numerous randomized clinical trials are useful, Dr Ha noted. Such analyses have shown, to date, that for inducing clinical remission in UC among biologic-naïve patients, the best options appear to be infliximab and vedolizumab; for patients previously exposed to anti-TNFs, tofacitinib and ustekinumab are superior to vedolizumab for induction of remission.

To maintain remission, no difference has been found among anti-TNF agents, vedolizumab, ustekinumab, or tofacitinib. The lowest risk of adverse events or infection are found with vedolizumab and ustekinumab.

In ulcerative colitis, the safety pyramid is topped by vedolizumab and the anti-IL-12/23 and IL-23 agents, followed by S1Ps, JAK inhibitors, anti-TNFs, thiopurines, the combination of anti-TNFs and thiopurines, with corticosteroids deemed the least safety therapy.

She reviewed a number of studies reviewing the safety of various agents, noting that the ORAL surveillance study of tofacitinib in rheumatoid arthritis resulted in a black-box warning from the US Food and Drug Administration regarding possible risks of serious cardiac events. To date, however, the same risks have not appeared among patients with UC treated with JAK inhibitors. The S1Ps have been associated with some risk of serious infections, bradycardia, and elevated liver enzymes.

Vedolizumab, an anti-integrin, is a gut-specific therapy with a low infection risk limited to nonserious URI symptoms and no specific malignancy risks. Ustekinumab, similarly, has demonstrated no serious risks of infection or malignancy.

Mirikizumab and risankizumab, monoclonal antibodies that bind to the p19 subunit of IL-23, have demonstrated a favorable safety profile compared to placebo in clinical trials, with some opportunistic infections and cancers in a small number of patients.

As with Crohn’s disease, the least safe option is inadequate treatment, Dr Ha stated. When choosing therapy, the clinician must consider the individual characteristics of the patient, including comorbidities, age, and preferences, as well as disease behavior, severity, complications, extraintestinal manifestations, and particularly success or failure of previous treatments. Pharmacokinetics, rapidity of onset, combination or monotherapy, and other factors also must be considered when choosing and positioning a therapeutic agent.

“Consider the efficacy-safety relationship to avoid longstanding corticosteroid use or the use of less effective agents in biologic-exposed populations,” Dr Ha concluded. “These choices must be informed by shared decision-making with the patient. And most of all, remember that the safest agent is the one that best controls the disease.

Patient context is essential, Dr Ha said. “There’s this idea that we have to prioritize safety over effectiveness with older patients,” she noted. “Safety doesn’t matter if it’s not effective. The safest treatment is often the treatment that effectively controls ulcerative colitis.”