Biologic Choice May Affect Perianal Crohn’s Disease Outcomes Biologic Choice May Affect Perianal Crohn’s Disease Outcomes

Choice of biologic therapy in the first line and later may impact long-term outcomes in patients with perianal Crohn’s disease (pCD), according to a retrospective study.

Dr John Gubatan

John Gubatan, MD, of Stanford (Calif.) University, and colleagues reported that, compared with no biologic therapy, first-line treatment with an anti–tumor necrosis factor (TNF) agent or ustekinumab significantly reduced risk of perianal abscess recurrence at 5 years, whereas vedolizumab offered no such benefit. After failure of the initial anti-TNF, switching to another anti-TNF agent is the most effective option.

“Although pCD is recognized to be an aggressive phenotype, data on whether escalating to a biologic at the time of perianal disease diagnosis may alter the natural history and long-term clinical outcomes of pCD is limited,” the researchers wrote in Journal of Clinical Gastroenterology. “This is the first study to explore how the type of biologic therapy at the time of perianal disease diagnosis and change in biologic therapy after first anti-TNF failure are associated with rates of long-term clinical outcomes.”

The study included 311 patients with pCD treated at Stanford University from 1998 to 2020. At the time of diagnosis, 168 of these patients started a biologic, most often an anti-TNF agent (n = 138), followed distantly by ustekinumab (n = 16) or vedolizumab (n = 14). Efficacy of these first-line biologics was compared with no biologic therapy in terms of five clinical outcomes at 5 years: surgical intervention, colectomy, permanent diversion, fistula closure, and perianal abscess recurrence.

Although both reduced risk of perianal abscess recurrence, it was still higher with anti-TNF therapy (hazard ratio, 0.48; 95% confidence interval, 0.32-0.74) than with ustekinumab (HR, 0.20; 95% CI, 0.07-0.56). Ustekinumab also increased the rate of perianal fistula closure by more than threefold (HR, 3.58; 95% CI, 1.04-12.35).

Vedolizumab, on the other hand, offered no significant benefit across any of the five outcomes.

None of the biologics had an impact on rates of surgical intervention, colectomy, or permanent diversion.

Further analyses explored the long-term effects of second-line biologic choice after initial failure with anti-TNF therapy. Switching to another anti-TNF agent was more effective than switching to ustekinumab at reducing risks of colectomy (HR, 0.20; 95% CI, 0.04-0.90) and permanent diversion (HR, 0.16; 95% CI, 0.03-0.94); switching to ustekinumab was more effective than switching to vedolizumab for perianal fistula closure (HR, 0.22; 95% CI, 0.05-0.96).

Switching to another anti-TNF biologic or ustekinumab may be associated with better 5-year outcomes, compared with switching to vedolizumab in patients with pCD, according to Gubatan. Other guidelines or data that might steer this sequencing decision are scant. However, the findings should be validated with prospective data, ideally from head-to-head trials.

Dr Jordan Axelrad

Jordan E. Axelrad, MD, of NYU Langone Health, New York, said the present study is noteworthy for addressing a “very-difficult-to-treat condition that has limited data as well as very limited long-term outcome data for our currently available interventions.”

Axelrad appreciated how the study focused on the distribution of clinical manifestations of pCD, including ulcers (10%), fissures (23.2%), abscesses (76.1%), and fistulas (84.2%). According to Axelrad, the efficacy data provide really important insights for clinicians who choose biologic therapies. He noted that, in the absence of head-to-head clinical trials, “it’s absolutely important that we use these results to help us guide therapy” for patients with pCD.

While the biologics included in the study were efficacious to varying degrees, Axelrad pointed out that no choice was associated with a reduced risk of surgical intervention. “That really underscored for me how complex this patient population is,” he said. “Despite good medical therapies … we’re still not necessarily making a huge dent in the risk of surgical intervention requirements for this complex patient group.”

Gubatan disclosed support from a Chan Zuckerberg Biohub Physician Scientist Scholar Award, a National Institutes of Health NIDDK LRP Award, and a Doris Duke Physician Scientist Fellowship Award; his colleagues reported no conflicts of interest. Axelrad reports relationships with Janssen, AbbVie, Pfizer, and others.

This article originally appeared on, part of the Medscape Professional Network.