Vedolizumab Tied to Lower Risk for Serious Infections in Ulcerative Colitis

Vedolizumab (Entyvio) treatment was linked with a lower risk of some infections compared with tumor necrosis factor (TNF) antagonists in patients with ulcerative colitis (UC), researchers reported.

An observational study of health insurance claims found a 46% lower risk of serious infections requiring hospitalization in UC patients given the integrin 4β7-targeting antibody, according to Siddharth Singh, MD, of the University of California San Diego, and colleagues.

Vedolizumab was associated with a reduced hazard ratio of 0.54 (95% CI 0.35-0.83) versus anti-TNF, they reported in Clinical Gastroenterology and Hepatology.

However, there were no significant differences observed for such infections in Crohn’s disease (CD) for an HR of 1.30 (95% CI 0.80-2.11), the authors stated. In addition, the antibody was associated with a higher risk of serious IBD-related GI infections, particularly in CD patients.

The overall risk of serious infections in patients with any type of inflammatory bowel diseases (IBD) treated with vedolizumab versus anti-TNF was 0.70 (95% C I0.56-1.13).

The safety of vedolizumab in UC may be driven by a lower risk of extra-intestinal infections that are not directly related to underlying IBD activity, Singh’s group suggested.

The study cohort included 4,881 new users of anti-TNF and 1,106 new users of vedolizumab who were identified in a retrospective analysis of medical and pharmacy administrative claims from the OptumLabs Data Warehouse.

All patients, ages 18 to 89, filled a prescription (or received an infusion) for TNF antagonists — infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), and/or golimumab (Simponi; Simponi ARIA) — and/or vedolizumab in the period Jan. 1, 2014, to Dec. 31, 2018.

The mean age of anti-TNF recipients was 41, 50.8% were male, and 60% had CD. In this group, 434 developed serious infections over 5,786 person-years of follow-up.

In vedolizumab recipients, 39% of whom had CD, the mean age was 44, 49.3% were male, and 86 developed serious infections over 1,040 person-years of follow-up.

By race, slightly more than 70% of all patients were white, and those treated with anti-TNF had a lower burden of comorbidities.

Besides infectious complications related to penetrating and/or perianal CD, Clostridioides difficile colitis was the most common GI infection.

After initiating biologic therapy, 435 anti-TNF and 85 vedolizumab recipients developed some infection requiring hospitalization, corresponding to an incidence rate of 5.6 (95% CI 5.0-6.2) and 5.5 (95% CI 4.3-7.1) per 100-person-years, respectively.

The most common serious infections were:

• Sepsis: 205 with anti- TNF vs 39 with vedolizumab
• GI infections: 136 vs 36
• Pulmonary infections: 128 vs 25

In the two treatment groups, 54 anti-TNFa and 13 vedolizumab recipients experienced opportunistic infections requiring hospitalization, corresponding to an IR of 0.7 (95% CI 0.5-0.9) and 0.7 (95% CI 0.3-1.4), per 100 person-years’ exposure, respectively.

The incidence rate ratios of serious infections for vedolizumab versus TNF antagonists for all IBD patients were:

• IBD: IRR 0.99 (95% CI 0.74-1.31)
• CD: IRR 1.40 (95% CI 0.90-2.09)
• UC: IRR 0.70 (95% CI 0.46-1.05)

No specific differences were observed in the comparative safety of vedolizumab versus TNF antagonists in older IBD patients who may be at higher risk of serious infections with immunosuppressive therapy, according to the authors.

Miguel Regueiro, MD, of the Cleveland Clinic in Ohio, told MedPage Today, that the current findings will have no impact on his practice “as I have been using vedolizumab earlier as first-line therapy in my ulcerative colitis patients.”

However, “the fact that the safety appears higher in the UC patients is reassuring and supports this first-line use. I also think that many physicians are using vedolizumab earlier and the study may add to the assurance everyone has around the safety of vedolizumab,” said Regueiro, who was not involved in the study.

He added that “one caveat to note upfront is that this is a retrospective claims database study, which may not reflect clinical practice. And one question that remains from the study: Are IBD severity, phenotypes, and disease behavior different between vedolizumab and anti-TNF patients? This has implications in that a more severe IBD patient may also be prone to infections.”

Researchers at Brigham and Women’s Hospital in Boston similarly reported that while the risk of serious infections associated with vedolizumab was not different compared with anti-TNF in the overall group of patients with IBD, the risk varied according to IBD subtype, decreasing in patients with UC, but not CD.

Limitations to the administrative database study included the lack of data on measures of disease activity, endoscopy reports, and details of disease location and behavior. Unobserved confounders may have been present, especially those due to treatment selection, Singh and colleagues noted, and they were unable to compare the risk of serious infections with TNF antagonist or vedolizumab monotherapy alone against combination therapy with immunomodulators.

Finally, because of the low event rate, Singh’s group was not able to examine the risk of all opportunistic infections so they focused on those requiring hospitalization.

They called for prospective registry and real-world observational studies to confirm their findings, and to contextualize risk of serious infections with other non-TNF antagonists, such as ustekinumab (Stelara), as well as janus kinase inhibitors, such as tofacitinib (Xeljanz).

“The interplay of effectiveness and relative safety of different agents, in patients who respond vs. do not respond to therapy also merits close evaluation to understand risk-benefit trade-offs of novel therapies,” the authors wrote, adding that the findings will aid the optimal selection of biologics according to a patient’s risk of disease- and treatment-related complications.