IL-17 Inhibitors Not Linked to IBD Risk in Patients with Immune Disorders

A new nationwide cohort study from the Paris-East Créteil University in France concluded that patients with psoriasis, psoriatic arthritis or ankylosing spondylitis did not experience a higher risk of inflammatory bowel disease (IBD) when treated with interleukin 17 (IL-17) inhibitors.

The 3 chronic immune-mediated disorders have greatly impacted the quality of life of patients throughout the years, and while no cure exists, medical professionals have urged for a variety of ways to manage the severity of the conditions such as being cytokine-based therapies.

Emilie Sbidian, MD, and investigators noted that IL-17 inhibitors have played a crucial role in the pathogenesis of these immune-mediated disorders.

Commercial IL-17 inhibitors such as secukinumab, ixekizumab, and brodalumab, are considered some of the highest efficacious biologics for moderate-to-severe of psiorasis, psoriatic arthritis and ankylosing spondylitis.

However, recent epidemiological studies have established associations between these disorders and inflammatory bowel disease (IBD) in addition to an increase of Crohn’s disease (CD) and ulcerative colitis (UC).

The investigators noted that inflammatory bowel syndrome occurs approximately 4 times more in patients with psoriasis than the general population.

Additionally, studies reported that IL-17 treatment had exacerbated or triggered new-onset IBD in patients with psoriasis, and early clinical trials of IL-17 were halted and terminated after data showed that patients received worse clinical outcomes than those in the placebo group.

Despite this, information from the previous studies was limited.

This prompted Sbidian and fellow investigators to investigate if IL-17 inhibition was truly associated with a higher risk of IBD in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis.

The Methods

The investigative team pulled administrative data from a French national health data system that covered approximately 99% of the French population and had been used in several pharmacoepidemiologic studies in the past.

In addition to the database, the researchers assembled a study population of 47,643 patients with psoriasis, psoriatic arthritis, and ankylosing spondylitis with at least 1 prescription of an IL-17 inhibitor. All adults 18 years or older were eligible to apply between July 2016 and May 2019.

Prescriptions for apremilast or enranercept were considered for the study, and a non-exposed etanercept cohort was established. Researchers also studied 16,793 etanercept-naïve patients, otherwise defined as “new users,” who were included in the study population.

The covariates established at baseline were age, sex, and comorbidities such as chronic obstructive pulmonary disease (COPD), cancer, hypertension, etc.

Follow-ups with patients regarding an IBD event, death from any cause, systemic treatment switches, or losses due to follow-up were done before September 30, 2019.

The Findings

Researchers found that patients who had initiated an IL-17 or etanercept therapy, many of whom were younger women, experienced lower proportions of comorbidities than apremilast new-users.

Additionally, 72 (.43%) new cases of IBD were identified in the IL-17 new-users group, as well as 11 (0.05%) in apremalist new-users and 49 (0.48%) in etanercept new-users groups.

Overall, risk of IBD was significantly higher in patients exposed to IL-17 than any other group. These patients were 4 times more likely to develop CD than apremilast new-users and 2 times more likely to develop UC, despite the latter showing no statistical significance.

The study also showed that among patients with psoriasis, IL-17 inhibitors new-users were 8 times as likely to develop IBD than apremalist new-users. No differences were shown for the 2 other disorders.

Overall, while the investigators noted that the risk of IBD was greater in the IL-17 inhibitors group when compared to the apremalist groups, they observed no difference between IL-17 inhibitors and etanercept new-users.

When etanercept was used as a comparator, treatment with IL-17 was not associated with a higher risk of IBD. Additionally, Sbidian and colleagues hypothesized the severity of the underlying disease in patients could explain the difference in the 2 comparators.

They believed further research was required to fully confirm their findings.

“We herein demonstrated that treatment with IL17 (inhibition) is not associated with a higher risk of IBD in patients with psoriasis, psoriatic arthritis or ankylosing spondylitis when taking into account the severity of the underlying disease when using etanercept as a comparator,” the team said. “These results need to be confirmed in other large databases.”

The study, “Risk of inflammatory bowel disease in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis initiating interleukin 17 inhibitors: a nationwide population-based study using the French national health data system,” was published online in Arthritis & Rheumatology.