Assessment of inflammatory bowel disease risk prior to commencing IL-17 inhibitors: A cross sectional analysis of Irish practice

Abstract

Dermatologists are well-acquainted with the transformative impact of biologics in managing chronic skin conditions such as psoriasis and hidradenitis suppurativa (HS). This success is mirrored in the field of rheumatology. Interleukin (IL)-17, a proinflammatory cytokine, plays a crucial role in host defence but paradoxically can contribute to the pathogenesis of inflammatory diseases. IL-17 inhibition has been linked to the unmasking or exacerbation of inflammatory bowel disease (IBD) in some patients.¹ Despite this, there are currently no guidelines for IBD screening before initiating IL-17 inhibitors.

This study aimed to evaluate current practices among Irish dermatologists and rheumatologists in assessing IBD risk before commencing IL-17-targeted treatments. An anonymous survey was disseminated to members of the Irish Association of Dermatologists and the Irish Society of Rheumatology in March 2024.

Sixty-five consultants and registrars responded (68% dermatology, 32% rheumatology), with 54% at consultant level. A significant majority (97%) were aware of an association between Il-17 inhibitors and IBD unmasking (Figure 1). Routine assessment for IBD risk before initiating IL-17 therapy was performed by 87% of dermatologists and 76% of rheumatologists. Faecal calprotectin measurements were used routinely by 8% of clinicians (11% dermatology, 0% rheumatology), but were more frequently considered when patients had gastrointestinal (GI) symptoms or positive family history, with 73% of clinicians (92% dermatology, 76% rheumatology) opting for the test in these cases. At follow-up, 57% of respondents in both specialties were assessed for GI symptoms in patients on IL-17 inhibitors.

In the absence of formal screening protocols, this survey offers valuable insights into current practices, highlighting the variability in how Irish clinicians assess IBD risk before and during IL-17 inhibitor treatment. Faecal calprotectin, a simple and inexpensive test (€7–€20 in Ireland), has high sensitivity and specificity for detecting IBD in patients with GI symptoms, but its role in asymptomatic patients remains undetermined. Our survey found that faecal calprotectin was primarily used in patients with GI symptoms or risk factors, rather than as a universal screening tool, which may be appropriate given the low risk of developing IBD with anti-IL-17 therapy. A thorough risk-benefit analysis could help determine whether universal or targeted screening based on risk factors is necessary and cost-effective. Generally, a faecal calprotectin level above 200 µg/g is indicative of bowel pathology, while values below 50 µg/g are considered negative, though no specific concentration can definitively rule out IBD.² Additional research is needed to determine the thresholds at which IL-17 inhibitors are considered safe. There was discordance in how consistently symptom screening was applied, despite widespread awareness of IBD risks, as 57% of respondents reported monitoring for GI symptoms during follow-up. The risk of IBD onset is believed to be highest during the first 3 months of treatment, but the need for ongoing monitoring beyond this period needs to be clarified.¹

Psoriasis and HS are associated with many comorbidities, including cardiovascular disease, metabolic syndrome, spondyloarthropathies and IBD.^{3, 4} Patients with psoriasis have a 1.7-fold increased risk of ulcerative colitis or Crohn disease compared to controls,⁵ and patients with HS have a 3.4-fold increased risk.⁶ For those with a pre-existing IBD diagnosis, there is a strong recommendation to avoid IL-17 inhibitors in favour of biologics targeting different pathways. Given the profound impact that IBD can have on patients' quality of life and the potential for anti-IL-17 agents to unmask this condition, it is essential to assess patients for IBD risk before initiating treatment. Establishing a clear and standardised screening protocol will help ensure safer and more effective use of these therapies in clinical practice.

By continuing to evaluate and refine our practices, we can better mitigate the risks associated with IL-17 inhibition and ensure that patients with both dermatologic and GI challenges receive comprehensive, safe and effective care.

Amy Long: Conceptualisation; methods; writing—original draft. Claire Quigley: Writing—review and editing. Lisa Murphy: Writing—review and editing. Susan O'Gorman. Writing—review and editing.

The authors declare no conflict of interest.

Not applicable.