Background & Objectives
Psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic immune-mediated inflammatory disorders that can significantly alter an individual’s quality of life. Although there is no cure for these conditions, insights about their pathogenesis have led to the development of cytokine-based therapies that have revolutionized disease management.
The interleukin (IL) 23/Th17 immune axis plays a crucial role in the pathogenesis of both psoriasis and PsA/AS, and interest in targeting this pathway for treatment is growing. Epidemiology studies have established strong associations between psoriasis/PsA/AS and inflammatory bowel disease (IBD), with an increased risk of Crohn’s disease and ulcerative colitis in patients with psoriasis and PsA/AS, and an increased risk of psoriasis and PsA/AS in patients with CD or UC.
IBD occurs in 1% of patients with psoriasis, which is approximately four times more frequent than in the general population, with the highest risk occurring in patients with PsA/AS. Psoriasis and PsA/AS share common genetic susceptibility loci and pathologic mechanisms with IBD, including several immune-signaling and cytokine pathways. Drugs approved to manage psoriasis/PsA/AS and IBD include anti-tumor necrosis factor (anti-TNF) agents and anti-IL-12/IL-23 antibody therapies.
The immune pathways of psoriasis and IBD also share the IL-23/Th17 axis. However, IL-17 inhibitor treatments have been reported to exacerbate or trigger new-onset IBD in patients with psoriasis. Additionally, clinical trials of IL-17 inhibitors in IBD were unsuccessful and terminated early due to worse clinical outcomes with IL-17 inhibitors than with placebo.
The purpose of this study was to investigate whether treatment with an IL-17 inhibitor was associated with a higher risk of IBD in a large clinical population of patients with psoriasis and PsA/AS, compared with a similar patient population treated with apremilast, a phosphodiesterase 4 (PDE4) inhibitor, or etanercept, a TNF inhibitor.
Methods
This nationwide cohort study involved the French National Health Data System database. All adult patients with psoriasis and PsA/AS who were identified as having newly initiated treatment with an IL-17 inhibitor during 2016–2019 were included. For control purposes, patients with psoriasis and PsA/AS who had newly initiated either 1) apremilast or 2) etanercept during this period but had not received an IL-17 inhibitor were included. The follow-up end date was Sept. 30, 2019. The primary end point was the risk of occurrence of IBD associated with exposure to an IL-17 inhibitor compared with exposure to the other treatments.
Results
The study by Penso et al. included a total of 16,793 new IL-17 inhibitor users (mean±SD age 48.4±13 years; 46% men), 20,556 new apremilast users (age 52.5±14.6 years; 53% men) and 10,245 new etanercept users (age 46.3±15 years; 44% men). Previous systemic treatments were more similar in their mechanisms of action to IL-17 inhibitors and etanercept than to apremilast.
IBD occurred in 132 patients: 72 new IL-17 inhibitor users (0.43%), 11 new apremilast users (0.05%) and 49 new etanercept users (0.48%). Most IBD cases occurred after six months of exposure (82%, 55% and 76%, respectively). After propensity score weighting, the risk of IBD was significantly greater among patients initiating an IL-17 inhibitor than among those initiating apremilast (weighted hazard ratio [HR] 3.8 [95% confidence interval (95% CI) 2.1–6.8]). No difference in the risk of IBD between new IL-17 inhibitor users and new etanercept users was observed (weighted HR 0.8 [95% CI 0.5–1.2]).
Conclusion
Although the results need to be confirmed in other large studies, the researchers found that patients with psoriasis and PsA/AS treated with an IL-17 inhibitor do not have a higher risk of developing IBD than patients with the same severity of underlying disease treated with etanercept.
For full study details, including source material, refer to the full article.
Excerpted and adapted from:
Penso L, Bergqvist C, Meyer A, et al. Risk of inflammatory bowel disease in patients with psoriasis and psoriatic arthritis/ankylosing spondylitis initiating interleukin-17 inhibitors: A nationwide population-based study using the French national health data system. Arthritis Rheumatol. 2022 Feb;74(2): 244–252.
