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You are here: Home / Articles / The Effects of IL-17A Inhibitors on the Microbiota

The Effects of IL-17A Inhibitors on the Microbiota

February 16, 2021 • By Vanessa Caceres

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Tracking Results

Patients in the IL-17 inhibitor cohort were older and more predominantly women than in the TNF inhibitor group. However, neither parameter reached statistical significance. The majority of patients had PsA. Nine subjects had psoriasis (64.3%) and were diagnosed with peripheral PsA (35.7%), axial PsA (7.1%), peripheral/axial PsA (28.6%) and axial SpA (21.4%). 

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In the TNF inhibitor cohort, all patients had psoriasis and either peripheral PsA (53.3%) or a combination of peripheral/axial PsA (46.7%). 

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About one-third of patients in each cohort had elevated C-reactive protein levels (28.6% in the IL-17 group, compared with 33.3% in the TNF inhibitor group).

The authors found an average expansion of Clostridiales and Erysipelotrichales and reduction of Bacteroidales in those with PsA and SpA compared with healthy subjects. They also found an average expansion of Clostridiales and reduction of Bacteroidales after TNF inhibitor therapy compared with baseline, and an average reduction of Clostridiales with concomitant expansion of Bacteroidales after IL-17 inhibitor therapy, compared with baseline. Prominent shifts in Clostridiales relative abundance were seen with IL-17 inhibitor therapy, which were less pronounced with TNF inhibitor therapy. 

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Treatment with an IL-17 inhibitor also was associated with a “robust expansion” of Candida (29% of cohort) and C. albicans (21% of cohort) in a subset of patients, although a smaller subject group had a similar reduction in Candida.

Although the authors found various correlations with intestinal inflammatory mediators, none of the participants had clinically evident gut inflammation. 

Ileal biopsies performed in a separate cohort of five patients showed clinically overt Crohn’s disease was associated with an expansion of IL-25/IL-17E-producing tuft cells and group 2 innate lymphoid cells, compared with levels before treatment with IL-17 inhibitors. Other research groups have shown microbial changes after biologic therapies, including a significant reduction in Escherichia coli after adalimumab, that appeared to make the microbiome more similar to the composition of healthy individuals.2

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In the current study, limitations stated by the authors include small cohort sizes, subject recruitment from different geographical areas, a phenotypically heterogenous population and different drugs used in the TNF inhibitor cohort. This type of study will need validation in larger prospective cohorts, the authors write. “Extending our results would also help us understand whether baseline gut microbiota can be used as predictors of biologic therapy response, as in the case of cancer immunotherapies.” 

“Although our study was correlative in nature, requiring validation and expansion, a better understanding of the biologic-associated gut microbial perturbations could potentially lead to precision medicine approaches in spondyloarthritis and psoriatic arthritis, as well as the ability to predict individuals who are at risk for adverse events,” says study author Julia Manasson, MD, Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine.

The study authors are working on further research to characterize gut microbial signatures of PsA in populations of genetically similar and identical individuals to control for confounding HLA. They are also exploring how microbial signatures in PsA can be altered with medium-chain fatty acid supplementation.

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Filed Under: Conditions, Research Reviews, Spondyloarthritis Tagged With: gut microbiota, Microbiome, PsA Resource Center, Psoriatic Arthritis, secukinumabIssue: February 2021

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