Could Microbiota Predict Response to Anti-TNF Agents in Spondyloarthritis?

While the pathophysiology of spondyloarthritis (SpA) remains largely unknown, the influence of microbiota is emerging as a direction of research. Overlap between SpA and inflammatory bowel disease is common, and the clinical remission of SpA is associated with normal digestive histology while persistent rheumatic symptoms are often associated with intestinal inflammation.

These phenomena led a team of French researchers to investigate whether there is a cross-influence between anti—tumor necrosis factor (anti-TNF) therapy and intestinal microbiota. In findings published this month in Scientific Reports, the investigators report that they have identified a taxonomic node in patients prior to anti-TNF therapy that can predict clinical response.

The researchers used stool samples to investigate the intestinal microbiota of 19 patients with SpA who had not previously had anti-TNF therapy both before and 3 months after they initiated treatment with an anti-TNF of the treating physicians’ choice.

The researchers then focused on 2 subgroups of patients: 5 who responded strongly to treatment and 8 who showed no response at 3 months, and found that a high proportion of microbiota of the Betaproteobacteria class and Burkholderiales order prior to anti-TNF treatment was associated with clinical response at 3 months after treatment, which suggests a potential biomarker for anti-TNF efficacy in patients with SpA.

Interestingly, no specific taxon of microbiota was observed to be consistently modified by anti-TNF agents, but patients who did not respond to treatment showed drastic differences before and after treatment in terms of composition of microbiota. Conversely, patients who responded strongly showed only a few mild differences in overall composition.

The researchers suggest that higher stability of microbiota composition is present in those who respond to anti-TNF therapy, and that such stability may be a good prognostic factor in itself. This hypothesis will require longitudinal long-term study in order to be confirmed, however.

“Overall diversity as well as presence or absence of specific taxa have been shown to be biomarkers of disease or response to treatment in other disorders,” write the authors, who point to evidence that patients with rheumatoid arthritis have altered gut and mouth microbiomes that are partially normalized after treatment with disease-modifying anti-rheumatic drugs. While the physiopathology of SpA may be different from that of other diseases, these results warrant further investigation, say the authors.

Reference

Bazin T, Hooks KB, Barnetche T, et al. Microbiota composition may predict anti-TNF alpha response in spondyloarthritis patients: an exploratory study. Sci Rep. 2018;85:446. PMID: 29615661.