Spain: Gut microbiome can predict non-response to oral methotrexate (MTX) therapy in patients with new-onset rheumatoid arthritis (NORA), finds a recent study in the journal Arthritis & Rheumatology.
The findings support the value of the gut microbiome as a potential target in RA therapeutics and as a possible prognostic tool.
Oral methotrexate (MTX) remains the anchor drug for RA, still, up to 50% of patients do not achieve a clinically adequate outcome. Also, there is a lack of prognostic tools for treatment response before drug initiation. In the study, Carles Ubeda, CIBER en Epidemiología y Salud Pública, Madrid, Spain, and colleagues aimed to study whether inter‐individual differences in the human gut microbiome can aid in the prediction of MTX efficacy in new‐onset RA.
For the purpose, the researchers performed 16S rRNA gene and shotgun metagenomic sequencing on the baseline gut microbiomes of drug‐naïve, NORA patients (n=26). Results were validated in an additional independent cohort (n=21).
In order to gain insight into potential microbial mechanisms, ex vivo experiments plus metabolomics analysis evaluated the association between microbiome‐driven MTX depletion and clinical response.
Key findings of the study include:
The analysis revealed significant associations between the abundance of gut bacterial taxa and their genes with future clinical response, including orthologs related to purine and methotrexate metabolism.
Machine learning techniques were applied to the metagenomic data, resulting in a microbiome‐based model that predicts lack of response to MTX in an independent group of patients.
MTX levels remaining afterex vivo incubation with distal gut samples from pre‐treatment RA patients significantly correlated with the magnitude of future clinical response, suggesting a possible direct effect of the gut microbiome on MTX metabolism and treatment outcomes.
"Together, these results provide the first step towards predicting lack of response to oral MTX in NORA patients and support the value of the gut microbiome as a possible prognostic tool and as a potential target in RA therapeutics," concluded the authors.
The study titled, "The Pre‐treatment Gut Microbiome is Associated with Lack of Response to Methotrexate in New Onset Rheumatoid Arthritis," is published in the journal Arthritis & Rheumatology.
DOI: https://onlinelibrary.wiley.com/doi/abs/10.1002/art.41622