Treatment response in rheumatoid arthritis is predicted by the microbiome: a large observational study in UK DMARD-naïve patients

Nathan P Danckert; Maxim B Freidin; Isabelle Granville Smith; Philippa M Wells; Maryam Kazemi Naeini; Alessia Visconti; Roger Compte; Alexander MacGregor; Frances M K Williams

doi:10.1093/rheumatology/keae045

Treatment response in rheumatoid arthritis is predicted by the microbiome: a large observational study in UK DMARD-naïve patients

Rheumatology (Oxford). 2024 Jan 30:keae045. doi: 10.1093/rheumatology/keae045. Online ahead of print.

Authors

Affiliations

¹ Department of Twin Research and Genetic Epidemiology, School of Life Course & Population Sciences, King's College London, London, UK.
² Department of Biology, School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK.
³ UK Dementia Research Institute, Imperial College London, London, UK.
⁴ Department of Brain Sciences, Imperial College London, London, UK.
⁵ Norwich Medical School, University of East Anglia, Norwich, UK.
⁶ Rheumatology Department, Norfolk and Norwich University Hospitals NHS Trust, Norwich, UK.
⁷ Guy's and St Thomas' NHS Trust, London, UK.

PMID: 38291926
DOI: 10.1093/rheumatology/keae045

Abstract

Objectives: Disease-modifying antirheumatic drugs (DMARDs) are first line treatment in rheumatoid arthritis (RA). Treatment response to DMARDs is patient-specific, dose efficacy is difficult to predict and long-term results variable. The gut microbiota are known to play a pivotal role in prodromal and early-disease RA, manifested by Prevotella spp. enrichment. The clinical response to therapy may be mediated by microbiota, and large-scale studies assessing the microbiome are few. This study assessed whether microbiome signals were associated with, and predictive of, patient response to DMARD-treatment. Accurate early identification of those who will respond poorly to DMARD therapy would allow selection of alternative treatment (e.g. biologic therapy), and potentially improve patient outcome.

Methods: A multicentre, longitudinal, observational study of stool- and saliva microbiome was performed in DMARD-naïve, newly diagnosed RA patients during introduction of DMARD treatment. Clinical data and samples were collected at baseline (n = 144) in DMARD-naïve patients and at six weeks (n = 117) and 12 weeks (n = 95) into DMARD-therapy. Samples collected (n = 365 stool, n = 365 saliva) underwent shotgun sequencing. Disease activity measures were collected at each timepoint and minimal clinically important improvement determined.

Results: In total, 26 stool microbes were found to decrease in those manifesting a minimal clinically important improvement. Prevotella spp. and Streptococcus spp. were the predominant taxa to decline following six weeks and 12 weeks of DMARDs, respectively. Furthermore, baseline microbiota of DMARD-naïve patients were indicative of future response.

Conclusion: DMARDs appear to restore a perturbed microbiome to a eubiotic state. Moreover, microbiome status can be used to predict likelihood of patient response to DMARD.

Keywords: Disease-modifying antirheumatic drugs; Gut microbiome; Minimal clinically important improvement; Rheumatoid arthritis; Shotgun metagenomic sequencing.