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

Objectives: Disease-modifying antirheumatic drugs (DMARDs) are a first-line treatment in rheumatoid arthritis (RA). Treatment response to DMARDs is patient-specific, dose efficacy is difficult to predict and long-term results are 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-naive, newly diagnosed RA patients during introduction of DMARD treatment. Clinical data and samples were collected at baseline (n = 144) in DMARD-naive 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-naive 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.