AB0469 PROTON PUMP INHIBITORS MAY IMPAIR RESPONSE TO TNF-INHIBITORS IN SPONDYLOARTHRITIS PATIENTS
Authors: M. Masson, M. Kostine, T. Barnetche, A. Saraux, A. Ruyssen-Witrand, T. Thomas, D. Wendling, M. E. Truchetet, C. Richez, T. Schaeverbeke
Journal: Annals of the Rheumatic Diseases (2021)

Background: Considering the potential role of the gut microbiota in the pathophysiology of spondyloarthritis (SpA) as in the therapeutic response to biologics (1), we evaluated the hypothesis that co-medications known to interfere with the gut microbiota could impair the therapeutic response to TNF-inhibitors (TNF-i) in SpA patients. This was first suggested by the results of a retrospective cohort showing that a co-medication with proton pump inhibitors (PPIs), non-steroidal anti-inflammatory drugs (NSAIDs) or antibiotics was significantly associated with a decreased chance to respond to a first TNF-I, independently of each other (2). Objectives: To validate in a replication cohort the potential negative association between therapeutic response to TNF-i and co-medication with commonly used drugs. Methods: Demographic information and disease characteristics were retrospectively collected. Patients were classified as responder (R) or non-responder (NR) according to the BASDAI (&lt; 40/100) value at month 6 or to the clinician judgment (when BASDAI was not available). We collected all drugs known to interfere with the gut microbiota that were administered 1 month before and during the first 3 months of the TNF-i treatment. We only considered drugs given to more than 5% of patients. Univariate and multivariate analyses were performed to evaluate the relationship between co-medications, predictors of response known from literature and TNF-i response. All analyses were computed on STATA 13.1 with a statistically significant threshold of 0.05. Results: We included from 4 different centres 185 patients having axial SpA with radiographic or magnetic sacroiliitis in 75% and 73% of cases, respectively. One third of them had peripheral involvement. 73% were B27 positive. TNF-i administrated were infliximab (8%), etanercept (22%), adalimumab (44%) golimumab (19%), certolizumab (7%). 127 patients (69%) were considered as R. 59.4% of patients who received NSAIDs were R, compared to 81% not treated with NSAIDs (p&lt; 0.0001). 43,3% of patients receiving PPIs were R compared to 83% of patients PPI free (p&lt; 0.0001). Differences were not significant for antibiotics, methotrexate (MTX), psychotic drugs and corticosteroids. Considering known predictors of response, a magnetic sacroiliitis and the age at TNF-i initiation were significantly associated with a higher proportion of R patients (p=0.048 and 0.018 respectively). In multivariate analysis, PPIs intake remained associated with a poorer response to a first TNF-i (p&lt;0.001), even though 88% of patients exposed to PPIs received also NSAIDs. Univariate analysis Multivariate analysis Odd Ratio (95% Confidence Interval) Gender 1.43 (0.76; 2.72) Disease duration 1.02 (0.99; 1.06) Age at TNF-I initiation 0.97 (0.95; 0.995) 0.97 (0.94; 0.999) Magnetic sacroiliitis 0.46 (0.21; 0.99) 0.63 (0.26; 1.52) Baseline BASDAI 1.02 (0.99;1.04) Baseline CRP 0.99 (0.98; 1.02) Positive B27 0.81 (0.4;1.68) Peripheral involvement 0.79 (0.4; 1.56) NSAIDs 2.91 (1.47; 5.77) 1.08 (0.41; 2.79) PPIs 6.4 (3.25; 12.7) 6.9 (2.8;17) Antibiotics 1.87 (0.84; 4.16) Psychotics 1.94 (0.75; 4.97) Corticosteroids 1.11 (0.39; 3.11) Methotrexate 2.29 (0.97; 5.38) Conclusion: Co-medication with PPIs was considered as an independent factor associated with TNF-i failure. The hypothesis that this effect is due to their interference with the gut microbiota is only speculative but, regardless of the reason for this interaction, clinicians should be aware of the potential negative effect on TNF-i response. References: [1]Bazin, T., Hooks, K.B., Barnetche, T. et al. Microbiota Composition May Predict Anti-Tnf Alpha Response in Spondyloarthritis Patients: an Exploratory Study. Sci Rep 8, 5446 (2018). https://doi.org/10.1038/s41598-018-23571-4 [2]Masson M, Kostine M, Barnetche T, Truchetet ME, Richez C, Schaeverbeke T. Ab0661 Co-Medications May Alter the Response to Tnf-Inhibitors in Spondyloarthritis Patients: A Pharmacomicrobiomic Effect? Annals of the Rheumatic Diseases. 1 juin 2020;79(Suppl 1):1625–6. Disclosure of Interests: None declared.