ArticleAnnals of the rheumatic diseases2018
Methotrexate and BAFF interaction prevents immunization against TNF inhibitors.
Article in Annals of the rheumatic diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Risk factors for anti-drug antibody formation to infliximab: Secondary analyses of a randomised controlled trial.Journal of internal medicine · 2022Trial
- Methotrexate's effect on cells and adalimumab immunogenicity in axial spondyloarthritis: A mathematical study.PLoS computational biology · 2026Article
- Emerging mechanistic trends and clinical efficacy for methotrexate: Applications to inflammatory bowel disease.Pharmacological reviews · 2026Review
- Rapid on-off effects of methotrexate on lymphocytes may facilitate recovery of suppressed vaccine immunogenicity after its short-term methotrexate discontinuation in rheumatoid arthritis.Frontiers in immunology · 2026Article
- GRK2 dysfunction mediates acute kidney injury in murine administered methotrexate combined with omeprazole.Acta pharmacologica Sinica · 2026Article
- Assessing early therapeutic drug monitoring of adalimumab as a predictor of treatment efficacy and immunogenicity in rheumatic diseases: "early therapeutic drug monitoring of adalimumab".Clinical rheumatology · 2025Article
- Methotrexate - Safe Backbone for the Treatment of Rheumatoid Arthritis.Current rheumatology reviews · 2025Review
- Early monitoring of anti-infliximab antibodies by drug-tolerant assay predicts later immunogenicity and drug survival in rheumatic diseases.Rheumatology (Oxford, England) · 2025Observational
- Article
- Machine learning identifies a profile of inadequate responder to methotrexate in rheumatoid arthritis.Rheumatology (Oxford, England) · 2023Article
- Pharmacological strategies for mitigating anti-TNF biologic immunogenicity in rheumatoid arthritis patients.Current opinion in pharmacology · 2023Review
- Assessing Immunogenicity of Biologic Drugs in Inflammatory Joint Diseases: Progress Towards Personalized Medicine.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2022Review
- Withholding methotrexate after vaccination with ChAdOx1 nCov19 in patients with rheumatoid or psoriatic arthritis in India (MIVAC I and II): results of two, parallel, assessor-masked, randomised controlled trials.The Lancet. Rheumatology · 2022Article
- The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era.Rheumatology international · 2022Review
- Article
- Long-term exposure to monoclonal anti-TNF is associated with an increased risk of lymphoma in BAFF-transgenic mice.Clinical and experimental immunology · 2021Article
- BAFF predicts immunogenicity in older patients with rheumatoid arthritis treated with TNF inhibitors.Scientific reports · 2021Article
- Methotrexate reduces circulating Th17 cells and impairs plasmablast and memory B cell expansions following pneumococcal conjugate immunization in RA patients.Scientific reports · 2021Article
- Immunogenicity of biologic agents in rheumatology.Nature reviews. Rheumatology · 2021Review
- Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium.PLoS medicine · 2020Article
Corrections and comments
- Commented on by
- Erratum issuedCorrection:2021
Authors and funding
18 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTNF inhibitors (TNFi) can induce anti-drug antibodies (ADA) in patients with autoimmune diseases (AID) leading to clinical resistance. We explored a new way of using methotrexate (MTX) to decrease this risk of immunisation.
methodsWe treated BAFF transgenic (BAFFtg) mice, a model of AID in which immunisation against biologic drugs is high, with different TNFi. We investigated the effect of a single course of MTX during the first exposure to TNFi. Wild-type (WT) and BAFFtg mice were compared for B-Cell surface markers involved in MTX-related purinergic metabolism, adenosine production and regulatory B-cells (Bregs).We translated the study to macaques and patients with rheumatoid arthritis from the ABIRISK cohort to determine if there was an interaction between serum BAFF levels and MTX that prevented immuniation.
resultsIn BAFFtg but not in WT mice or macaques, a single course of MTX prevented immunisation against TNFi and maintained drug concentration for over 52 weeks. BAFFtg mice B-cells expressed more CD73 and CD39 compared to WT mice. MTX induced adenosine release from B cells and increased Bregs and precursors. Use of CD73 blocking antibodies reversed MTX-induced tolerance. In patients from the ABIRISK cohort treated with TNFi for chronic inflammatory diseases, high BAFF serum level correlated with absence of ADA to TNFi only in patients cotreated with MTX but not in patients on TNFi monotherapy.
conclusionMTX and BAFF interact in mice where CD73, adenosine and regulatory B cells were identified as key actors in this phenomenon. MTX and BAFF also interact in patients to prevent ADA formation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.