ReviewRheumatology (Oxford, England)2022
Mechanisms underlying DMARD inefficacy in difficult-to-treat rheumatoid arthritis: a narrative review with systematic literature search.
Review in Rheumatology (Oxford, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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.
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Who cites it
31 citing papers in PubMed.
- Bridging the gap: combining treat-to-target and difficult-to-treat strategies in the management of rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Geroscience insights into difficult-to-treat rheumatoid arthritis: the role of unhealthy aging, comorbidity, and therapeutic complexity.GeroScience · 2026Review
- Pathogenic Drivers of Difficult-to-Treat Rheumatoid Arthritis: Synovium and Beyond.International journal of molecular sciences · 2026Review
- Factors Associated with Difficult-to-Treat Rheumatoid Arthritis (D2T-RA): Real-World Evidence from a Single-Center Cross-Sectional Study.Journal of personalized medicine · 2026Article
- Frontiers in Rheumatoid Arthritis: Emerging Research and Unmet Needs in Pharmacologic Management.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Obinutuzumab as salvage anti-CD20 therapy in poly-refractory difficult-to-treat seropositive rheumatoid arthritis.Rheumatology advances in practice · 2026Article
- Mitochondrial Hub Genes in Rheumatoid Arthritis Identified by Machine Learning and Mendelian Randomization with Experimental Validation.Journal of inflammation research · 2026Article
- Biomarkers of treatment response in rheumatoid arthritis: from conventional markers to tissue immunophenotype.Frontiers in immunology · 2026Review
- Immunological heterogeneity in rheumatoid arthritis: challenges in early-stage stratification, non-response to targeted therapy, and the restoration of immune tolerance.Frontiers in immunology · 2026Review
- Failed resolution as a mechanistic basis of difficult-to-treat rheumatoid arthritis: stromal-myeloid crosstalk in the synovium and emerging resolution-restoring therapies.Frontiers in immunology · 2026Review
- Global Disease Control in Inflammatory Arthritis Patients with Fibromyalgia Multi-Failure to Biologic Drugs: Short-Term Impact of Target Therapies on Both Disease Courses.Journal of clinical medicine · 2025Article
- Article
- Efficacy and safety of abatacept in rheumatoid arthritis patients in Western region in Saudi Arabia: a multi-center study.BMC rheumatology · 2025Article
- Early-onset difficult-to-treat rheumatoid arthritis: proposal of data-driven predictors and temporal threshold.Arthritis research & therapy · 2025Observational
- Exploring difficult-to-manage axial spondyloarthritis: results from a Dutch clinical practice registry.Rheumatology (Oxford, England) · 2025Article
- Prevalence and characteristics of adults with difficult-to-treat rheumatoid arthritis in a large patient registry.Rheumatology (Oxford, England) · 2025Article
- Inflammatory and angiogenic serum profile of refractory rheumatoid arthritis.Scientific reports · 2025Article
- Obesity and fibromyalgia are associated with Difficult-to-Treat Rheumatoid Arthritis (D2T-RA) independent of age and gender.Arthritis research & therapy · 2025Article
- Difficult-to-treat rheumatoid arthritis: what have we learned and what do we still need to learn?Rheumatology (Oxford, England) · 2025Review
- Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Management of RA patients has significantly improved over the past decades. However, a substantial proportion of patients is difficult-to-treat (D2T), remaining symptomatic after failing biological and/or targeted synthetic DMARDs. Multiple factors can contribute to D2T RA, including treatment non-adherence, comorbidities and co-existing mimicking diseases (e.g. fibromyalgia). Additionally, currently available biological and/or targeted synthetic DMARDs may be truly ineffective ('true' refractory RA) and/or lead to unacceptable side effects. In this narrative review based on a systematic literature search, an overview of underlying (immune) mechanisms is presented. Potential scenarios are discussed including the influence of different levels of gene expression and clinical characteristics. Although the exact underlying mechanisms remain largely unknown, the heterogeneity between individual patients supports the assumption that D2T RA is a syndrome involving different pathogenic mechanisms.
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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.