ReviewNature reviews. Rheumatology2021
Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis.
Review in Nature reviews. Rheumatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers, 3 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
164 citing papers in PubMed, 3 syntheses or guidelines pooled it, 286 citations in OpenAlex.
- Therapeutic approaches for difficult-to-treat rheumatoid arthritis: a systematic literature review of current evidence.RMD open · 2026Pooled it
- Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients.International journal of molecular sciences · 2022Pooled it
- EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis.Annals of the rheumatic diseases · 2022Guideline
- Deep molecular profiling of synovial biopsies in the STRAP trial identifies signatures predictive of treatment response to biologic therapies in rheumatoid arthritis.Nature communications · 2025Trial
- Low-dose IL-2 improved clinical symptoms by restoring reduced regulatory T cells in patients with refractory rheumatoid arthritis: A randomized controlled trial.Frontiers in immunology · 2022Trial
- Plant-Derived Heterocyclic Compounds: A Promising Review on Natural Remedies for Rheumatoid Arthritis Management and Their Mechanistic Insights in Inflammation and Joint Protection.Basic & clinical pharmacology & toxicology · 2026Review
- Rheumatoid arthritis: transarterial microembolization for refractory localized joint inflammation.Skeletal radiology · 2026Article
- Antagonism of P2X7 receptor function in synovial fibroblasts is a potential therapeutic manipulation in rheumatoid arthritis.Purinergic signalling · 2026Article
- Observational
- Difficult-to-treat, complex-to-manage, treatment-refractory spondyloarthritis: semantics or substance?Current opinion in rheumatology · 2026Review
- The value of arthroscopic synovectomy in the treatment of rheumatoid arthritis: A prospective cohort study.Clinical rheumatology · 2026Article
- Microfluidic-based biomimetic mitochondrial nanocomposite for targeted immunotherapy of rheumatoid arthritis via mitochondrial transplantation.Materials today. Bio · 2026Article
- A Vakognavine-Type Diterpenoid Alkaloid as FoxO1 Inhibitors against Rheumatoid Arthritis.Journal of the American Chemical Society · 2026Article
- The Role of Musculoskeletal Ultrasound in Psoriatic Arthritis: From Preclinical Detection to Treatment Monitoring.Current rheumatology reports · 2026Review
- Emerging trends in the management of difficult-to-treat rheumatoid arthritis: targeted treatments and non-pharmacological interventions.Rheumatology (Oxford, England) · 2026Review
- Bridging the gap: combining treat-to-target and difficult-to-treat strategies in the management of rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Stigmasterol ameliorates Freund's complete adjuvant-induced polyarthritis in rats.Inflammopharmacology · 2026Article
- Macrophage metabolic exhaustion and PANoptotic cell death drive chronic tissue inflammation in rheumatoid arthritis.Immunity · 2026Article
- Lipid droplet-induced T cell death sustains autoimmune tissue inflammation.Cell metabolism · 2026Article
- Nanoparticle Delivery Systems in Rheumatoid Arthritis: More Than Vehicles.Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Review
104 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite nearly three decades of advances in the management of rheumatoid arthritis (RA), a substantial minority of patients are exposed to multiple DMARDs without necessarily benefitting from them; a group of patients variously designated as having 'difficult to treat', 'treatment-resistant' or 'refractory' RA. This Review of refractory RA focuses on two types of patients: those for whom multiple targeted therapies lack efficacy and who have persistent inflammatory pathology, which we designate as persistent inflammatory refractory RA (PIRRA); and those with supposed refractory RA who have continued disease activity that is predominantly independent of objective evidence of inflammation, which we designate as non-inflammatory refractory RA (NIRRA). These two types of disease are not mutually exclusive, but identifying those individuals with predominant PIRRA or NIRRA is important, as it informs distinct treatment and management approaches. This Review outlines the clinical differences between PIRRA and NIRRA, the genetic and epigenetic mechanisms and immune pathways that might contribute to the immunopathogenesis of recalcitrant synovitis in PIRRA, and a possible basis for non-inflammatory symptomatology in NIRRA. Future approaches towards the definition of refractory RA and the application of single-cell and integrated omics technologies to the identification of refractory RA endotypes are also discussed.
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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.