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Open research questions in Rheumatoid Arthritis Research and Therapies

638 gap statements mined from Rheumatoid Arthritis Research and Therapies papers in our 7.9M-paper local library, which holds 2,966 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • Current measures of inflammatory disease activity may not fully capture the mechanisms underlying chronic pain in RA. There is a need to investigate other factors such as central sensitization, which can contribute to chronic pain and other symptoms in RA. The relationship between central sensitization and psychosocial symptom burden in women with RA is not well understood.

    Beyond Pain Intensity: Central Sensitization and Psychosocial Symptom Burden in Women with Rheumatoid Arthritis · 2026 · DOI

  • The need to balance the benefits and risks of antirheumatic therapies on metabolic outcomes. The challenge of interpreting lipid changes observed during treatment due to the heterogeneous effects of antirheumatic therapies on lipid metabolism.

    Metabolic challenges in rheumatoid arthritis: a translational overview from pathogenesis to patient care · 2026 · DOI

  • The need to understand the interaction between chronic inflammation, antirheumatic therapies, and metabolic regulation. The lack of a comprehensive overview of the role of metabolic dysfunctions in RA. The need for a cardiometabolic monitoring algorithm to support daily patient care.

    Metabolic challenges in rheumatoid arthritis: a translational overview from pathogenesis to patient care · 2026 · DOI

  • The treatment of rheumatoid arthritis is complicated by the need to minimize the risk of hepatic injury in patients with primary biliary cholangitis. Methotrexate and leflunomide, commonly used conventional synthetic DMARDs in rheumatoid arthritis, are generally avoided or used with considerable caution in the setting of significant liver disease.

    Tocilizumab for active rheumatoid arthritis in a patient with concomitant primary biliary cholangitis: a case based review · 2026 · DOI

  • There is a lack of published evidence on the use of tocilizumab in patients with concomitant rheumatoid arthritis and primary biliary cholangitis. The evidence is restricted to isolated case reports, with no dedicated case series, cohort studies, comparative studies, or treatment registries.

    Tocilizumab for active rheumatoid arthritis in a patient with concomitant primary biliary cholangitis: a case based review · 2026 · DOI

  • The need for a reliable and safe method for synovial biopsy. The lack of standardization in synovial biopsy procedures. The importance of evaluating the diagnostic contribution of ultrasound-guided synovial biopsy.

    Safety, tissue adequacy, and diagnostic contribution of ultrasound-guided synovial biopsy: a retrospective multicenter observational study in a heterogeneous rheumatology cohort · 2026 · DOI

  • The gap in current research is the lack of consideration for smoking status and other factors in the analysis of cancer associations. There is a need for sensitivity analyses to improve the understanding of cancer risk in patients with immune-mediated inflammatory diseases.

    Interpreting the Early Cancer Peak in Immune-Mediated Inflammatory Diseases. Comment on Giordani et al. Cancer Association in Patients with Immune-Mediated Inflammatory Diseases: A Five-Year Nationwide Italian Cohort Study. Cancers 2026, 18, 1027 · 2026 · DOI

  • Predicting individual treatment response remains clinically challenging in RA patients. There is a need for a flexible and interpretable framework for predicting treatment outcomes. The current approaches to predicting treatment outcomes in RA have limitations, such as not being able to predict continuous disease activity scores.

    Predicting Disease Activity Score in Rheumatoid Arthritis Patients Treated with Biologic Disease-Modifying Antirheumatic Drugs Using Machine Learning Models · 2025 · DOI

  • The precise mechanisms of ITIH4 in RA remain unexplored. The role of ITIH4 in chemokine signaling in RA is not well understood. The potential receptors for ITIH4 in RA are not identified.

    ITIH4 in Rheumatoid Arthritis Pathogenesis: Network Pharmacology and Molecular Docking Analysis Identify CXCR4 as a Potential Receptor · 2024 · DOI

  • The optimal perioperative management of biologic disease-modifying antirheumatic drugs (bDMARDs) in inflammatory rheumatic disease (IRD) patients undergoing total joint arthroplasty (TJA) remains debated, with current guidelines based on low-to-moderate quality evidence.

    Perioperative management of biologic disease-modifying antirheumatic drugs in patients with inflammatory rheumatic diseases undergoing total joint arthroplasty: A nationwide population-based cohort study from Taiwan · 2026 · DOI

  • However, how macrophage plasticity and metabolic programming drive RA pathogenesis remains poorly understood.

    Defective macrophage plasticity exacerbates progression of inflammation in patients with rheumatoid arthritis · 2026 · DOI

  • Given the limited number of events and observational design, further large-scale studies with longer follow-up are warranted to confirm these findings.

    Real-world comparison of herpes zoster risk among five Janus kinase inhibitors in rheumatoid arthritis: The ANSWER cohort study · 2026 · DOI

  • Herpes zoster (HZ) is a common adverse event associated with Janus kinase inhibitors (JAKi); however, direct comparisons using real-world data are lacking, which we aimed to clarify.

    Real-world comparison of herpes zoster risk among five Janus kinase inhibitors in rheumatoid arthritis: The ANSWER cohort study · 2026 · DOI

  • Data on the concomitant use of Janus kinase inhibitors (JAKi) and tumor necrosis factor inhibitors (TNFi) are scarce.

    Combination therapy with JAK inhibitors and TNF inhibitors in severe refractory rheumatoid arthritis: A monocentric case series · 2026 · DOI

  • Diabetes Mellitus (DM) is a known risk factor for worse clinical outcomes among patient with Rheumatoid Arthritis (RA), yet the effect of glycemic control on RA treatment has not yet been investigated.

    The association between diabetes mellitus control and advanced anti-rheumatic treatment, among rheumatoid arthritis patients: A nation-wide based, retrospective, cohort study · 2026 · DOI

  • Yet, the association of SES with disease activity and SDFR on the long-term, within a contemporary, well-treated cohort and potential mechanisms underlying this association are not fully explored.

    Lower socioeconomic status is associated with a more severe course of rheumatoid arthritis: A 7-year follow-up study · 2026 · DOI

  • Caveolin‐1 (CAV‐1) is widely distributed in the membrane structures of immune cells and participates in the differentiation and homeostasis of CD4 + T cell subsets through signal transduction; however, its role in RA has not yet been investigated.

    Cyclodextrin Inhibits Caveolin‐1 to Regulate CD4 + T Cell Subset Differentiation and Ameliorate Rheumatoid Arthritis Progression · 2026 · DOI

  • B cells are key contributors to the immunopathogenesis of rheumatoid arthritis (RA), yet the expression profile of interleukin‐17 (IL‐17) receptors on human B cells remains incompletely defined.

    Expression Profile of the IL‐17 Receptor Family on Peripheral B Lymphocytes in Rheumatoid Arthritis · 2026 · DOI

  • Whether this delay impacts disease activity and radiographic progression over 1 year remains uncertain.

    One-month delay in MTX initiation on RA outcomes: 1-year ancillary analysis of the VACIMRA trial · 2026 · DOI

  • The underlying mechanisms remain unclear, with debate whether persistent symptoms reflect residual inflammation or non-inflammatory factors.

    Cytokine/chemokine profiles in rheumatoid arthritis patients who failed Boolean remission solely due to elevated patient global assessment · 2026 · DOI

  • Foot involvement is equally common and contributes significantly to disability, although it is often under-recognised in routine clinical practice.

    Rheumatoid arthritis beyond the textbook: Asymmetric hand deformities with rare bilateral hallux manifestations · 2026 · DOI

  • Sensitivity analyses excluding cancers detected within the first 12-24 months, restricting exposure to incident and well-defined autoimmune diseases, and accounting for healthcare utilization and smoking would help distinguish persistent disease-related risk from reverse causation and differential…

    Interpreting the Early Cancer Peak in Immune-Mediated Inflammatory Diseases. Comment on Giordani et al. Cancer Association in Patients with Immune-Mediated Inflammatory Diseases: A Five-Year Nationwide Italian Cohort Study. Cancers 2026, 18, 1027 · 2026 · DOI

  • Investigate the role of other macrophage subsets in RA pathogenesis, - Examine the effects of different therapeutic strategies on macrophage plasticity, - Study the relationship between macrophage metabolic programming and RA…

    Defective macrophage plasticity exacerbates progression of inflammation in patients with rheumatoid arthritis · 2026 · DOI

  • Further studies are needed to evaluate the long-term safety and efficacy of synovial biopsy, - Studies are needed to compare the diagnostic yield of synovial biopsy to other diagnostic modalities, - Research is needed to develop standardized protocols for synovial biopsy, - Studies are needed to evaluate the cost-effectiveness of synovial…

    Safety, tissue adequacy, and diagnostic contribution of ultrasound-guided synovial biopsy: a retrospective multicenter observational study in a heterogeneous rheumatology cohort · 2026 · DOI

  • Further studies are needed to investigate the mechanisms of central sensitization in rheumatoid arthritis, - Research should focus on developing more effective treatments for pain in rheumatoid arthritis, - Studies should explore the relationship between central sensitization and disease…

    Beyond Pain Intensity: Central Sensitization and Psychosocial Symptom Burden in Women with Rheumatoid Arthritis · 2026 · DOI

Most-cited papers in Rheumatoid Arthritis Research and Therapies

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Open questions raised by papers listed on this page include: (1) There is a need to investigate other factors such as central sensitization, which can contribute to chronic pain and other symptoms in RA (“Beyond Pain Intensity: Central Sensitization and Psychosocial Symptom Burden in…”, 2026); (2) The lack of a comprehensive overview of the role of metabolic dysfunctions in RA (“Metabolic challenges in rheumatoid arthritis: a translational overview from…”, 2026); (3) There is a lack of published evidence on the use of tocilizumab in patients with concomitant rheumatoid arthritis and primary biliary cholangitis (“Tocilizumab for active rheumatoid arthritis in a patient with concomitant…”, 2026); (4) The gap in current research is the lack of consideration for smoking status and other factors in the analysis of cancer associations (“Interpreting the Early Cancer Peak in Immune-Mediated Inflammatory Diseases.”, 2026); (5) How macrophage plasticity and metabolic programming drive RA pathogenesis remains poorly understood (“Defective macrophage plasticity exacerbates progression of inflammation in…”, 2026). 638 gap statements have been mined from Rheumatoid Arthritis Research and Therapies papers in our 7.9M-paper local library, which holds 2,966 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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