Search Results (880)

Perioperative management of antirheumatic medications in adults with rheumatoid arthritis (RA) undergoing orthopedic surgery requires balancing postoperative infection and impaired wound healing against disease flare, pain, and delayed rehabilitation. This systematic review aimed to evaluate how perioperative continuation, withholding, interruption timing, restart timing, dose modification, or exposure to antirheumatic medications relates to postoperative outcomes in adults with RA undergoing arthroplasty and non-arthroplasty orthopedic procedures. PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched from database inception to 18 April 2026 for English-language full-text clinical studies. The primary outcomes were surgical site infection/periprosthetic joint infection, delayed wound healing, and postoperative RA flare. Secondary outcomes included reoperation, revision, readmission, mortality, venous thromboembolism, dislocation, and other procedure-specific complications. Original studies were classified as direct perioperative strategy evidence, medication-exposure evidence, or supportive clinical-context evidence. Forty-three original clinical studies were included, together with six non-original contextual sources. The evidence was predominantly observational, clinically heterogeneous, and of very low certainty. Methotrexate continuation was not associated with an evident increase in early postoperative complications, whereas direct evidence for other conventional synthetic agents was limited. Longer interruption of biologic or targeted synthetic therapy did not consistently reduce infection or wound-healing complications, while several studies associated treatment interruption with postoperative flare. Chronic baseline glucocorticoid exposure was associated with adverse outcomes but was clinically distinct from short-term perioperative administration; stress-dose supplementation was not directly evaluated. Medication decisions should therefore be individualized according to drug class, disease control, glucocorticoid burden, surgical procedure, and patient risk profile. Full article

Background: To compare retinal microvascular parameters assessed by optical coherence tomography angiography (OCTA) among patients with axial spondyloarthritis (axSpA) receiving different biologic and targeted synthetic therapies and to evaluate the association between smoking status and OCTA-derived retinal microvascular parameters. Methods: This cross-sectional study included 159 eyes of 82 patients with radiographic or non-radiographic axSpA receiving tumor necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i), or Janus kinase inhibitors (JAKi) for at least one year. At the time of examination, all patients had BASDAI scores below the established threshold for active disease (BASDAI < 4). Comprehensive ophthalmic evaluation and swept-source OCTA imaging were performed. Superficial capillary plexus vessel density and foveal avascular zone (FAZ) areas in both the superficial (SCP) and deep capillary plexus (DCP) were assessed. Statistical analyses were adjusted for age, sex, smoking status, history of uveitis, treatment duration, and ocular variables. Results: Significant differences were observed among treatment groups in the deep foveal avascular zone (DCP-FAZ) area (p = 0.0060). Post hoc analyses demonstrated larger DCP-FAZ values in patients receiving TNFi than in those receiving IL-17i (p = 0.0010), and larger values in the IL-17i group than in the JAKi group (p = 0.0151). No significant differences were observed in superficial FAZ area or superficial capillary plexus vessel density between treatment groups. Patients receiving JAKi were older and had a shorter treatment duration than those in the other groups. Smoking status was associated with a significantly smaller deep FAZ area (p = 0.0019), whereas no significant association was observed for superficial FAZ measurements. A weak positive correlation was found between intraocular pressure and deep FAZ area (r = 0.18, p = 0.0237), and treatment duration was weakly positively correlated with deep FAZ area (rho = 0.16, p = 0.0454). Conclusions: Retinal microvascular parameters differed among patients with axSpA receiving different classes of biologic and targeted synthetic therapies. Differences were observed primarily in the deep FAZ area, while smoking status was also associated with deep retinal microvascular parameters. Because of the cross-sectional design, these findings should be interpreted as associations rather than evidence of treatment effects. OCTA may provide a useful non-invasive method for assessing retinal microvascular characteristics in patients with axSpA. Further longitudinal studies are warranted to clarify the relationship between systemic therapies, smoking status, and retinal microvascular changes. Full article

While glucose-driven mitochondrial dysfunction has been proposed to promote vascular dysfunction responsible for saphenous vein graft failure (VGF) following bypass surgery, the impact of type 2 diabetes mellitus (T2DM) on mitochondrial function in human saphenous vein smooth muscle cells (HSVSMCs) responsible for maladaptive remodelling is unknown. Our aim was to identify signalling pathways that mediate any mitochondrial dysfunction in HSVSMCs in vitro and assess the impact of T2DM. HSVSMCs explanted from surplus HSV tissues from consenting T2DM and non-diabetic patients undergoing coronary artery bypass graft surgery were treated with known activators and inhibitors of the JAK/STAT and MAPK/ERK pathways. Following this, real-time oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) measures of mitochondrial function were then determined. Our findings revealed that both IL-6/sIL-6Rα trans-signalling complexes and platelet-derived growth factor-BB (PDGF-BB) significantly increased OCR in HSVSMCs from T2DM patients but not non-diabetic controls. Meanwhile, only PDGF-BB increased ECAR in HSVSMCs from T2DM patients but not in non-diabetic controls. The observed increases in OCR and ECAR were abolished by JAK1/2-selective inhibitor ruxolitinib. Furthermore, thrombin caused a significant increase in OCR, specifically in HSVSMCs from T2DM patients, and this effect was abolished by the MEK1/2-selective inhibitor trametinib. Both ruxolitinib and trametinib significantly reduced basal OCR and ECAR in HSVSMCs from both T2DM and non-diabetic patients. Together, these findings demonstrate a JAK/STAT- and MAPK/ERK-mediated regulation of mitochondrial function in HSVSMCs. As such, they represent potential targets for regulation of HSVSMC function that can be explored for drug development to limit saphenous VGF in T2DM. Full article

Objectives: Alopecia areata (AA) is a widespread autoimmune condition causing non-scarring hair loss, significantly affecting the quality of life. Despite its prevalence, data on diagnostic and treatment efficacy and the quality of patient care in Poland remain unstudied. The aim of this study was to assess the current clinical approaches to the diagnosis and management of alopecia areata by dermatologists in Poland and to highlight the challenges encountered by Polish patients. Methods: A cross-sectional study was conducted regarding dermatologists and AA patients in Poland. The data were gathered from distinct proprietary surveys: an original questionnaire for doctors, and DLQI, CDLQI, AAPPO, WPAI+CIQ:AS, and SF-36 questionnaires for patients. Results: The study included 100 dermatologists and 252 patients from Poland. The study revealed that the care provided to patients with alopecia areata is inadequate and lacks a comprehensive approach, despite the negative disease impact on patients’ quality of life. A number of physicians do not follow the diagnostic and treatment guidelines. Despite the registration of next-generation treatments like Janus kinase inhibitors, access to these medications remained limited until recently. Conclusions: Alopecia areata in Poland poses significant diagnostic, therapeutic, and psychosocial challenges. While clinical practice largely aligns with international recommendations, notable gaps remain in the use of validated severity tools, psychosocial assessment, and access to advanced therapies. The recent reimbursement of ritlecitinib represents a breakthrough, bringing Polish care in line with global standards. However, optimal management requires not only pharmacological advances but also interdisciplinary strategies integrating psychological support, patient advocacy, and public education to reduce stigma and improve overall quality of life for affected individuals. Full article

Acute liver failure (ALF) is a fulminant hepatic syndrome characterized by rapid hepatocellular destruction, severe impairment of liver function, and high mortality. Effective pharmacological interventions capable of limiting early hepatic injury remain lacking. Upadacitinib (UPA), a selective inhibitor for Janus kinase 1 (JAK1) with established anti-inflammatory activity, has not previously been investigated in experimental ALF. Consequently, the current study examined the hepatoprotective potential and underlying mechanisms of UPA in a lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALF murine model. Mice were pretreated with UPA (10 or 20 mg/kg) prior to LPS/D-GalN challenge. UPA significantly attenuated liver injury, as demonstrated by marked reductions in serum ALT, AST, ALP, and γ-GT levels, together with substantial improvement in hepatic histopathology, attenuation of necroinflammation, and reduction in neutrophil accumulation. UPA also restored hepatic redox balance through reduction in lipid peroxidation and nitrosative stress, alongside enhancement of antioxidant capacity. Mechanistically, UPA suppressed IFN-γ/JAK1/STAT1 signaling and downregulated NF-κB p65 and inducible nitric oxide synthase (iNOS) expression, with subsequent reduction in hepatic TNF-α production. In parallel, UPA inhibited MAPK pathway activation, including ERK1/2, JNK, and p38 signaling. Moreover, UPA attenuated hepatocellular apoptosis through suppression of active caspase-3 and Bax expression with restoration of Bcl-2 levels. The 20 mg/kg dose consistently produced greater biochemical, molecular, and histopathological protection than the lower dose. In conclusion, UPA confers significant protection against LPS/D-GalN-induced ALF through coordinated suppression of oxidative stress, inflammatory signaling, and apoptosis, primarily associated with inhibition of the IFN-γ/JAK1/STAT1 and TNF-α/NF-κB/MAPK pathways and modulation of the Bax/Bcl-2 ratio, underscoring its viability as a promising therapeutic candidate for ALF. Full article

Psoriasis is a chronic, autoimmune skin disease driven by persistent inflammation and immune dysfunction that severely impairs quality of life and is associated with serious comorbidities, including psoriatic arthritis, cardiovascular diseases (CVDs), and depression. Emerging epidemiological evidence suggests an association between psoriasis and an increased risk of certain malignancies, such as breast cancer (BC) and non-Hodgkin’s lymphoma (NHL), although the strength and consistency of these associations vary across study designs, and the underlying thrombo-inflammatory mechanisms remain incompletely understood. Several therapeutic approaches, including topical therapies, conventional systemic drugs (e.g., methotrexate and cyclosporine), and biological agents have been investigated for their potential associations with malignancy risk. However, the available evidence is heterogeneous and influenced by disease severity, treatment duration, cumulative exposure, and patient-related confounding factors. While some epidemiological studies have reported associations between conventional therapies and selected skin or hematological malignancies, combined or sequential treatment regimens further complicate the interpretation of treatment-related cancer risk. Similarly, Janus kinase (JAK) inhibitors have been associated with higher reported rates of lymphoma and non-melanoma skin cancer than tumor necrosis factor α inhibitors (TNFi-α) in some observational studies. Recent studies also highlight the clinical utility of inflammatory markers, specifically the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR) ratio, and systemic immune-inflammation index (SII), for monitoring systemic inflammation and treatment response, while certain therapies may additionally influence CVD risk. Despite these advances, substantial heterogeneity across observational studies, meta-analyses, and Mendelian randomization analyses preclude definitive conclusions regarding causality. Overall, this review synthesizes the current epidemiological and mechanistic evidence linking psoriasis, chronic inflammation, therapeutic interventions, cancer risk, and cardiovascular comorbidities, while highlighting the need for large prospective studies and standardized analytical approaches. Full article

Patients with inflammatory bowel disease (IBD) often require long-term immunosuppressive or advanced therapy, raising concerns about treatment-associated malignancy risk. This systematic review evaluated malignancy outcomes associated with biologic, advanced small-molecule, and thiopurine therapies in adults with IBD. PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception through June 2025, with supplementary screening of Google Scholar and reference lists. Eligible primary studies included randomized controlled trials and prospective or retrospective cohort studies evaluating malignancy outcomes. Thiopurines were included because they remain clinically important comparators and are central to combination-therapy risk. The Newcastle–Ottawa Scale and the Cochrane risk-of-bias tool were used for observational studies and randomized trials, respectively. Because of substantial clinical and methodological heterogeneity, we did not perform a de novo meta-analysis; pooled estimates from previously published meta-analyses are reported only as contextual evidence. Twenty-eight studies met the inclusion criteria. Thiopurines showed the most consistent malignancy associations, including lymphoma, non-melanoma skin cancer (NMSC), acute myeloid leukemia/myelodysplastic syndrome, and urinary tract cancer. Anti-tumor necrosis factor (anti-TNF) monotherapy was not associated with a clear increase in overall cancer incidence, although a modest lymphoma signal was reported in some datasets. Combination anti-TNF plus thiopurine therapy showed the strongest lymphoma signal. Current evidence has not demonstrated an increased malignancy risk with vedolizumab or ustekinumab, including in available cohorts of patients with prior malignancy; however, confidence is limited by observational designs, small event numbers, heterogeneous cancer histories, and limited follow-up. IBD-specific data for Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators remain comparatively immature, and long-term surveillance is required. Overall, treatment decisions should integrate absolute baseline risk, age, smoking, prior malignancy, prior NMSC, Epstein–Barr virus-related risk, disease-related cancer risk, and cumulative immunosuppressive exposure. Full article

Glioblastoma (GBM), classified as grade 4 of high-grade glioma (HGG) under the 2021 World Health Organization (WHO) Classification of Central Nervous System Tumors (WHO CNS-2021), is the most aggressive primary brain tumor in adults. However, with maximal surgical resection, concurrent radiotherapy, and temozolomide (TMZ) chemotherapy, a median patient survival is still between 14 and 16 months. The persistent failure of current treatments is not only traceable to the molecular complexity of tumor cells but is fundamentally shaped by the tumor microenvironment (TME), in which non-neoplastic cells collectively constitute up to half of the total tumor mass. Reactive astrocytes, microglia, tumor-associated macrophages (TAMs), and oligodendrocyte precursor cells (OPCs) are no longer regarded as passive bystanders but as active architects of tumor progression, immune evasion, and therapy resistance. In this comprehensive review, we systematically describe the molecular mechanisms of glial–tumor crosstalk across all three major glial cells. Reactive astrocytes sustain tumor invasion and chemoresistance through connexin-43 gap junctions, bidirectional IL-6/JAK-STAT3 paracrine signaling, and extracellular vesicle-mediated oncogenic reprogramming. Microglia and TAMs undergo profound transcriptional reprogramming via PI3K/Akt/mTOR and CSF-1R signaling, adopting immunosuppressive states that exclude cytotoxic T cells, maintain glioma stem cell (GSC) niches, and drive angiogenesis. OPCs are now underexplored, accumulate at the tumor border, and cooperate with macrophages via Notch and Wnt/β-catenin pathways to establish a therapy-resistant GSC niche at the precise site of post-surgical recurrence. We further address glial–glial interactions as an independent regulatory layer and integrate recent spatial transcriptomic (ST) results revealing a structured, multi-glial niche that governs drug penetration. Finally, we critically evaluate emerging therapeutic strategies targeting these glial–tumor interfaces, including CSF-1R inhibitors, STAT3 modulators, CD47/SIRPα blockades, and engineered extracellular vesicle-based delivery systems. Understanding and targeting the glial ecosystem is an inseparable new field to explore. Full article

Vitiligo is a chronic autoimmune disease characterized by the loss of melanocytes, resulting in the appearance of depigmented patches on the skin. The aim of the present review is to discuss current therapeutic methods and to outline promising directions for the treatment of this dermatosis. The review describes pathogenetic mechanisms, including the role of oxidative stress, immune dysregulation, and the JAK/STAT pathways, which constitute the foundation of contemporary therapeutic interventions. The efficacy and safety of topical treatments (corticosteroids, calcineurin inhibitors, JAK inhibitors), phototherapy (NB-UVB, PUVA, excimer laser), combination therapies, and surgical methods such as cellular and tissue grafts are discussed. Data indicate that the combination of phototherapy with topical agents enhances repigmentation efficacy, and JAK inhibitors represent promising drugs in targeted therapy. Particular value is attributed to preparations modulating the immune response and to melanocyte transplantation techniques, which emerge as highly effective and forward-looking treatment options for vitiligo. Nevertheless, effective management of vitiligo requires a multidirectional approach combining pharmacological, immunomodulatory, and regenerative interventions. Full article

Background: Janus kinase inhibitors (JAK inhibitors) have expanded therapeutic options for rheumatoid arthritis (RA), although factors associated with treatment response in routine clinical practice remain incompletely defined. Objectives: This study aimed to evaluate clinical, treatment-related and pharmacogenetic factors associated with response to different JAK inhibitors in patients with RA. Methods: An ambispective observational real-world cohort study was conducted in patients with RA treated with tofacitinib, baricitinib, filgotinib, or upadacitinib. Disease activity was assessed at 3 and 6 months using the Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP). Clinical response was evaluated according to European Alliance of Associations for Rheumatology (EULAR) response criteria, low disease activity (LDA), and remission thresholds. Clinical, laboratory, and treatment-related variables were collected, and selected single-nucleotide polymorphisms (SNPs) in JAK1, JAK2, and JAK3 genes were genotyped. Bivariate and multivariable analyses were performed to identify variables associated with treatment outcomes. Results: Lower baseline inflammatory burden and lower disease activity were consistently associated with higher probabilities of EULAR response, LDA, and remission across JAK inhibitors. Treatment-related factors were also associated with improved outcomes. Pharmacogenetic associations were heterogeneous and drug-specific, with the most recurrent exploratory signals involving JAK2 variants. However, these genetic findings showed variability across outcomes and time points. Conclusions: In this real-world RA cohort, clinical and treatment-related factors were the most consistent variables associated with response to JAK inhibitors. Pharmacogenetic variation within the JAK pathway, particularly involving JAK2, may contribute to drug-specific variability in response, but these findings should be considered exploratory because of the limited sample size, multiple comparisons, and sparse genotype subgroups. Larger independent studies are required before JAK genotyping can be incorporated into individualized treatment strategies. Full article

Heart failure with preserved ejection fraction (HFpEF) is an increasingly common form of heart failure (HF) that is best understood as a systemic, multiorgan syndrome rather than a disease of left-ventricular filling alone. This review has three specific aims: first, to synthesize genetic and molecular pathways that are most relevant to non-ischemic HFpEF; second, to distinguish HFpEF-enriched mechanisms from evidence extrapolated from ischemic cardiomyopathy or HFrEF; and third, to consider translational implications for populations with high consanguinity, including the Kingdom of Saudi Arabia. The available evidence indicates that chronic inflammatory signaling involving CCL2, CCL5, TLR3, PTGS2/COX-2, IL-6/JAK/STAT3, NF-kB, and NLRP3 acts upstream of endothelial dysfunction, nitric-oxide/cGMP/PKG impairment, mitochondrial reactive oxygen species generation, and fibroblast activation. Extracellular-matrix regulators including ASPN, COL1A1, and MMP2 then amplify collagen deposition and myocardial stiffness, whereas mitochondrial genes and proteins such as ATP5C1 contribute to impaired oxidative phosphorylation, reduced ATP reserve, defective fatty-acid oxidation, and blunted mitophagy. Protein-quality-control pathways involving HSP90AA1, CCT2/CCT5, PSMA3, and stress-responsive STAT3 further link metabolic stress to proteotoxic injury. Epigenetic mechanisms, including DNA methylation and microRNAs such as miR-155, miR-1297, and miR-4649-3p, add a regulatory layer that may improve risk stratification but remains insufficiently validated for routine clinical use. In high-consanguinity settings, recessive cardiomyopathy variants can cluster in families and contribute to earlier NIHF presentations; however, population-level HFpEF-specific variant frequencies remain limited, and findings from HFrEF or dilated cardiomyopathy should be interpreted as candidate pathway evidence rather than definitive HFpEF markers. Translationally, SGLT2 inhibitors, mineralocorticoid-receptor antagonism, biomarker panels, and structured genetic evaluation provide the most clinically actionable bridge from molecular mechanisms to precision HFpEF care. Full article

Hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality worldwide, is driven by complex interactions between genetic mutations and reversible epigenetic alterations. Among these, aberrant DNA methylation, histone modifications, and dysregulated noncoding RNAs (ncRNAs) play central roles in hepatocarcinogenesis, tumor progression, and therapy resistance. Epigenetic changes not only regulate key oncogenic pathways, including JAK/STAT and RAS, but also contribute to tumor immune evasion and heterogeneity. Unlike genetic mutations, epigenetic alterations are reversible, offering unique opportunities for therapeutic targeting. This review highlights recent advances in understanding the epigenetic landscape of HCC, identifies promising biomarkers for early detection and prognosis, and evaluates emerging epigenetic therapies (including DNMT, HDAC, and BET inhibitors as well as ncRNA-based strategies). Although these therapies have shown tumor-suppressive or treatment-sensitizing effects in preclinical models, their clinical translation remains limited by modest efficacy, small early-phase trials, treatment-related adverse events, and insufficient biomarker-guided patient selection. These insights may support more precise diagnostic and therapeutic strategies for HCC. Full article

Signal transducer and activator of transcription 3 (STAT3) drives multiple hallmarks of tumorigenesis, making it a validated therapeutic target for diverse cancers. The 1,4-naphthoquinones, such as plumbagin (PL), exhibit anticancer activity via inhibiting STAT3 phosphorylation and dimerization, but their severe cytotoxicity precludes clinical translation. Here, we screened 23 PL derivatives for STAT3 inhibitory activity and normal cell cytotoxicity, identifying III-1a as the optimal candidate with superior STAT3 inhibition and reduced toxicity compared to PL. Molecular docking and cellular thermal shift assay (CTESA) revealed that III-1a binds to the L244 residue within the coiled-coil domain (CCD) of STAT3. In vitro, III-1a dose-dependently suppressed JAK/STAT3 signaling in oral squamous cell carcinoma (OSCC), particularly STAT3 Ser727 phosphorylation. It inhibited STAT3-mediated epithelial—mesenchymal transition (EMT) and induced ferroptosis, thereby attenuating OSCC proliferation, invasion and migration. STAT3 knockdown abrogated its anti-tumor effects, and in vivo studies further confirmed its efficacy against OSCC growth. Collectively, this study identifies a novel PL-derived STAT3 inhibitor targeting STAT3 CCD to regulate EMT and ferroptosis, providing a promising therapeutic candidate for OSCC. Full article

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by substantial clinical and immunological heterogeneity. Once considered primarily a disorder of epidermal barrier dysfunction, AD is now recognized as a complex systemic inflammatory condition involving dysregulated immune responses, epithelial-derived signaling, neuroimmune interactions, and diverse molecular endotypes. Advances in molecular immunology have substantially improved understanding of the cytokine networks underlying disease pathogenesis and have accelerated the transition toward precision medicine approaches in AD. This narrative review summarizes current evidence regarding the immunopathogenesis of AD, focusing on the interplay between classical and emerging cytokine pathways, biomarker development, and recent therapeutic innovations. While interleukin (IL)-4 and IL-13 remain central drivers of type 2 inflammation and barrier impairment, additional mediators including IL-31, IL-33, IL-22, thymic stromal lymphopoietin (TSLP), and OX40/OX40L signaling, and the emerging Th9/IL-9 axis contribute to chronic inflammation, neuroimmune activation, epidermal remodeling, pruritus, and disease heterogeneity. Comparative evaluation of these pathways supports the identification of distinct immunological endotypes relevant to disease stratification and targeted therapy. The review further discusses current and emerging biomarkers associated with disease severity, therapeutic responsiveness, and inflammatory profiling, including cytokine signatures, serum biomarkers, and transcriptomic approaches. Recent advances in biologic therapies, Janus kinase (JAK) inhibitors, and novel cytokine-targeted interventions are discussed within the context of a precision medicine framework integrating immunological profiling, molecular endotyping, and mechanism-based therapeutic innovation. Continued advances in biomarker discovery, multi-omics technologies, and predictive therapeutic algorithms are expected to further refine disease stratification and support increasingly individualized management strategies for patients with AD. Full article

The introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) has significantly enhanced the prognosis for patients with rheumatoid arthritis (RA). Nevertheless, improving quality of life remains a major clinical challenge requiring the implementation of multidirectional therapeutic measures. Pain reduction plays a particularly important role in this context, representing one of the primary treatment goals for many patients. Scientific evidence indicates that effective pain management is a crucial predictive factor for the improvement of mental and physical health in patients with RA. The aim of this literature review was to summarise the mechanisms of action of Janus kinase inhibitors (JAKi), with particular emphasis on their modulation of pain generation and transmission. Furthermore, the study aimed to compare the results of clinical studies and assess the actual effectiveness of these drugs in reducing pain in clinical practice. JAKi exhibit peripheral analgesic effects by directly reducing the production of pro-nociceptive cytokines and modulating macrophage polarisation. Moreover, they influence central pain processing mechanisms by modulating the IL-6/JAK/STAT3 pathway and by reducing microglial and astrocyte proliferation in the dorsal horn of the spinal cord. The results of randomised clinical trials confirm that JAKi provide rapid, clinically significant pain reduction. Some studies also point to the persistence of this effect over a longer period, and to their greater efficacy compared with conventional disease-modifying antirheumatic drugs (cDMARDs) and bDMARDs. The efficacy of this group of drugs has also been noted in patients with an inadequate response to prior therapy with biological drugs. A key focus of future research remains determining the optimal timing for introducing JAKi in the treatment of RA and identifying predictive factors to enable the selection of patients most likely to benefit from this class of drugs. Full article