JAK Inhibitors Research Articles

Treatment of an Indolent T-Cell Lymphoma of the Gastrointestinal Tract Harboring STAT3::JAK2 With Jakafi (Ruxolitinib) With Significant Clinical Improvements.

Indolent T-cell lymphoma of the gastrointestinal tract (ITCL-GI) is a rare primary T-cell lymphoma from the gastrointestinal (GI) tract, there has been no documented successful treatment at the present time. A CD4(+)/CD8(-) ITCL-GI with STAT3::JAK2 fusion was treated with Jakafi (Ruxolitinib), which resulted in significant clinical improvements. Next generation sequencing is highly recommended for any new diagnosis of CD4(+)/CD8(-) ITCL-GI in order to detect if STAT3::JAK2 can be found in order to treat the patient with JAK2 inhibitor such as Jakafi (Ruxolitinib). The authors have confirmed clinical trial registration is not needed for this submission.

Efficacy and Safety of JAK Inhibitors in the Management of Vitiligo: A Systematic Review and Meta-analysis.

Vitiligo, a chronic skin disease affecting 1-2% of the global population, is associated with significant impairment in quality of life. Current pharmacological treatment options have limited efficacy and considerable side effects. Recent studies have shown promising results when using Janus kinase inhibitors (JAKis). Despite these favourable findings, there remains a critical need for comprehensive data on the efficacy and safety of JAKi in the treatment of vitiligo. Three databases were searched for studies on patients with vitiligo treated with oral or topical JAKi, with or without conventional therapy. Placebo or vehicle cream were comparators in randomised controlled trials (RCTs). Outcomes included a 75% improvement in Facial-Vitiligo Area Scoring Index (F-VASI), mean Vitiligo Area Scoring Index (VASI) improvement, repigmentation percentage and adverse events. We performed three analyses: one using RCT data, one from case reports and a novel cohort of JAKi-treated patients from case reports. The protocol is registered with PROSPERO (CRD42023445503). Among the 35 articles identified, 19 were included in the statistical analyses. A meta-analysis of three randomised controlled trials (RCTs) on topical Janus kinase inhibitors (JAKis) suggested that patients treated with JAKi were more likely to achieve Facial Vitiligo Area Scoring Index 75 (F-VASI75) than those using vehicle cream (risk ratio (RR) 3.47, 95% confidence interval (CI) 0.98-12.22), with no significant difference in adverse events between groups (RR 1.27; 95% CI 0.88-1.82). A meta-analysis of four single-arm trials showed a 43.8% mean Vitiligo Area Scoring Index (VASI) improvement (95% CI 0.71-0.93). A cohort (n = 28) from case reports and series revealed significant repigmentation increases of 48.7% and 63.7% (p = 0.0018; p < 0.001) in patients treated with JAKi alone or with narrowband ultraviolet B (UVB). However, data were insufficient to determine if combination treatments were superior to JAKi alone. Our systematic review evaluated the efficacy and safety of JAKi for vitiligo using data from RCTs, single-arm trials and case reports. While topical ruxolitinib showed promising but non-significant results in RCTs, single-arm trials and case studies highlighted significant repigmentation, particularly with oral JAKis combined with other therapies. Oral JAKis showed effectiveness but require caution due to potential adverse effects such as immune suppression and cardiovascular risks. Furthermore, it is important to acknowledge that a considerable proportion of patients do not respond to these therapies. Additional RCTs are needed to address long-term safety, optimise application strategies and establish standardised endpoints for combination therapies.

Advances in Axial Spondyloarthritis Treatment: The Role of Janus Kinase Inhibitors

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease affecting the spine, peripheral joints and entheses, driven by dysregulated immune cell pathways, particularly the Janus kinase-signal transducer and activator of transcription (JAK‑STAT) pathway. While non‑steroidal anti‑inflammatory drugs and biologic disease-modifying anti-rheumatic drugs (DMARDs) (e.g., tumour necrosis factor inhibitors [TNFi] and interleukin inhibitors [IL‑17i]) are standard treatments. However, many patients show inadequate responses, necessitating alternative therapies. JAK inhibitors (JAKi), including tofacitinib, upadacitinib and filgotinib, offer targeted benefits by blocking the JAK‑STAT pathway to reduce pro-inflammatory cytokine transcription. Clinical trials have demonstrated that tofacitinib significantly improves ankylosing spondylitis outcomes, achieving superior Assessment of Spondyloarthritis International Society 20 and 40 (ASAS20 and ASAS40) responses compared to placebo. Upadacitinib has consistently shown efficacy across both radiographic and non‑radiographic axSpA in the SELECT‑AXIS trials, while the phase II TORTUGA trial reported that filgotinib significantly reduced disease activity, with greater improvements in ASDAS and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores compared to placebo. Mild side effects, such as nasopharyngitis and increased creatine phosphokinase levels, have been observed without conclusive links to severe adverse events like malignancies or cardiovascular complications. Thorough screening for tuberculosis and viral hepatitis is essential before initiating JAKi therapy. Moreover, for patients with comorbid inflammatory bowel disease, where TNFi may be unsuitable, tofacitinib provides an effective alternative. Its oral formulation enhances patient compliance and, combined with favourable cost‑effectiveness data, positions JAKi as attractive alternatives to conventional biologic therapies. Current evidence suggests that JAKi are a promising option for axSpA patients unresponsive to conventional or biologic DMARDs. However, long-term studies are needed to compare their efficacy and safety with TNFi and IL-17i.

Granuloma annulare: modern concepts of pathogenesis and pathogenetically based therapy (literature review)

Granuloma annulare is a chronic, benign, non-infectious skin disorder that causes ring-shaped papules, most commonly on the hands and feet. The condition is considered rare, according to some data, it affects less than 0.04% of the population. However, in recent years there has been an increase in the incidence of dermatosis, which is associated with the high prevalence of infectious diseases, including infections caused by the SARS-CoV-2 coronavirus. The pathogenesis of granuloma annulare has not been fully deciphered; nevertheless, comparative analysis of a wide range of biomarkers in biopsies of affected skin has shown differences in the expression of genes involved in regulation of innate immunity, Th1 and Th2 lymphocytes, and Janus kinases. Associations of granuloma annulare with endocrine, immune, and autoimmune diseases, malignant neoplasms, as well as the triggering role of infections and vaccinations, are subjects of discussion, despite advances in understanding the molecular mechanisms of disease development. The treatment of granuloma annulare presents quite complex challenge. Topical corticosteroids can be effective in localized forms of the disease. Calcineurin inhibitors can be used in combination with them. For disseminated forms of the dermatosis, narrowband medium wave ultraviolet therapy at 311 nm, PUVA, and 308 nm excimer ultraviolet light therapy are prescribed. There are descriptions of the effectiveness of antibacterial drugs. Currently, TNF-α inhibitors, JAK inhibitors and IL-23 inhibitors are proposed as targeted therapy for granuloma annulare. The basis for this recommendation is the latest information about the pathogenesis of granuloma annulare. The presented literature review systematizes modern concepts of molecular and cellular mechanisms of granuloma annulare development, infectious and non-infectious triggers of inflammation, the role of endocrine, immune and oncological pathology as predisposing factors. Significant importance is given to the analysis of treatment methods of the disease.

Ritlecitinib in Clinical Practice: A Real-World Study of Efficacy, Safety, and Prior JAK Inhibitor Impact in Alopecia Areata.

Ritlecitinib at 50 mg QD showed promising efficacy and acceptable safety in Chinese patients with moderate-to-severe AA, regardless of previous JAKi therapy.

Paradoxical Activation of Entheseal Myeloid Cells by JAK1 and TYK2 Inhibitors via IL10 Antagonism.

JAK inhibition (JAKi) is effective in seronegative spondyloarthropathy (SpA) spectrum disorders, but TYK2 inhibition failed in SpA spectrum ulcerative colitis, and tofacitinib showed minimal benefit in Crohn's Disease, which highlights the complex role for JAK-STAT signaling in different inflammatory processes. In this study, we investigated whether JAKi might paradoxically activate entheseal innate immunity and aimed to identify the key regulatory cytokines involved in this process. Spinal entheseal tissue was activated with TLR agonists, including TLR4 and IL-1 family proteins and entheseal T cell were activated with anti-CD3/anti-CD28 plus IL-23/IL-1β. JAKi via upadacitinib (JAK1/JAK2), deucravacitinib (TYK2) and ritlecitinib (JAK3) inhibition was evaluated using multiplex cytokine assays, intracellular flow and bulk RNAseq and cytokine blocking or stimulation. Following IFNγ stimulation, JAK1 inhibition blocked STAT1 phosphorylation in entheseal cells and strongly blocked activated entheseal T cell TNFα, IL-17A and IL-17F production. The opposite effect was evident in entheseal myeloid cell with exaggerated TLR4 and other adjuvant-mediated cytokine production including IL-23 (~10-fold increase; p < 0.001) or TNFα (~10-fold increase; p < 0.0001). This myeloid effect was induced by upadacitinib and deucravacitinib, but not ritlecitinib, suggesting IL-10R JAK1/TYK2 signaling. Bulk RNAseq showed multifaceted impact of JAKi on myeloid activation with strong M1 type monocyte polarisation under TLR4 stimulation and JAK1 inhibition confirmed by flow cytometry. Direct IL-10 inhibition recapitulated inflammatory cytokine elevations and IL-10R agonist largely, but not completely, rescued this phenotype. These findings help explain the emergent efficacy of TYK2 blockade in SpA spectrum related arthritis that is not IL-10 dependent but indicates why such strategies may not be a panacea for SpA spectrum disorder related intestinal inflammation.

Inflammatory Bowel Diseases (*DIIS) Therapies Biologics For The Management Of Crohn’s Disease And *Ulcerative Colitis

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic diseases of the gastrointestinal tract characterized by recurrent inflammation, significant functional impact and impaired quality of life. The treatment of these diseases has undergone important advances in recent decades, especially with the introduction of biological therapies. This study aimed to carry out a systematic review of the literature on the efficacy and safety of biological therapies in the management of CD and CRU. The search was carried out in the PubMed, SciELO, LILACS, Embase and Web of Science databases, resulting in the inclusion of 37 studies published between 2013 and 2024. The results showed that anti-TNF agents (infliximab, adalimumab, among others) are the most widely used and widely studied, with consolidated efficacy in inducing and maintaining remission. However, therapeutic failures associated with immunogenicity are common. Vedolizumab and ustekinumab have emerged as effective options with a favorable safety profile. JAK inhibitors, such as tofacitinib, have shown good results in CR, although they require greater vigilance due to potential adverse effects. The discussion highlighted the importance of a personalized approach, guided by treat-to-target strategies and the use of biomarkers. It is concluded that biological therapies have revolutionized the treatment of IBD, but the appropriate choice requires careful clinical evaluation, continuous monitoring and equitable access to technologies. Keywords : Crohn’s disease. Ulcerative colitis. Inflammatory Bowel Diseases. Biological therapies. Anti-TNF. Vedolizumab. Ustekinumab. Tofacitinib.

Anti- Melanoma Differentiation-Associated Gene 5 Antibody Positive Dermatomyositis: Recent Progress in Pathophysiology and Treatment

Purpose of ReviewAnti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a rare systemic autoimmune disease characterized by a clinically amyopathic presentation and a high-risk association with rapidly progressive interstitial lung disease. Although frequently fatal, the underlying mechanisms remain incompletely understood. This review provides a comprehensive summary of recent advances in research on MDA5-DM, aiming to deepen our understanding of its pathogenic mechanisms and to accelerate future basic research that will contribute to the development of novel therapeutic strategies.Recent FindingsRecent advancements have shed light on various aspects of this disease, including genetic and environmental factors contributing to disease susceptibility and the immunopathological processes and cytokine networks. Furthermore, significant progress has been made in understanding the pathogenicity, epitope recognition, and production mechanisms of anti-MDA5 antibodies, which have long been subjects of debate. On the therapeutic front, in addition to the conventional triple-combination regimen, emerging efficacy of JAK inhibitors and rituximab has been recognized. The development of biologics targeting lymphocytes offers additional hope for advancing therapeutic options.SummaryAdvancing our understanding of the latest pathophysiological mechanisms of MDA5-DM is expected to pave the way for the development of safer and more effective therapeutic strategies.

Successful Use of Upadacitinib, a Selective JAK Inhibitor, in the Treatment of Two Cases of Recalcitrant Chronic Uveitis

Purpose: Immunomodulatory agents, including conventional immunosuppressive treatment and biologics, are the mainstay of treating chronic uveitis. Janus kinase ( JAK) inhibitors, one of the newest biologics, have shown successful outcomes in treating autoimmune diseases such as rheumatoid arthritis and inflammatory bowel diseases by suppressing the JAK/signal transducers and transcription (STAT) pathway. We present two cases of recalcitrant chronic uveitis with significant improvement in intraocular inflammation by using upadacitinib, a selective JAK1 inhibitor. Case Reports: The first case is a 59-year-old female with HLA-B27-positive Chron’s disease and chronic anterior and intermediate uveitis who experienced an improvement in visual acuity, anterior chamber and vitreous inflammation, and cystoid macular edema on upadacitinib. The second patient is a 71-year-old female with birdshot chorioretinopathy, intolerant of initially used systemic immunosuppressive agents who showed significant improvement in vitreous inflammation, retinal phlebitis, and choroiditis after treatment with upadacitinib. Conclusion: Utilizing JAK inhibitors such as upadacitinib in treating uveitis, whether in isolated forms or in the context of systemic autoimmune diseases, may require further evaluation by controlled cohort studies.

Targeting JAK‐1 in Disseminated Cutaneous Lichen Planus

ABSTRACTWe report the case of a 63‐year‐old woman with an exuberant and recalcitrant clinical presentation of LP who had an excellent response to 200 mg/day abrocitinib, a JAK‐1 inhibitor, after failure to other commonly used therapies. The efficacy of JAK inhibitors in lichen planus is supported by small case series and isolated case reports. Further studies are necessary to confirm their full potential.

Emerging Therapeutic Approaches for Anemia in Myelofibrosis.

In this review, we highlight conventional agents and novel emerging therapeutic strategies to treat anemia in MF. Anemia is a common and challenging feature of myelofibrosis (MF). The pathobiology of anemia is multifactorial, including progressive bone marrow fibrosis, decreased erythropoiesis due to high hepcidin levels leading to iron sequestration in the reticuloendothelial system, hypersplenism, erythropoiesis inhibition by myelosuppressive JAK inhibitors (ruxolitinib, fedratinib), and others. MF-associated anemia has a negative impact on survival. Conventional agents to manage anemia include erythropoiesis-stimulating agents, danazol, corticosteroids, and immunomodulatory agents, but responses are infrequent and lack durability. Notable advancements have emerged in developing novel treatments for anemia in MF, including the regulatory approval of momelotinib (ACVR1/JAK1/2 inhibitor) in 2023 and development of novel promising agents targeting hemojuvelin and activins. Momelotinib and pacritinib (ACVR1/JAK2 inhibitor) are the preferred JAK inhibitors for patients with cytopenias (anemia, thrombocytopenia). Luspatercept and elritercept are activin receptor ligand traps, promoting erythroid maturation and late-stage erythropoiesis. Currently, luspatercept is being evaluated in a phase 3 trial (INDEPENDENCE™) for anemia in MF patients who are on a JAK2 inhibitor and require transfusions, and in a phase 2 trial (ODYSSEY) in combination with momelotinib in MF patients who are transfusion dependent, whether or not on a JAK inhibitor. Interim results of the RESTORE trial demonstrated that elritercept significantly decreased transfusions in MF patients. DISC-0974 is a first-in-class anti-hemojuvelin (positive hepcidin regulator) monoclonal antibody that decreased hepcidin expression, increased serum iron, and enhanced erythropoiesis in anemic patients with MF in a phase 1b/2 study. Burgeoning studies of novel anemia-targeted agents and combinations are significantly improving the quality of life and outcomes of patients with MF. The recent approval of momelotinib to treat MF with anemia and the emerging novel anemia-directed strategies in early and advanced clinical development have ushered in a new era in the treatment of MF-related anemia.

Herpes zoster infection in patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) are at increased risk of herpes zoster (HZ), particularly those receiving immunosuppressive treatments such as corticosteroids, thiopurines, and biologics, which elevate the likelihood of varicella-zoster virus reactivation. Despite this, vaccination rates among patients with IBD remain low. Shingrix, a recombinant zoster vaccine, is generally preferred because of its high efficacy (&gt; 90%) and safety profile in immunocompromised individuals, unlike the live attenuated zoster vaccine (Zostavax). This review underscores the importance of HZ vaccination for patients aged ≥ 50 years, as well as for younger patients receiving high-risk therapies such as JAK inhibitors. Tailored vaccination strategies based on individual risk factors, including disease severity, medication use, and ethnicity, may enhance prevention. Given the higher incidence of HZ in certain populations, such as those in Korea, vaccination recommendations should be adapted accordingly. Further research is needed to evaluate the long-term effectiveness of Shingrix in younger patients with IBD to ensure sustained protection and prevent complications, such as postherpetic neuralgia.

BDMARD drug survival in combination therapy with methotrexate in psoriatic arthritis: A systematic literature review and meta-analysis.

bDMARD drug survival in combination therapy with methotrexate in psoriatic arthritis: A systematic literature review and meta-analysis.

Chronic pruritus: a narrative review.

Chronic pruritus encompasses a manifestation of several cutaneous, allergic, infectious, neurological, psychological, and systemic conditions, whose etiological investigation and therapeutic strategy can be challenging. This comprehensive review aims to enhance the understanding of pruritus by highlighting important elements in its pathogenesis, including keratinocytes, Merkel cells and mast cells, nerve fibers, histaminergic and nonhistaminergic pathways, and the interaction of itch signals with the central nervous system. Diagnostic evaluation of chronic pruritus may require a meticulous approach, guided by the identification of skin lesions or signs/symptoms of underlying systemic diseases. A comprehensive evaluation, including a detailed medical history, thorough physical examination, and appropriate laboratory and imaging tests, often supplemented by skin biopsy and direct immunofluorescence, is essential. Treatment strategies for chronic pruritus should be individualized based on the etiology identified. General measures, such as emollients, serve as initial interventions, followed by targeted approaches. Topical corticosteroids, calcineurin inhibitors, phototherapy, and systemic immunosuppressants address cutaneous inflammation. Antihistamines, antidepressants, and immunosuppressants may be employed based on the specific etiology. Emerging therapies, including biologic drugs and JAK inhibitors, have potential in refractory cases.

Molecular heterogeneity of CD30+ peripheral T-cell lymphoma with prognostic significance and therapeutic implications: a retrospective multi-centre study.

Molecular heterogeneity of CD30+ peripheral T-cell lymphoma with prognostic significance and therapeutic implications: a retrospective multi-centre study.

Challenges Psoriasis and Its Impact on Quality of Life: Challenges in Treatment and Management.

Psoriasis, a chronic inflammatory disease affecting approximately 3% of the global population, presents complex challenges that extend beyond its physical manifestations. This comprehensive review examines the multidimensional impact of psoriasis on patients' lives, encompassing physical, psychological, and social aspects. We analyze current therapeutic approaches, from traditional systemic treatments to cutting-edge biological therapies and emerging oral medications, evaluating their efficacy, limitations, and accessibility. The review explores how disease severity correlates with quality of life measures and psychological burden, noting the high prevalence of depression (20%), anxiety (21%), and suicidal ideation (0.77%) among affected individuals. However, emerging evidence suggests that clinical severity, as measured by PASI or BSA, does not always correlate with the psychoemotional burden experienced by patients, highlighting the need for a more comprehensive assessment of disease impact. We discuss the evolution of treatment strategies, highlighting recent developments in targeted therapies, including JAK inhibitors, particularly selective TYK2 inhibitors, and PDE4 inhibitors, which offer promising alternatives to traditional treatments. Additionally, we examine the role of various assessment tools and quality of life measures in evaluating treatment outcomes. The analysis emphasizes the need for a holistic approach to patient care that integrates medical interventions with psychological support, addressing both the visible and invisible burdens of the disease. This review underscores the importance of personalized treatment strategies that consider not only clinical efficacy but also patient preferences, accessibility, and long-term safety profiles.

A Joint Decision: A Case of Obstructive Airway Disease Following Long COVID Infection While on JAK Inhibitor for Psoriatic Arthritis

A Joint Decision: A Case of Obstructive Airway Disease Following Long COVID Infection While on JAK Inhibitor for Psoriatic Arthritis

Bone marrow mesenchymal stem cells alleviate liver fibrosis after rat liver transplantation through JAK1/STAT5 pathway

ObjectiveThe effectiveness of bone marrow mesenchymal stem cells (BMSCs) in post-transplantation liver fibrosis has not been studied. The aim of this study was to investigate the effect of BMSCs on liver fibrosis and their role in the Janus-activated kinase (JAK) 1/ signal transducer and activator of transcription (STAT) 5 pathway after liver transplantation (LT).MethodsA rat model of post-LT liver fibrosis induced by cold ischemia injury was successfully established. BMSCs were injected into the rats through the portal vein. Hepatic stellate cell (HSC)-T6 were co-cultured with BMSCs in vitro after hypoxia–reoxygenation. JAK1 inhibitor Abrocitinib and JAK1 agonist RO8191 were used to study the JAK1/STAT5 signaling pathway.ResultsBMSCs significantly alleviated liver fibrosis caused by cold ischemia–reperfusion injury after rat LT in vivo. After BMSCs transplantation, the levels of JAK1 and p-STAT5 in rat liver were significantly reduced. After using Abrocitinib, the stage of liver fibrosis and the levels of collagen type I alpha 1 chain (COL1A1) and actin alpha 2 (ACTA2) decreased. After using RO8191, the stage of liver fibrosis and the levels of COL1A1 and ACTA2 increased. BMSCs significantly reduced the activation of HSC-T6 after hypoxia–reoxygenation in vitro. After co-culturing with BMSCs after HSC-T6 hypoxia–reoxygenation, the levels of JAK1 and p-STAT5 were significantly reduced. After the addition of Abrocitinib, the levels of COL1A1 and ACTA2 decreased in HSC-T6; in contrast, after adding RO8191, the levels of COL1A1 and ACTA2 increased in HSC-T6 after hypoxia–reoxygenation. After using anti-IL7 antibody or anti-IL7Rα in vivo and in vitro, the stage of liver fibrosis and the levels of COL1A1 and ACTA2 decreased as well as the phosphorylation level of STAT5.ConclusionsBMSCs alleviate hepatic cell damage, reduce hepatic cell-derived IL7, downregulate IL7R/JAK1/STAT5 in HSCs, thereby reducing HSCs’ activation and ultimately alleviating liver fibrosis after liver transplantation.

Immunological dysregulation in psoriasis: Pathophysiology, genetic influences, and emerging therapeutic strategies

The persistent, immune-mediated skin condition known as psoriasis affects millions of people globally. This study aims to present a thorough examination of the basic processes that underlie psoriasis, with an emphasis on immunological dysregulation and its consequences for the treatment of the condition. The hallmarks of psoriasis are inflammation, keratinocyte hyperproliferation, and the development of distinct, scaly plaques. The main cause of psoriasis, according to recent developments in immunology, includes both the innate and adaptive immune systems and is considered an aberrant immune response. Cytokines such as TNF-α, IL-17, and IL-23, together with T cells and dendritic cells, are key players in this dysregulation, generating a feedback loop that sustains chronic inflammation in the skin. Apart from pinpointing susceptibility loci such as PSORS1, this review highlights the role of genetic and environmental factors in the pathophysiology of psoriasis. These immunological pathways are the focus of current therapy approaches, and biologics such as TNF inhibitors, IL-17 inhibitors, and IL-23 inhibitors have demonstrated exceptional effectiveness in reducing the condition. Ongoing clinical studies are used to examine emerging treatments, such as JAK inhibitors and personalized medicine strategies. According to the review, a better knowledge of immunological dysregulation in psoriasis can result in more personalized treatment plans, which could lessen the disease's burden and enhance patients' quality of life. To create more potent and long-lasting treatment plans, greater study on the immunobiology of psoriasis is essential.

Effects of Tofacitinib Therapy on Circulating Tumour-Associated Antigens and Their Relationship with Clinical, Laboratory and Vascular Parameters in Rheumatoid Arthritis

Introduction: Tumour-associated antigens (TAA) have been implicated in cell adhesion and cancer metastasis formation, but also in inflammatory processes, such as rheumatoid arthritis (RA). There has been little information about the possible associations of TAAs with RA-related clinical and laboratory parameters, with impaired vascular pathophysiology in RA, as well as about the effects of antirheumatic drugs on TAA production. Therefore, we determined the effects of one-year tofacitinib treatment on TAA levels, as well as correlations of TAA levels with various RA-associated and vascular parameters. Patients and methods: Altogether, 26 RA patients received 5 mg bid or 10 mg bid tofacitinib treatment for 12 months. Ultrasound-based functional vascular assessments, such as common carotid intima-media thickness (ccIMT), brachial artery flow-mediated vasodilation (FMD) and carotid-femoral pulse-wave velocity (cfPWV), were determined at various timepoints. Serum concentrations of TAAs, including carcinoembryonic antigen (CEA), CA15-3, CA19-9, CA125, CA72-4, human epididymis protein 4 (HE4) and tissue polypeptide antigen (TPA), as well as various cytokines (TNF-α, IL-6, IL-8, VEGF) and PECAM-1 were determined by flow cytometry using a bead-based multiplex assay (LEGENDplex). Results: As previously determined and published, one-year tofacitinib treatment effectively suppressed disease activity and inflammation. Serum CA15-3 and HE4 levels significantly decreased both after 6 and 12 months compared to baseline (p &lt; 0.05). CA19-9 levels significantly increased both after 6 and 12 months, while CEA levels transiently increased after 6 months versus baseline (p &lt; 0.05). CA125, CA72-4 and TPA levels did not change over time. In various regression analyses, TAA levels showed variable, significant, positive associations with the 28-joint disease activity score (DAS28), CRP, ESR, RF, IL-6, TNF-α, IL-8 and PECAM-1 (p &lt; 0.05). In addition, TAAs variably correlated with ccIMT and cfPWV (p &lt; 0.05). Moreover, one-year changes in TAA levels variably correlated with DAS28, RF and some cytokines (p &lt; 0.05), as well as with changes in DAS28, HAQ, CRP, ESR, IL-6, VEGF and ccIMT from baseline to 12 months (p &lt; 0.05). Conclusions: JAK inhibition might decrease the levels of some TAAs and increase those of others. TAA levels might be associated with RA-related and vascular biomarkers. These results suggest that TAAs might play a role in inflammatory processes and vascular pathology underlying RA.