Janus Kinase Inhibitors: A New Tool for the Treatment of Axial Spondyloarthritis

Paroli, Marino; Caccavale, Rosalba; Paroli, Maria Pia; Spadea, Luca; Accapezzato, Daniele

doi:10.3390/ijms24021027

Cited by 7 publications

(6 citation statements)

References 112 publications

(133 reference statements)

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“…Upadacitinib is considered for the treatment of axSpA in our real-world clinical setting relatively late after the diagnosis, with similar delays observed in bionaive patients and those with previous bDMARDs treatment failure. Similar findings are reported by other authors who observe that there is a period of 5 to 7 years between the onset of symptoms and the diagnosis of axSpA, and treatment initiation occurs even later [11].…”

Section: Discussionsupporting

confidence: 91%

Upadacitinib in real clinical practice: new horizons in the treatment of axial spondyloarthritis

Shivacheva,

Dimova,

Simeonova

et al. 2023

RBJ

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Introduction. Axial spondyloarthritis (axSpA) is an inflammatory disorder affecting the axial skeleton, accompanied by pain, restricted mobility, and other symptoms. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a metric expressing disease activity, assessing inflammation and symptoms. In clinical trials, Upadacitinib has demonstrated reduced axSpA activity, but real-world evidence remains limited. Objective. The objective of this study is to evaluate the therapeutic effectiveness of Upadacitinib in axSpA by analysing its impact on symptoms, activity, and inflammatory markers in real clinical practice. Additional goals include comparing outcomes between biologic-naive and biologic-experienced patients, as well as assessing the influence of radiographic stage on Upadacitinib's therapeutic response. Methods. Sixty-four patients with axSpA were enrolled in Upadacitinib treatment. Among them, 42 were evaluated after 6 months and 13 after 12 months of therapy. ASDAS was assessed at various time points and analyzed based on prior experience with biologic drugs and radiographic stage of sacroiliitis. Results. A notable reduction in mean ASDAS values was observed after 6 months of Upadacitinib treatment (3.5 vs. 1.9, p < 0.001), with this reduction being sustained after 12 months (1.6 vs. 1.9, p > 0.05). A substantial proportion of patients (80.9%) achieved ASDAS values below 2.1 after 6 months, and this achievement was maintained after 12 months (84.6%, p > 0.05). No significant differences were found between biologic-naive and biologic-experienced patient subgroups (84.2% vs. 78.3%, p > 0.05). Similar trends were observed in the analysis of other parameters such as BASDAI, fatigue, pain, CRP, haemoglobin, and ESR. Upadacitinib increased the number of patients with low disease activity regardless of radiographic stage after 6 and 12 months (23.7 vs. 83.3% and 5.7 vs. 85.3%, p < 0.001). Conclusion. Upadacitinib proves to be effective in axSpA treatment. Regardless of demographic, clinical, and radiographic disease characteristics, as well as "biologic-naive/biofailure" status, Upadacitinib leads to ASDAS improvement after 6 and 12 months of treatment. This medication represents an effective tool in real-world clinical practice for controlling axSpA activity.

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Section: Discussionsupporting

confidence: 91%

Upadacitinib in real clinical practice: new horizons in the treatment of axial spondyloarthritis

Shivacheva,

Dimova,

Simeonova

et al. 2023

RBJ

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“…Notably, TNF-α is involved in the pathogenesis of nr-axSpA and does not directly stimulate the JAK/STAT pathway [56]. However, IFN-γ and IL-12 signaling through the JAK1/JAK2 and JAK2/TYK2 combinations are critical to the Th1 cell response and indirectly regulate the production of TNF-α by macrophages [55,57].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of TNF-α Inhibitors in the Treatment of nr-axSpA: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials

Shentu,

Sha,

et al. 2024

Int Arch Allergy Immunol

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Introduction: A growing number of randomized controlled trials (RCTs) have demonstrated the effectiveness of tumor necrosis factor-α (TNF-α) inhibitors in treating non-radiographic axial spondyloarthritis (nr-axSpA). This study aimed to evaluate the efficacy of TNF-α inhibitors in the treatment of nr-axSpA. Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were systematically searched for relevant RCTs using specific keywords up to June 2023. The primary outcome was the proportion of patients who achieved Assessment in SpondyloArthritis international Society 40% (ASAS40). Secondary outcomes included ASAS20, Bath Ankylosing Spondylitis Disease Activity Index 50% (BASDAI50), ASAS partial remission, and ASAS5/6. Results: A total of eight RCTs involving 1,376 patients were included. Patients receiving anti-TNF therapy exhibited a higher rate of ASAS40 (pooled RR = 2.36; 95% CI: 1.63–3.42; p < 0.001). In addition, the TNF-α inhibitor group showed higher BASDAI50 rates (pooled RR = 2.06; 95% CI: 1.48–2.89), ASAS20 rates (pooled RR = 1.48; 95% CI: 1.31–1.67), ASAS partial remission rates (pooled RR = 2.33; 95% CI: 1.58–3.43), and ASAS5/6 rates (RR = 3.46; 95% CI: 2.05–5.83) than the placebo group. Conclusion: The TNF-α inhibitors were effective in treating nr-axSpA.

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“…On the other hand, many researchers are investigating the role of environmental factors, such as pollution and diet, in AD and inflammation in the brain [ 103 ]. Furthermore, researchers are exploring new targets for anti-inflammatory therapies, such as NLRP3 inflammasomes, as NLRP3 has been linked to the generation of pro-inflammatory cytokines in AD, and anti-inflammatory drugs such as Janus kinase (JAK) inhibitors, which are being tested in clinical trials [ 68 , 104 ]. Epidemiological evidence has linked to a reduced AD risk during the utilization of anti-inflammatory drugs [ 3 ].…”

Section: Role Of Inflammation In Admentioning

confidence: 99%

Alzheimer's Disease Puzzle: Delving into Pathogenesis Hypotheses

Nasb¹,

Wan²,

Chen³

2024

Aging dis

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Alzheimer's disease (AD) is a prevalent neurodegenerative disease characterized by both amnestic and non-amnestic clinical manifestations. It accounts for approximately 60-70% of all dementia cases worldwide. With the increasing number of AD patients, elucidating underlying mechanisms and developing corresponding interventional strategies are necessary. Hypotheses about AD such as amyloid cascade, Tau hyper-phosphorylation, neuroinflammation, oxidative stress, mitochondrial dysfunction, cholinergic, and vascular hypotheses are not mutually exclusive, and all of them play a certain role in the development of AD. The amyloid cascade hypothesis is currently the most widely studied; however, other hypotheses are also gaining support. This article summarizes the recent evidence regarding major pathological hypotheses of AD and their potential interplay, as well as the strengths and weaknesses of each hypothesis and their implications for the development of effective treatments. This could stimulate further studies and promote the development of more effective therapeutic strategies for AD.

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Janus Kinase Inhibitors: A New Tool for the Treatment of Axial Spondyloarthritis

Cited by 7 publications

References 112 publications

Upadacitinib in real clinical practice: new horizons in the treatment of axial spondyloarthritis

Upadacitinib in real clinical practice: new horizons in the treatment of axial spondyloarthritis

Efficacy of TNF-α Inhibitors in the Treatment of nr-axSpA: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials

Alzheimer's Disease Puzzle: Delving into Pathogenesis Hypotheses

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