Treatment Of axSpA Research Articles

2024 Thai Rheumatism Association Guideline for the Treatment of Axial Spondyloarthritis with Biologic and Targeted Synthetic Disease-Modifying Anti-Rheumatic Drugs

Objective: To provide rheumatologists with the decisions for the appropriate and standardized treatment of patients with axial spondyloarthritis (axSpA) with biologic disease-modifying antirheumatic drugs (bDMARD) and targeted synthetic DMARDs (tsDMARD), according to current evidence and expert opinion. Materials and Methods: The development process involved 46 rheumatologist representatives from medical schools, government hospitals, and private hospitals nationwide. Relevant clinical questions related to treatment initiation criteria, administration, evaluation, monitoring, and intensive treatment options were selected. The evidence was systematically identified and summarized. Quality of evidence was evaluated and ranked according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scoring methodology. The recommendations were then proposed and voted on using the nominal group process. The input was collected from stakeholders through a public hearing. The final 13 recommendations were provided. Results: The guideline addresses the criteria for starting bDMARD/tsDMARD and details the first-line drugs for specific disease profiles, including predominantly axial involvement, predominantly peripheral joint involvement, and uveitis. It also addresses the management of patients with comorbid conditions such as tuberculosis, chronic hepatitis B, malignancy, and pregnancy. Additionally, it covers monitoring and follow-up procedures, alternative treatments for first-line treatment failures, tapering treatment after remission, and reinstitution of bDMARD/tsDMARD in case of flare-up. Conclusion: Thai Rheumatism Association has proposed a set of recommendations to outline concepts and provide guidance on the treatment of axSpA with bDMARD and tsDMARD for Thai rheumatologists.

Impact of treatments on fatigue in axial spondyloarthritis: a systematic review and meta-analysis.

Fatigue is frequent in axial spondyloarthritis (axSpA) and is difficult to improve. This systematic review aimed to assess the effects of axSpA treatment on fatigue. A systematic review following the PRISMA recommendations was performed on PubMed, Cochrane and Embase databases. We included controlled interventional studies, cohort studies conducted in patients with axSpA meeting the ASAS 2009 criteria and measuring fatigue between 12-156 weeks of treatment. We excluded studies not written in English, case reports, abstracts, systematic reviews, meta-analysis and studies with missing data. A meta-analysis was performed for anti-TNF/anti-IL17/JAK inhibitors randomized controlled trials evaluating fatigue at week 12-16. 1672 studies were identified, of which 34 were selected for analysis. Twelve studies evaluated anti-TNF with a significant reduction in fatigue measured by various scores (FACIT, MFI, NRS, VAS, FSS) in 11 studies. Among the four studies evaluating anti-IL17, three showed a reduction in fatigue, with a dose effect for secukinumab. Two studies evaluated JAK inhibitors and showed a reduction in fatigue. The meta-analysis showed no differences between the DMARDs. Concerning non-pharmacological treatments, 12 of 16 studies showed a reduction in fatigue using physical activity, cryotherapy, and magnetotherapy. Two studies showed that the addition of physical activity to anti-TNF reduced fatigue more significantly. Finally, one study showed a greater efficacy in men, and two studies suggested it as in non-radiographic form. This review shows a beneficial effect of DMARD and non-pharmacological treatment on fatigue in axSpA in short and medium terms with a greater effect when combining them.

Deciphering miRNA signatures in axial spondyloarthritis: The link between miRNA-1-3p and pro-inflammatory cytokines

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that affects the spine and sacroiliac joints. Early detection of axSpA is crucial to slow disease progression and maintain remission or low disease activity. However, current biomarkers are insufficient for diagnosing axSpA or distinguishing between its radiographic (r-axSpA) and non-radiographic (nr-axSpA) subsets. To address this, we conducted a study using miRNA profiling with massive parallel sequencing (MPS) and SmartChip qRT-PCR validation. The goal was to identify differentially expressed miRNAs in axSpA patients, specifically those subdiagnosed with nr-axSpA or r-axSpA. Disease activity was measured using C-reactive protein (CRP) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Radiographic assessments of the cervical and lumbar spine were performed at baseline and after two years. Out of the initial 432 miRNAs, 90 met the selection criteria, and 45 were validated out of which miR-1-3p was upregulated, whereas miR-1248 and miR-1246 were downregulated in axSpA patients. The expression of miR-1-3p correlated with interleukin (IL)-17 and tumour necrosis factor (TNF) levels, indicating its significant role in axSpA pathogenesis. Although specific miRNAs distinguishing disease subtypes or correlating with disease activity or spinal changes were not found, the study identified three dysregulated miRNAs in axSpA patients, with miR-1-3p linked to IL-17 and TNF, underscoring its pathogenetic significance. These findings could help improve the early detection and treatment of axSpA.

Axial Spondyloarthritis Treatment Recommendations in 2024: Where Are We Now?

As 2024 continues to evolve, so do treatment recommendations for the management of spondyloarthritis (SpA), including ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). From a Canadian perspective, we eagerly await the publication of the Canadian Rheumatology Association (CRA)/Spondyloarthritis Research Consortium of Canada (SPARCC) Living Treatment Recommendations for the Management of Axial Spondyloarthritis (axSpA), currently in press. Until these recommendations for axSpA treatment with a Canadian perspective arrive – where are we now?

Treatment of spondyloarthritis with disease-modifying anti-rheumatic drugs during pregnancy and breastfeeding: comparing the recommendations and guidelines of the principal societies of rheumatology.

This paper aims to provide an overview of the use of treatments available for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) during pregnancy and breastfeeding, according to current national recommendations and international guidelines, as well as data on the impact on pregnancy outcomes of paternal exposure to treatment. We performed a narrative review of national and international recommendations and guidelines on the reproductive health of patients suffering from rheumatic diseases. The last updated recommendations and guidelines were considered source data. We reported updated information regarding the treatment of axSpA and PsA with nonsteroidal anti-inflammatory drugs, intra-articular glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and targeted synthetic DMARDs during the preconception period, pregnancy, and breastfeeding, as well as data related to paternal exposure. We highlighted any medications that should be discontinued and/or not used in the reproductive age group and also treatments that may be continued, avoiding the withdrawal of drugs that can be used in the different phases, thus preventing the risk of increasing disease activity and flares before, during, and after pregnancy in SpA patients. The best management of pregnancy in patients with SpA is based on knowledge of updated drug recommendations, a careful and wise evaluation of the risks/benefits of starting or continuing treatment from the SpA diagnosis in a woman of childbearing age through pregnancy and lactation, and sharing therapeutic choices with other healthcare providers (in particular, gynecologists/obstetricians) and the patient.

The Role of Corticosteroid Injections in the Treatment of Sacroiliitis: A Narrative Review.

Axial spondyloarthritis (axSpA) is a chronic rheumatic, musculoskeletal, inflammatory disease with a propensity to present as sacroiliitis, which manifests as low back, buttock, or thigh pain. Effective primary management of axSpA requires a comprehensive approach specific to each patient and disease severity. Non-pharmacological measures form the cornerstone of treatment. With refractory disease, management also consists of local periarticular and intraarticular injections. The use of sacroiliac joint (SIJ) corticosteroid injections for the treatment of axSpA and localised inflammation, however, is a continuously burgeoning management option. This narrative review aims to present consolidated findings and summarise previously unreferenced or recently available evidence regarding corticosteroid injections to the SIJ for treating sacroiliitis and axSpA. A comprehensive literary review with the following electronic databases was searched: MEDLINE via PubMed, Web of Science, Cochrane Library, and EMBASE. The initial search yielded a total of 126 references. After duplicates were removed and the remainder analysed for inclusion criteria, 7 studies were included. To stratify each study, injection methodology and characteristics were defined. The use of SIJ corticosteroid injections can be an appropriate and effective treatment option for refractory axSpA. The studies presented in this review reported a general trend towards a reduction in pain severity after SIJ corticosteroid injections. Because of the complexity and heterogeneity of the anatomy of the SIJ, image guidance is recommended when performing SIJ injections. Image-guided injections seem to produce better outcomes when compared to anatomic landmark-guided injections.

Axial spondyloarthritis—current aspects

Axial spondyloarthritis (axSpA) is a frequent inflammatory rheumatic disease mainly affecting the axial skeleton causing inflammatory back pain. If chronic inflammation persists new bone formation may occur possibly leading to irreversible spinal stiffness. The disease has a strong genetic background with HLA-B27 as the major factor. For diagnostic purposes, imaging is of critical importance—especially conventional radiography and magnetic resonance imaging (MRI). While the former has advantages in the detection of bony changes such as the syndesmophytes, MRI is used to detect axial inflammation but also erosions in the sacroiliac joint. Treatment follows the treat-to-target strategy starting with non-steroidal anti-inflammatory drugs (NSAIDs) in the first line, and later, if high disease activity persists, therapy with biologic disease modifying anti-rheumatic drugs (bDMARDs) is according to international recommendations indicated. For the treatment of axSpA, important targets such as tumor necrosis factor alpha (TNFα) and interleukin (IL)-17 have been identified, and several of their inhibitors (i) including some biosimilars for the former have been approved. Recently, also inhibition of Janus kinases was shown to be efficacious. There is evidence that long term inhibition of inflammation with TNFi can reduce bone formation.

Resolution of the Expert Council “New approaches to the treatment of axial spondyloarthritis”

On 30 May, 2024, an expert meeting was held to update the approaches for the treatment of axial spondyloarthritis (axSpA). A new approach to the treatment of axSpA was considered, which consists of depleting autoreactive TRBV9+ T- lymphocytes by introducing a monoclonal antibody – the drug seniprutug. The value of the drug seniprutug in the treatment of the disease was discussed and key aspects for the incorporation of the drug seniprutug into real-world clinical rheumatological practice were agreed.

Literature review of non-pharmacological treatment for patients with axial spondyloarthritis.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disorder affecting the sacroiliac joints and axial spine. Along with pharmacotherapy, non-pharmacological interventions for axSpA are crucial and constitute the cornerstone of treatment. Here, we review the evidence for non-pharmacological treatment of axSpA as a basis for the 2023 Korean treatment recommendations for patients with axSpA. The effectiveness of the core non-pharmacological approaches, such as education, smoking cessation, and exercise, has been reaffirmed. High-quality research on surgical treatment is limited. However, total hip replacement is advised in patients with ongoing pain or disability and visible structural damage to the hip on imaging. Urgent spinal intervention should be considered in cases of acute spinal pain with neurological deficiency or concurrent unstable fractures. Evidence for complementary therapies, including spas and acupuncture, remains insufficient.

The failure of biological treatment in axial spondyloarthritis is linked to the factors related to increased intestinal permeability and dysbiosis: prospective observational cohort study

BackgroundA significant number of patients with axial spondyloarthritis (axSpA) do not respond to biological therapy. Therefore, we decided to investigate the specificity of this group of patients and, in particular, whether haptoglobin (Hp), its polymorphism and zonulin, in addition to other clinical features, are predictors of poor response to biological treatment.Methods48 patients with axSpA who were unsuccessfully treated with standard drugs were converted to biological treatment, and from this time on, a 12-week follow-up was started to assess the failure of biological treatment (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decrease < 2 points). Predictors of treatment failure were identified using logistic regression analysis.Results21% of subjects had biological treatment failure. Patients who had a higher zonulin level, a history of frequent infections, were older, had inflammatory bowel disease (IBD), had a lower Hp level at the time of inclusion in biological therapy showed an increased risk of treatment failure.ConclusionsThe results of the study support the hypothesis that the effectiveness of biological treatment of axSpA is limited by changed microbiota and intestinal epithelial barrier dysfunction, as an increased risk of biological treatment failure was observed in patients who were older, had higher zonulin level, IBD and repeated courses of antibiotics due to frequent infections. Therefore, starting biological treatment should be followed by reducing intestinal permeability and regulating the disturbed gut microbiome.

Artificial intelligence and machine learning in axial spondyloarthritis.

To evaluate the current applications and prospects of artificial intelligence and machine learning in diagnosing and managing axial spondyloarthritis (axSpA), focusing on their role in medical imaging, predictive modelling, and patient monitoring. Artificial intelligence, particularly deep learning, is showing promise in diagnosing axSpA assisting with X-ray, computed tomography (CT) and MRI analyses, with some models matching or outperforming radiologists in detecting sacroiliitis and markers. Moreover, it is increasingly being used in predictive modelling of disease progression and personalized treatment, and could aid risk assessment, treatment response and clinical subtype identification. Variable study designs, sample sizes and the predominance of retrospective, single-centre studies still limit the generalizability of results. Artificial intelligence technologies have significant potential to advance the diagnosis and treatment of axSpA, providing more accurate, efficient and personalized healthcare solutions. However, their integration into clinical practice requires rigorous validation, ethical and legal considerations, and comprehensive training for healthcare professionals. Future advances in artificial intelligence could complement clinical expertise and improve patient care through improved diagnostic accuracy and tailored therapeutic strategies, but the challenge remains to ensure that these technologies are validated in prospective multicentre trials and ethically integrated into patient care.

How to Monitor Disease Activity of Axial Spondyloarthritis in Clinical Practice.

Treatment guided by periodic and quantitative data assessment results in better outcomes compared to using clinical gestalt. While validated generic as well as specific disease activity measures for axial spondyloarthritis (axSpA) are available, there is vast scope to improve their actual utilization in routine clinical practice. In this review, we discuss available disease activity measures for axSpA, describe results from the survey conducted among general rheumatologists as well as Spondyloarthritis Research and Treatment Network (SPARTAN) members about disease activity measurement in daily practice, and discuss ways to improve axSpA disease activity using technological advances. We also discuss the definitions of active disease and target for the treatment of axSpA. The 2019 American College of Rheumatology (ACR)/Spondylitis Association of America (SAA)/Spondyloarthritis Research and Treatment Network (SPARTAN) axSpA treatment guidelines conditionally recommend the regular monitoring of disease activity using a validated measure such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) or Ankylosing Spondylitis Disease Severity Index (ASDAS). Assessment of Spondyloarthritis International Society (ASAS)-European Alliance of Associations for Rheumatology (EULAR) guidelines recommend ASDAS as the most appropriate instrument for the assessment of disease activity, preferably calculated using C-reactive protein (CRP). ASAS has selected a core set of variables which were updated recently and have been endorsed by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group in order to bring homogeneity in assessment of axSpA. In a recent study, Patient-Reported Outcomes Measurement Information System (PROMIS®) measures were able to discriminate inactive, moderate, and high-very high ASDAS activity groups. A newly developed semi-objective index P4 (pain, physical function, patient global, and physician global) correlates well with BASDAI and ASDAS in axSpA and can also be used for other rheumatic diseases in busy clinical practices. Regular disease activity monitoring is critical for long-term management of axSpA and shared decision-making. The integration of electronic health records and smart devices provides a great opportunity to capture patient-reported data. Automated capture of electronic patient-reported outcome measures (ePROMs) is a highly efficient way and results in consistent regular monitoring and may improve the long-term outcomes. While currently used measures focus only on musculoskeletal symptoms of axSpA, a composite disease activity measure that can also incorporate extra-articular manifestations may provide a better assessment of disease activity.

Population pharmacokinetics and exposure-response analyses for efficacy and safety of upadacitinib in patients with axial spondyloarthritis.

Upadacitinib is an orally administered, selective, Janus kinase inhibitor that is approved for several auto-immune conditions, such as axial spondyloarthritis, an inflammatory rheumatic disease that includes ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). The approvals of upadacitinib for the treatment of AS and nr-axSpA were based on the safety and efficacy data for upadacitinib 15 mg once-daily compared to placebo from the SELECT-AXIS 1 and SELECT-AXIS 2 studies. Population pharmacokinetic analyses based on data from 244 patients with axSpA showed that the pharmacokinetics of upadacitinib were comparable in subjects with AS and nr-axSpA. Exposure-response relationships were characterized for key efficacy and safety end points using data from 482 patients with axSpA. The exposure-response analyses for efficacy based on Assessment of SpondyloArthritis International Society (ASAS)20 and ASAS40 responses at week 14, showed a clear differentiation from placebo with no evidence of increased responses with increasing upadacitinib plasma exposures. There were no clear exposure-response trends observed for safety end points that included serious infections, herpes zoster, pneumonia, lymphopenia (grade ≥3), neutropenia (grade ≥3), or a greater than 2 g/dL decrease in hemoglobin from baseline through week 14. The exposure-response analyses for efficacy and safety presented here supported the favorable benefit-risk profile with the use of upadacitinib 15 mg once-daily for the treatment of axSpA.

Unlocking JAKi Potential: Redefining Axial Spondyloarthritis Treatment Paradigms

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that primarily affects the axial skeleton, encompassing both radiographic and non-radiographic forms. The disease is characterized by chronic back pain and spinal stiffness, which are the most common symptoms. However, it often includes peripheral manifestations and extra-musculoskeletal symptoms as well, making the clinical presentation quite diverse. JAK inhibitors work by blocking the intracellular signaling pathways of several proinflammatory cytokines, which play a crucial role in the pathogenesis of inflammatory diseases. Given their proven efficacy in managing rheumatoid arthritis and their ability to mediate the signaling of cytokines involved in the pathogenesis of axSpA, JAK inhibitors have been the subject of numerous clinical trials in this context. The Assessment of SpondyloArthritis international Society and the European Alliance of Associations for Rheumatology (ASAS-EULAR) joint recommendations provide comprehensive guidance for the management of axSpA in 2022. The guideline introduced the use of Janus kinase inhibitors (JAKi), as a completely new drug class in the treatment landscape, with efficacy demonstrated in radiographic axSpA. JAKi was recommended, as a means to treatment intensification, in axSpA patients with persistently high disease activity despite conventional treatment. Since then, more trial data results have been released, showing efficacy in non-radiographic axSpA population as well. In this lecture, Professor Östör will delve into the critical role of shared decision-making in the management of axial spondyloarthritis. He will emphasize the importance of tailoring treatment plans to individual patient preferences and clinical profiles, a practice that is increasingly recognized as vital in achieving optimal outcomes. By examining current international guidelines and the latest study data, Professor Östör will provide a comprehensive overview of the benefit-risk profile of Upadacitinib in the treatment of axSpA. Professor Östör will also share his clinical experience with Upadacitinib, discussing various case studies to illustrate its application in real-world settings. This will include an exploration of how patient preferences and clinical profiles can influence treatment decisions, ensuring a personalized approach to managing this complex disease.

Precision medicine in axial spondyloarthritis: current opportunities and future perspectives.

Axial spondyloarthritis (axSpA) is a complex disease characterized by a diverse range of clinical presentations. The primary manifestation is inflammatory lower back pain, often accompanied by other clinical manifestations such as peripheral arthritis, enthesitis, uveitis, psoriasis, and inflammatory bowel disease. However, the presentation of axSpA can vary widely among patients. Despite extensive research, the precise pathogenesis of axSpA remains largely unknown. The lack of complete understanding poses challenges in subgrouping the disease, developing specific treatment approaches, and predicting treatment response. In this review, we will explore the limitations in diagnosing and treating axSpA. In addition, we will examine the current knowledge and potential opportunities provided by various omics and technological advancements in enhancing the diagnosis and personalized treatment of axSpA.

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

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 &lt; 0.001), with this reduction being sustained after 12 months (1.6 vs. 1.9, p &gt; 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 &gt; 0.05). No significant differences were found between biologic-naive and biologic-experienced patient subgroups (84.2% vs. 78.3%, p &gt; 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 &lt; 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.

Korean treatment recommendations for patients with axial spondyloarthritis.

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5-12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13-16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

Looking through the window of opportunity in axial spondyloarthritis?

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that affects the spine and sacroiliac joints, that can lead to irreversible structural damage. Early detection and timely intervention are crucial for preventing long-term structural damage, improving quality of life, and reducing the burden of the disease. The concept of a window of opportunity suggests that an early intervention in the reversible stage of the disease can lead to improved long-term outcomes. However, it is unclear whether this concept applies in axSpA. Recent advances in axSpA management, including the use of diagnostic techniques such as magnetic resonance imaging as well as the use of advanced therapies, have shown promise in improving outcomes. However, studies investigating the potential window of opportunity in axSpA by assessing the impact of an early treatment on clinical outcomes have yielded inconclusive results. One of the reasons behind this is the lack of a standardized definition of early axSpA. The Assessment of Spondyloarthritis International Society (ASAS)-SPEAR (SPondyloarthritis EARly) project has set the ground for it by working on a consensus definition of early axSpA. Randomized controlled trials specifically focused on the comparison between treating axSpA in the early and late stages of the disease and using the standardised definition of early axSpA are essential to understand better the potential benefits of an early treatment on clinical outcomes. Additionally, it would be relevant to assess the long-term outcomes of early axSpA treatment, especially regarding structural damage, to better grasp the concept of the window of opportunity in axSpA.

JAK Inhibitors for the Treatment of Axial Spondyloarthritis.

Axial spondyloarthritis (axSpA) is a chronic disease characterized by inflammation and new bone formation that causes pain and results in functional impairment and long-term disability. Biologic agents targeting TNFα or IL-17 have been the mainstay of treatment for patients with axSpA and an inadequate response to nonsteroidal anti-inflammatory drugs. However, a proportion of axSpA patients do not respond adequately to those drugs either, creating the need to target alternative disease pathways. Janus kinase (JAK) inhibitors (JAKis) are a group of targeted synthetic disease-modifying anti-rheumatic drugs that block the intracellular signalling pathway of several proinflammatory cytokines. Given their efficacy in the management of rheumatoid arthritis and that JAKs mediate the signalling of cytokines involved in the pathogenesis of axSpA as well, JAKis have been successfully tested in a number of clinical trials in axSpA, which has led to the approval of two compounds, tofacitinib and upadacitinib for the treatment of the disease. Data from new clinical trials, long-term extensions of completed trials, and real-life observational studies that continuously emerge will shape the efficacy and safety profile and ultimately the place of JAKis in the treatment of AxSpA.

Knowledge mapping of biological disease-modifying anti-rheumatic drugs for axial spondyloarthritis: a bibliometric study.

Various biological disease-modifying anti-rheumatic drugs (bDMARDs) have been applied for treating axial spondyloarthritis (axSpA). However, there is a glaring absence of a bibliometric analysis on bDMARDs against axSpA. Articles related to use of bDMARDs in treating axSpA published from 2004 to 2022 were searched from the Web of Science Core Collection. VOS viewer 1.6.18 and CiteSpace 6.1.R2 were used to analyze and visualize the quantity and citations of publications, as well as to identify "research hotspots" and trends in this field. BibExcel version 1.0.0 and gCLUTO version 1.0 were used to build matrices for bi-clustering analysis. A total of 2546 articles referring to bDMARDs for treatment of axSpA were included in this bibliometric analysis. Overall, the number of publications has been increasing steadily annually. The USA (23.21%, 591 publications) ranked first with the largest output of papers, followed by Germany, and the Netherlands. Rheumazentrum Ruhrgebiet ranked first as the most frequent publisher (119 articles). Annals of the Rheumatic Diseases published the most documents (6.76%, 172 publications) in this field. The predominant hotspots have been "tuberculosis," "IL-17," and "quality of life" in the field until 2020. Since 2015, "biosimilar pharmaceuticals" has retained the popularity. Current research hotspots are "spinal radiographic progression," Janus kinase (JAK) inhibitors, and adverse events (AEs). Machine learning has become popular gradually. Globally, there has been a steady increase in the number of studies on bDMARDs use against axSpA. JAK inhibitors, spinal radiographic progression, biosimilar pharmaceuticals, and AEs are current research hotspots. Machine learning is emerging research hotspots and trends in this field.