Ankylosing spondylitis (AS) is a rheumatic and autoimmune disease associated with a chronic inflammatory response, characterized by pain, stiffness, or limited movement of the spine and sacroiliac joints, and in severe cases, joint deformity, destruction, and even lifelong disability. In the past 20 years, a large number of clinical studies on AS have been published, based on this, domestic scholars have summarized the research status and global trends related to AS clinical trials in the past 20 years through bibliometric analysis, so as to help clinicians better understand the relevant research.
Research Methods:
Methods
The Web of Science Core Collection database was searched for literature related to clinical trials in AS published between January 2003 and June 2023. Bibliometric analysis and web visualization were performed using CiteSpace, VOSviewer, and the bibliometric online analysis platform (https://bibliometric.com), including the number of documents, citations, countries, institutions, journals, authors, references, and keywords.
Findings:
Results
Number of posts
The number of publications related to AS clinical trials is increasing year by year
The study resulted in the inclusion of 1212 articles in 201 journals in 65 countries, and the number of articles related to AS clinical trials is increasing every year. In 2018, 83 papers were published and cited 4,371 times, reaching a peak. The literature included in this study was cited 56425 times, with an average citation frequency of 46.33 times. Between 2003 and 2023, the academic field H-index is 114 (Figure 1).
Fig. 1 The number of publications related to AS clinical trials in an annual year
Issuing countries and institutions
The United States and Freie Universität Berlin are the countries and institutions that publish the most AS papers, respectively
Table 1 lists the top 10 countries and institutions with the most published papers in the field of AS clinical trials, as well as their total number of published papers (NP), total number of citations (NC), average number of citations (AC), and H-index score.
Table 1 Publications in the field of AS clinical trials in different countries and institutions
In this field, the United States had the largest number of published papers (NP=385, 21.28%), followed by Germany (NP=318, 17.58%). The most cited country was Germany (27,066), followed by the United States (24,454) and the Netherlands (19,034). The most cited country was the Netherlands (AC=88.94), followed by France (AC=85.31) and Germany (AC=85.11). The number of articles published in China in the field of AS is about the same as that of Italy and Belgium, but the NC and AC of Chinese articles are relatively low.
The 10 most influential institutions in this field are shown in Table 1, with the university with the highest NP value being Freie Universität Berlin (NP=184), followed by the Charité University of Berlin (NP=179) and the Humboldt-Universität Berlin (NP=179). Of the top 10 institutions, the top five are all from Germany, followed by three from France and two from the Netherlands.
Figure 2 Proportion of publications in the field of AS clinical trials in different countries
Fig. 3 Cooperation in the field of AS clinical trials in different countries
More
Author
Desiree van der Heijde is the author with the highest number of published papers and co-citations
Table 2 lists the top 10 authors and co-cited authors who contributed the most to AS clinical trial research, with Desiree Van der Heijde topping the list. Overlay visual analysis revealed that Sieper and Braun were the early authors most closely associated with clinical trial research. Van Der Heijde is the most influential author of the interim period, while Atul Deodhar and Baraliakos are the emerging authors of clinical trial studies published in recent years. The first three TLS-based authors were Van der Heijde (TLS = 2933), Sieper (TLS = 2835), and Braun (TLS = 2254).
Table 2 The top 10 authors and co-cited authors who contributed the most to AS clinical trial research
Fig.4 Author citation analysis overlay visualization based on VOSviewer
Note: The purple nodes represent authors who participated in early research in the field, while yellow nodes represent authors who participated in later research in the field
Publish a magazine
发表和被引用文章最多的杂志是《Annals of The Rheumatic Diseases》
发表论文最多的期刊是Annals of The Rheumatic Diseases (n=137, 23.50%)，同时该期刊也是被引最多次的期刊(NC=15,592)，其次是Journal of Rheumatology (n=111,10.04%)和Rheumatology(n=64,10.98%)。
Study drug
Seculumab and TNF inhibitors have the highest citation rate in the AS clinical trials
In order to clarify the research direction and focus in this field, the authors counted the top 10 most cited articles in AS clinical trials. According to the data in Table 3, secukinumab (interleukin-17A inhibitor) AS has the highest citation rate in clinical trial-related literature, followed by TNF inhibitors.
Table 3 The top 10 most cited articles in AS clinical trials
Research hotspots
“inflammation”，“psoriatic arthritis”和“axial spondyloarthritis”可能是当前AS临床试验研究热点和未来趋势
Table 4 shows the top 10 keywords in the field of AS clinical trials: "double-blind", "rheumatoid arthritis", "efficacy", "placebo-controlled trial", "infliximab", "etanercept", "psoriatic arthritis" and "therapy" It is the hottest keyword in this field at the moment.
Table 4 The top 10 keywords with the highest frequency in the field of AS clinical trials
The analysis of keywords overlaid (Figure 5) showed that the keywords gradually changed from "necrosis factor alpha", "methotrexate", "sulfasalazine", and "tumor necrosis factor" to "inflammation", "psoriatic", "arthritis", and "axial" over time spondyloarthritis" and "remission" (purple nodes indicate early hotspots, yellow nodes indicate emerging hotspots). The authors analyzed the top 25 keywords with the strongest citations (Figure 6) and showed that the keyword "axial spondyloarthritis" was the most explosive (16.3 in intensity) and the longest-lasting in terms of outbreak duration (2003-2006). The earliest keyword was "necrosis factor alpha", while "inflammation", "risk", and "improvement" are the latest keywords in recent years. As can be seen from Figures 5 and 6, "inflammation", "psoriatic arthritis" and "axial spondyloarthritis" are the most frequent keywords in recent times, and these keywords may represent the current hotspots and future trends in AS clinical trial research.
Fig.5 Visualization of keyword overlay in the field of AS clinical trials
Fig.6 The top 25 keywords with the strongest outbreaks are cited
More
Research Discussion
Discussion
Over the past two decades, the publication of literature in the field of AS clinical trials has shown a steady year-on-year upward trend (mainly divided into two phases), which began to level off after the surge in 2005 and 2014, respectively, which may be related to the approval of TNF inhibitors and IL-17A inhibitors for clinical use. The top 10 citations were published in top journals in the field of rheumatology and immunology, and most of them were published by Van Der Heijde and Sieper's team.
Most of the literature involved in this study focused on clinical trials of TNF inhibitors for the treatment of AS, and the research time was mostly concentrated in the early stages, indicating that TNF inhibitors such as adalimumab, infliximab and golimumab are more effective and better tolerated than traditional rheumatic immune drugs such as non-steroidal anti-inflammatory drugs and glucocorticoids in most AS patients. Over the past decade, most of the most cited studies have focused on the IL-17A inhibitor secukinumab.
IL-17 is a pro-inflammatory cytokine primarily derived from TCD4+ T cells and helper T subtype 17 cells, and has been implicated in stromal destruction, tissue inflammation, and autoimmunity. Patients with AS had a significant increase in the number of TH17 cells, as well as a significant increase in serum and joint IL-17, compared to healthy subjects. There are 6 members of the IL-17 family (A to F), and IL-17A was the first member of the study, and IL-17A was found to increase the expression of NF-kB ligand receptor activator in osteoblasts, suggesting that IL-17A plays an important role in bone remodeling. More studies have found that IL-17A can also increase the expression of adhesion molecules in endothelial cells by stabilizing TNF-induced chemokines, thereby promoting granulocyte aggregation towards the site of inflammation. IL-17 plays an important role in immune system diseases as a potential therapeutic target. In addition, since the clinical approval of IL-17A inhibitors, no significant adverse reactions and infections have been found in patients. These results suggest that in-depth excavation of IL-17 has increasingly become the focus of AS research.
This study also showed that rheumatoid arthritis and psoriatic arthritis are the two diseases most closely related to AS, and their treatments are similar. Research in AS clinical trials has shifted from focusing on drug effectiveness to focusing on drug tolerance. Keyword outbreak analysis, "inflammation", "risk" and "improvement" are emerging keywords in recent years, which indicates that clinicians are now more focused on the long-term quality of life of patients. "IL-17" and "secukinumab" will be the keywords for future outbreaks in this field.
Based on the above analysis of each keyword, it can be seen that the research hotspots in the field of AS clinical trials will continue to focus on the development of immunotherapy drugs in this disease field in the future. In addition, researchers will continue to focus on the long-term effectiveness of drugs in improving patients' clinical symptoms and reducing complications, as well as reducing the rate of AS recurrence, so that patients can achieve a higher quality of life.
Conclusions of the study
Conclusion
This study is the first bibliometric analysis in the field of AS clinical trials, which is helpful to clarify the current research hotspots and directions in this field, predict future research progress, and provide valuable information for future clinicians. Future studies should continue to explore TNF and interleukin inhibitors, as well as placebo-controlled trials.
Bibliography:
Zhang W, Li M, Li X, Wang X, Liu Y, Yang J. Global trends and research status in ankylosing spondylitis clinical trials: a bibliometric analysis of the last 20 years. Front Immunol. 2024 Jan 8;14:1328439. doi: 10.3389/fimmu.2023.1328439. PMID: 38288126; PMCID: PMC10823346.
Yimaitong is a professional online doctor platform, and the mission of the platform is to "sense the pulse of the world's medicine and help China's clinical decision-making". Yimaitong has a series of products such as "Clinical Guidelines", "Medication Reference", "Medical Literature King", "Yizhiyuan", "eYantong" and "ePulse", which fully meet the needs of medical workers in clinical decision-making, obtaining new knowledge and improving scientific research efficiency.