Therapeutic Advances in Musculoskeletal Disease最新文献

{"title":"Impact of bimekizumab and certolizumab pegol on efficacy, safety and osteoblastic activity in radiographic axial spondyloarthritis: results from a phase IIa, multicentre, randomised, double-blind, exploratory study with PET-CT imaging.","authors":"Xenofon Baraliakos, Jerney de Jongh, Denis Poddubnyy, Gerben J C Zwezerijnen, Robert Hemke, Sophie Glatt, Stevan Shaw, Lucian Ionescu, Assem El Baghdady, Joanne Mann, Ralph Paul Maguire, Tom Vaux, Natasha de Peyrecave, Marga Oortgiesen, Dominique Baeten, Conny van der Laken","doi":"10.1177/1759720X241293944","DOIUrl":"https://doi.org/10.1177/1759720X241293944","url":null,"abstract":"<p><strong>Background: </strong>The efficacy and safety of bimekizumab (BKZ), an inhibitor of interleukin (IL)-17F in addition to IL-17A, has been established in axial spondyloarthritis (axSpA). Early assessment of new bone formation is possible using ¹⁸F-fluoride positron emission tomography-computerised tomography (PET-CT) imaging to quantitatively monitor osteoblastic activity.</p><p><strong>Objectives: </strong>This exploratory study, initiated before phase IIb/III studies, assessed the efficacy and safety of BKZ in patients with radiographic (r-)axSpA and its effect on new bone formation.</p><p><strong>Design: </strong>Patients were randomised 2:1 to BKZ 160 mg every 2 weeks (Q2W; Weeks 0-10) then 320 mg Q4W (Weeks 12-44), or the reference drug: certolizumab pegol (CZP) 400 mg Q2W (Weeks 0-4), then 200 mg Q2W (Weeks 6-10), 400 mg Q4W (Weeks 12-44).</p><p><strong>Methods: </strong>Primary (Axial Spondyloarthritis Disease Activity Score (ASDAS) change from baseline (CfB)) and secondary endpoints (ASDAS-ID, ASDAS-MI) were assessed at Week 12. PET-positive axSpA lesion counts and osteoblastic activity quantification (mean SUV_auc) were performed at baseline and Weeks 12 and 48 in the sacroiliac joints and spine (PET-CT substudy; not powered to evaluate differences).</p><p><strong>Results: </strong>In total, 76 patients were randomised; 26/76 entered the PET-CT substudy. At Week 12, the mean ASDAS CfB with BKZ was -2.1 (CZP: -1.8); ASDAS-ID and ASDAS-MI were achieved by 23.9% (11/46) (CZP: 20.8% (5/24)) and 60.9% (28/46) (CZP: 45.8% (11/24)) patients. Across treatments, clinical efficacy was maintained or increased further at Week 48. In the PET-CT substudy, the total number of PET-positive axSpA lesions and mean SUV_auc were substantially reduced from baseline at Week 12 with BKZ and CZP, with reductions maintained or further reduced at Week 48. Treatments were well tolerated with no new safety signals.</p><p><strong>Conclusion: </strong>Dual inhibition of IL-17A and IL-17F with BKZ resulted in improved clinical outcomes and reduced osteoblastic activity in patients with r-axSpA, suggesting the potential of BKZ to reduce disease activity and new bone formation within 12 weeks of treatment. CZP findings were consistent with previous data. No new safety signals were identified.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT03215277 (https://clinicaltrials.gov/study/NCT03215277).</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"16 ","pages":"1759720X241293944"},"PeriodicalIF":3.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thoracic manifestations of rheumatic disease: a radiologist's view.","authors":"Alexander De Clercq, Lennart Jans, Robert Gosselin, Louke Delrue, Elke Vereecke, Anagha P Parkar, Eva Schiettecatte, Clarisse Lecluyse, Peter Smeets, Nele Herregods, Lieve Morbée","doi":"10.1177/1759720X241293943","DOIUrl":"https://doi.org/10.1177/1759720X241293943","url":null,"abstract":"<p><p>With varying prevalence and manifestations depending on the underlying disease, thoracic involvement is one of the major factors determining morbidity and mortality in patients with rheumatic diseases (RDs). The most frequent pulmonary complication is interstitial lung disease (ILD), but other thoracic manifestations can also be present. Often, the only way to depict these extra-articular manifestations of disease is through imaging. Making an early diagnosis and thus aiding in the appropriate management requires radiologists to possess a comprehensive understanding of the typical imaging findings and the accompanying clinical context. In this review, the common features of thoracic involvement in RD are systematically described, with illustrations and explanatory drawings. ILD patterns, rheumatoid nodules, bronchial involvement, esophageal involvement, and pleural and pericardial disease are among the features discussed.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"16 ","pages":"1759720X241293943"},"PeriodicalIF":3.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Switching from rituximab originator to GP2013 or CT-P10 biosimilars in autoimmune rheumatic diseases: drug retention rate and safety data from a multicentric retrospective cohort.","authors":"Stefano Gentileschi, Cosimo Bruni, Carla Gaggiano, Roberto D'Alessandro, Giovanni Pacini, Jurgen Sota, Serena Guiducci, Marco Matucci Cerinic, Bruno Frediani","doi":"10.1177/1759720X241292312","DOIUrl":"10.1177/1759720X241292312","url":null,"abstract":"<p><strong>Background: </strong>Real-world evidence supporting a safe and effective transition from rituximab originator (RTX-O) to its biosimilars (RTX-B) in autoimmune rheumatic diseases (ARDs) is still limited.</p><p><strong>Objectives: </strong>The primary aims of this study were to evaluate the long-term persistence of RTX-B after the non-medical switch (NMS) from RTX-O in ARD patients, and to explore the RTX-B safety profile. The secondary aims were to evaluate the impact of different factors on RTX-B drug retention rate (DRR) and to identify any factors associated with RTX-B discontinuation.</p><p><strong>Design: </strong>Retrospective observational study.</p><p><strong>Methods: </strong>We included consecutive ARD patients undergoing NMS from RTX-O to GP2013 or CT-P10 from January 2018 to December 2020. RTX-B DRR was estimated by Kaplan-Meier plot analysis and compared according to different factors by the Log-rank test; the Cox proportional hazard model was used to detect factors associated with RTX-B discontinuation in the first 36 months.</p><p><strong>Results: </strong>We enrolled 181 patients switching to RTX-B: GP2013 in 143 (79.0%) cases and CT-P10 in 38 (21.0%). The estimated DRR for RTX-B was 81.5% at 12 months, 80.6% at 24 months, and 77.4% at 36 months. The incidence of adverse events with RTX-B was 12.6/100 patients/year. In the Log-rank test, no statistically significant differences were observed in the RTX-B DRR according to sex (<i>p</i> = 0.171), ARD diagnosis (<i>p</i> = 0.281), and concomitant immunosuppressive therapy (<i>p</i> = 0.054); on the contrary, patients on GP2013 showed a higher DRR than those on CT-P10 (<i>p</i> < 0.001). In the Cox proportional hazard analysis, the switch to CT-P10 was associated with a higher probability of stopping treatment (hazard ratio, 1.83 (confidence interval, 1.10-3.04), <i>p</i> = 0.02).</p><p><strong>Conclusion: </strong>NMS to RTX-B is associated with a high chance of retaining the drug for up to 36 months, irrespective of the diagnosis. GP2013 showed a higher retention rate than CT-P10.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"16 ","pages":"1759720X241292312"},"PeriodicalIF":3.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interplay between dysregulated metabolites and signaling pathway alterations involved in osteoarthritis: a systematic review.","authors":"Atiqah Aziz, Kavitha Ganesan Nathan, Tunku Kamarul, Ali Mobasheri, Alimohammad Sharifi","doi":"10.1177/1759720X241299535","DOIUrl":"10.1177/1759720X241299535","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a common degenerative joint disease that poses a significant global healthcare challenge due to its complexity and limited treatment options. Advances in metabolomics have provided insights into OA by identifying dysregulated metabolites and their connection to altered signaling pathways. However, a comprehensive understanding of these biomarkers in OA is still required.</p><p><strong>Objectives: </strong>This systematic review aims to identify metabolomics biomarkers associated with dysregulated signaling pathways in OA, using data from various biological samples, including in vitro models, animal studies, and human research.</p><p><strong>Design: </strong>A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.</p><p><strong>Data sources and methods: </strong>Data were gathered from literature published between August 2017 and May 2024, using databases such as \"PubMed,\" \"Scopus,\" \"Web of Science,\" and \"Google Scholar.\" Studies were selected based on keywords like \"metabolomics,\" \"osteoarthritis,\" \"amino acids,\" \"molecular markers,\" \"biomarkers,\" \"diagnostic markers,\" \"inflammatory cytokines,\" \"molecular signaling,\" and \"signal transduction.\" The review focused on identifying key metabolites and their roles in OA-related pathways. Limitations include the potential exclusion of studies due to keyword selection and strict inclusion criteria.</p><p><strong>Results: </strong>The meta-analysis identified dysregulated metabolites and associated pathways, highlighting a distinct set of related metabolites consistently altered across the studies analyzed. The dysregulated metabolites, including amino acids, lipids, and carbohydrates, were found to play critical roles in inflammation, oxidative stress, and energy metabolism in OA. Metabolites such as alanine, lysine, and proline were frequently linked to pathways involved in inflammation, cartilage degradation, and apoptosis. Key pathways, including nuclear factor kappa B, mitogen-activated protein kinase, Wnt/β-catenin, and mammalian target of rapamycin, were associated with changes in metabolite levels, particularly in proinflammatory lipids and energy-related compounds.</p><p><strong>Conclusion: </strong>This review reveals a complex interplay between dysregulated metabolites and signaling pathways in OA, offering potential biomarkers and therapeutic targets. Further research is needed to explore the molecular mechanisms driving these changes and their implications for OA treatment.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"16 ","pages":"1759720X241299535"},"PeriodicalIF":3.4,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence in rheumatology: status quo and quo vadis-results of a national survey among German rheumatologists.","authors":"Marie-Therese Holzer, Anna Meinecke, Felix Müller, Isabell Haase, Harriet Morf, Thorben Witte, Hannah Labinsky, Philipp Klemm, Johannes Knitza, Martin Krusche","doi":"10.1177/1759720X241275818","DOIUrl":"10.1177/1759720X241275818","url":null,"abstract":"<p><strong>Background: </strong>The development and potential of artificial intelligence (AI) is remarkable. Its application in all medical disciplines, including rheumatology, is attracting attention. To what extent AI is already used in clinical routine in rheumatology is unknown. In addition, the perceived barriers, potentials, and expectations regarding AI by rheumatologists have not yet been studied.</p><p><strong>Objectives: </strong>To examine the current usage and perceived barriers and facilitators of AI, including large language models (LLMs), among rheumatologists.</p><p><strong>Design: </strong>National, observational, non-interventional, and cross-sectional web-based study.</p><p><strong>Methods: </strong>A web-based survey was developed by the Working Group Young Rheumatology (AGJR) of the German Society for Rheumatology. The survey was distributed at the Congress of the German Society for Rheumatology and via social media, QR code, and email from August 30 until November 4, 2023.</p><p><strong>Results: </strong>Responses from 172 rheumatologists (55% female; mean age 43 years) were analyzed. The majority stated that they did not previously use AI (73%) in their daily practice. Eighty-eight percent of rheumatologists rated their AI knowledge as low to intermediate and 84% would welcome dedicated training on LLMs. The majority of rheumatologists anticipated AI implementation to improve patient care (60%) and reduce daily workload (62%). Especially for diagnosis (73%), writing medical reports (70%), and data analysis (70%), rheumatologists reported a potential positive benefit of AI. Main AI concerns addressed the responsibility for medical decisions (64%) and data security (58%).</p><p><strong>Conclusion: </strong>Overall, the results indicate that rheumatologists currently have little AI knowledge and make very little use of AI in clinical routine. However, the majority of rheumatologists anticipate positive AI effects and would welcome increased AI implementation and dedicated training programs.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"16 ","pages":"1759720X241275818"},"PeriodicalIF":3.4,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of achieving clinical disease control criteria and patient-reported outcomes in bimekizumab-treated patients with active psoriatic arthritis: results from two phase III studies.","authors":"Lars Erik Kristensen, William Tillett, Peter Nash, Laura C Coates, Philip J Mease, Alexis Ogdie, Paolo Gisondi, Barbara Ink, Adam R Prickett, Rajan Bajracharya, Vanessa Taieb, Nikos Lyris, Jérémy Lambert, Jessica A Walsh","doi":"10.1177/1759720X241288071","DOIUrl":"https://doi.org/10.1177/1759720X241288071","url":null,"abstract":"<p><strong>Background: </strong>Psoriatic arthritis (PsA) is a chronic inflammatory disease that causes pain and fatigue, reduces physical function, and negatively impacts health-related quality of life (HRQoL). In the phase III BE OPTIMAL and BE COMPLETE studies, bimekizumab demonstrated clinical efficacy and meaningful improvements in patient-reported outcome (PRO) measures in biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients, and those who had prior inadequate response/intolerance to tumor necrosis factor inhibitors (TNFi-IR).</p><p><strong>Objectives: </strong>To examine the association between achieving increasingly stringent clinical disease control criteria and improvements in PRO measures in patients with active PsA receiving bimekizumab.</p><p><strong>Design: </strong>Post hoc analysis of two phase III studies.</p><p><strong>Methods: </strong>BE OPTIMAL and BE COMPLETE assessed subcutaneous bimekizumab 160 mg every 4 weeks in bDMARD-naïve and TNFi-IR patients with active PsA. Disease control was assessed using American College of Rheumatology (ACR) response criteria, Minimal Disease Activity, Disease Activity Index for Psoriatic Arthritis, and the composite outcome of ACR50 and 100% improvement in Psoriasis Area and Severity Index. Associations between clinical disease control criteria and PRO measures of pain, fatigue, physical function, and HRQoL were assessed at week 16 and week 52/40 (BE OPTIMAL/BE COMPLETE).</p><p><strong>Results: </strong>Achievement of increasingly stringent clinical disease control criteria was generally associated with sequentially greater improvements in all PRO measures, including pain. At week 52/40, 94.7% of bDMARD-naïve and 97.6% of TNFi-IR patients achieving ACR70 reported ⩾50% improvements in pain from baseline, and the greatest numerical improvements (-48.5 bDMARD-naïve; -54.7 TNFi-IR). This pattern was evident as early as week 16 and sustained when assessed at week 52/40 across the majority of clinical disease control criteria and PRO measures reported.</p><p><strong>Conclusion: </strong>The achievement of increasingly stringent thresholds of disease control was associated with corresponding greater improvements in PROs, for patients receiving bimekizumab treatment, irrespective of prior TNFi use.</p><p><strong>Trial registration clinicaltrialsgov: </strong>NCT03895203, NCT03896581, and NCT04009499.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"16 ","pages":"1759720X241288071"},"PeriodicalIF":3.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors and prognosis of depression in Takayasu arteritis patients.","authors":"Yaxin Zhang, Anyuyang Fan, Juan Du, Xuemei Shi, Shiyu Yang, Na Gao, Lili Pan, Taotao Li","doi":"10.1177/1759720X241296414","DOIUrl":"https://doi.org/10.1177/1759720X241296414","url":null,"abstract":"<p><strong>Background: </strong>Takayasu arteritis (TA) is associated with an increased risk of developing complicated comorbidities, which can bring both psychological and physical burdens to the patients.</p><p><strong>Objective: </strong>TA is found to carry a high risk of developing depression. This research aimed to investigate the risk factors and prognosis of depression in TA patients.</p><p><strong>Design: </strong>A longitudinal observation cohort was conducted on TA patients with or without depression to explore the clinical characteristics.</p><p><strong>Methods: </strong>In this cohort study, 90 TA patients were split into two groups with or without depression. Depression was evaluated by the Hospital Anxiety and Depression Scale (HADS) in TA patients. TA patients with depression were followed up for at least 3 months. We used multivariate logistic regression analysis to find the risk factors and Kaplan-Meier curve analysis to determine the prognosis.</p><p><strong>Results: </strong>We concluded 90 TA patients in this research, 29 of whom were in depression. Indian Takayasu's Arteritis Activity Score (ITAS2010) ⩾2 (odds ratio (OR) (95% confidence interval, CI) 26.664 (2.004-354.741), <i>p</i> = 0.013), interleukin-6 (IL-6) (OR (95% CI) 1.070 (1.022-1.121), <i>p</i> = 0.004), prednisone equivalents (OR (95% CI) 1.101 (1.030-1.177), <i>p</i> = 0.005), and carotidynia (OR (95% CI) 5.829 (1.142-29.751), <i>p</i> = 0.034) have been shown independent risk factors for depression in TA patients. We also identified the association between disease remission with the improvement of HADS-D score (Log-rank <i>p</i> = 0.005, hazard ratio (HR) 0.25) and depression (Log-rank <i>p</i> = 0.043, HR 0.28).</p><p><strong>Conclusion: </strong>Aggressive treatment to achieve remission can promote improvement of depression in patients with TA. Screening for depression should also be performed in patients with elevated disease activity, IL-6, glucocorticoid use, and carotidynia.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"16 ","pages":"1759720X241296414"},"PeriodicalIF":3.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation of changes in inflammatory and collagen biomarkers with durable guselkumab efficacy through 2 years in participants with active psoriatic arthritis: results from a phase III randomized controlled trial.","authors":"Stefan Siebert, Georg Schett, Siba P Raychaudhuri, Monica Guma, Warner Chen, Sheng Gao, Soumya D Chakravarty, Frederic Lavie, Proton Rahman","doi":"10.1177/1759720X241283536","DOIUrl":"10.1177/1759720X241283536","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Guselkumab (human monoclonal antibody) selectively inhibits the interleukin (IL)-23p19 subunit.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;Assess the longer-term pharmacodynamic effects of guselkumab and explore associations between such effects and clinical responses in patients with active psoriatic arthritis (PsA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;DISCOVER-2 randomized 739 biologic-naïve patients with active PsA (swollen/tender joint counts each ⩾5, C-reactive protein (CRP) ⩾0.6 mg/dL) to guselkumab (100 mg every 4 weeks (Q4W) or at Weeks 0, 4, and then Q8W) or placebo. Guselkumab-randomized participants with available serum biomarker data (randomly selected to reflect demographic and disease characteristics of the DISCOVER-2 population) comprised inflammatory (&lt;i&gt;N&lt;/i&gt; = 100) and collagen (&lt;i&gt;N&lt;/i&gt; = 178) biomarker cohorts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Pharmacodynamic effects of guselkumab through 2 years on inflammatory and collagen biomarker levels (general linear model) and associations between biomarkers and improvements in composite measures of joint, skin, and overall disease activity (Spearman linear regression) through 2 years were assessed. The relationship between the pharmacodynamic effects of guselkumab and achieving ⩾50% improvement in the American College of Rheumatology response criteria (ACR50) was assessed using a general linear model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;With guselkumab, pharmacodynamic effects on inflammatory (CRP, IL-6, serum amyloid A (SAA), IL-17A, IL-17F, IL-22, and beta-defensin 2 (BD-2)) and collagen (matrix metalloproteinase-degradation type I, III, IV, and VI collagen (C1M, C3M, C4M, and C6M)) biomarker levels were sustained or enhanced through Week 100. Throughout follow-up timepoints (Week 24/52/100), decreases in CRP, IL-6, C1M, and C6M levels correlated (&lt;i&gt;r&lt;/i&gt; = 0.26-0.30; &lt;i&gt;p&lt;/i&gt; &lt; 0.05) with improved joint disease activity (Disease Activity in Psoriatic Arthritis); decreases in IL-17A, IL-17F, IL-22, and BD-2 levels correlated (&lt;i&gt;r&lt;/i&gt; = 0.34-0.58; &lt;i&gt;p&lt;/i&gt; &lt; 0.05) with improved skin disease (Psoriasis Area and Severity Index); and decreases in C1M, C3M, C4M, and C6M correlated (&lt;i&gt;r&lt;/i&gt; = 0.27-0.31; &lt;i&gt;p&lt;/i&gt; &lt; 0.05) with improved overall disease activity (Psoriatic Arthritis Disease Activity Score). Significantly (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) greater reductions from baseline at Week 100 in CRP, IL-6, SAA, and C1M levels were observed in participants improving from Week 24 ACR50 nonresponse to Week 100 ACR50 response and were accompanied by a significant decrease in C1M from Week 24 to Week 100 versus nonresponders at both Weeks 24 and 100.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In biologic-naïve participants with active PsA, guselkumab elicited substantial and enduring reductions in biomarkers that were associated with durable improvements in joint, skin, and overall disease activity through 2 years of DISCOVER-2.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/strong&gt;NCT03158285 (clinicaltrials","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"16 ","pages":"1759720X241283536"},"PeriodicalIF":3.4,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What have we learnt from the inhibition of IL-6 in RA and what are the clinical opportunities for patient outcomes?","authors":"Peter C Taylor, Eugen Feist, Janet E Pope, Peter Nash, Jean Sibilia, Roberto Caporali, Alejandro Balsa","doi":"10.1177/1759720X241283340","DOIUrl":"https://doi.org/10.1177/1759720X241283340","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is an autoimmune disease characterised by persistent inflammation of the synovial joints as well as other tissues and organs. Left untreated, it can lead to joint damage, disability and even increased mortality. The disease is driven by inflammatory cytokines that contribute to the chronic inflammation seen in RA. Interleukin-6 (IL-6) is a key pathological cytokine and a target for treatments aiming to alleviate local and systemic inflammation. Despite advances in understanding RA and the introduction of new treatments, achieving sustained remission remains challenging. This review explores the role of IL-6 in RA pathogenesis, its potential as a treatment target and the significance of personalised medicine in RA management. IL-6 has a dual signalling mechanism, classical and trans-signalling, which influences various intracellular pathways. While several targeted therapies have emerged, no single mechanism-based therapy is universally effective due to the diversity and complexity of the disease. Different approaches to targeting IL-6 have been tested, including biologic blockade of receptors or ligands, and inhibition of IL-6 signalling. IL-6 receptor inhibitors have been validated as RA therapeutics, either alone or in combination with other treatments. Tocilizumab, the first approved IL-6 inhibitor, blocks both soluble and membrane-bound IL-6 receptors, reducing the inflammatory cascade. Clinical trials confirm the efficacy and safety of tocilizumab and its role as a treatment option for patients unresponsive to conventional therapies. The benefits of IL-6 inhibition extend beyond reduced joint inflammation to the amelioration of comorbidities like anaemia, cardiovascular disease, depression and osteoporosis. Tailoring treatment to patients' profiles and comorbidities is essential for optimal outcomes. A 'treat-to-profile' approach, focusing on a holistic view of the patient, could improve personalised medicine strategies. Biosimilars - lower-cost alternatives to biologics - further enhance the accessibility and cost-effectiveness of treatment. IL-6 inhibitors present a valuable treatment option for RA management, particularly for patients with specific comorbidities.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"16 ","pages":"1759720X241283340"},"PeriodicalIF":3.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging in psoriatic arthritis: established methods and emerging techniques.","authors":"Yingzhao Jin, Isaac T Cheng, Dongze Wu, Xianfeng Yan, Sze-Lok Lau, Nga Sze Wong, Vivian W Hung, Ling Qin, Ryan Ka Lok Lee, James F Griffith, Cheuk-Chun Szeto, Ho So, Lai-Shan Tam","doi":"10.1177/1759720X241288060","DOIUrl":"https://doi.org/10.1177/1759720X241288060","url":null,"abstract":"<p><p>Psoriatic arthritis (PsA) is a heterogeneous, chronic, inflammatory musculoskeletal disease that can lead to peripheral and axial damage and loss of function. A clear difference between PsA and other forms of inflammatory arthritis is the different forms of bone remodeling seen in PSA which incorporates not only increased bone resorption with bone erosions, osteolysis, and loss of bone mineral density but also increased bone formation with periostitis, syndesmophytes, enthesiophytes, and ankylosis. PsA, if diagnosed late, will lead to significant structural damage, the most severe form of which is known as arthritis mutilans, and loss of physical function. Imaging plays a crucial role in diagnosing and monitoring both peripheral and axial conditions associated with PsA. Radiography is currently the main modality used to monitor structural damage in PsA though commonly used scoring systems do not include bony proliferation as a criterion. Besides, radiography is limited in determining the presence and cause of periarticular soft tissue thickening, which may arise from tendinosis, tenosynovitis, synovial proliferation, bursitis, or enthesitis. Recently, much more attention has been paid to determining the imaging characteristics of PsA, which enables more precise identification of disease and severity assessment. Newer imaging technologies also enable variations in normal bone microstructure to be distinguished from disease-related abnormality. This review discusses the current state of innovative imaging modalities in PsA, specifically concentrating on their roles in PsA diagnosis and treatment, improving the early detection of PsA, and identifying patients with skin psoriasis at risk of developing psoriatic arthritis.</p>","PeriodicalId":23056,"journal":{"name":"Therapeutic Advances in Musculoskeletal Disease","volume":"16 ","pages":"1759720X241288060"},"PeriodicalIF":3.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}