Annals of the Rheumatic Diseases最新文献

{"title":"EULAR recommendations for the involvement of patient research partners in rheumatology research: 2023 update.","authors":"Maarten de Wit, Krystel Aouad, Muriel Elhai, Diego Benavent, Heidi Bertheussen, Steven Blackburn, Peter Böhm, Catia Duarte, Marie Falahee, Susanne Karlfeldt, Uta Kiltz, Elsa F Mateus, Dawn P Richards, Javier Rodríguez-Carrio, Joachim Sagen, Russka Shumnalieva, Simon R Stones, Sander W Tas, William Tillett, Ana Vieira, Tanita-Christina Wilhelmer, Condruta Zabalan, Jette Primdahl, Paul Studenic, Laure Gossec","doi":"10.1136/ard-2024-225566","DOIUrl":"10.1136/ard-2024-225566","url":null,"abstract":"<p><strong>Background: </strong>Since the publication of the 2011 European Alliance of Associations for Rheumatology (EULAR) recommendations for patient research partner (PRP) involvement in rheumatology research, the role of PRPs has evolved considerably. Therefore, an update of the 2011 recommendations was deemed necessary.</p><p><strong>Methods: </strong>In accordance with the EULAR Standardised Operational Procedures, a task force comprising 13 researchers, 2 health professionals and 10 PRPs was convened. The process included an online task force meeting, a systematic literature review and an in-person second task force meeting to formulate overarching principles (OAPs) and recommendations. The level of agreement of task force members was assessed anonymously (0-10 scale).</p><p><strong>Results: </strong>The task force developed five new OAPs, updated seven existing recommendations and formulated three new recommendations. The OAPs address the definition of a PRP, the contribution of PRPs, the role of informal caregivers, the added value of PRPs and the importance of trust and communication in collaborative research efforts. The recommendations address the research type and phases of PRP involvement, the recommended number of PRPs per project, the support necessary for PRPs, training of PRPs and acknowledgement of PRP contributions. New recommendations concern the benefits of support and guidance for researchers, the need for regular evaluation of the patient-researcher collaboration and the role of a designated coordinator to facilitate collaboration. Agreements within the task force were high and ranged between 9.16 and 9.96.</p><p><strong>Conclusion: </strong>The updated EULAR recommendations for PRP involvement are more substantially based on evidence. Together with added OAPs, they should serve as a guide for researchers and PRPs and will ultimately strengthen the involvement of PRPs in rheumatology research.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1443-1453"},"PeriodicalIF":20.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defects in B-lymphopoiesis and B-cell maturation underlie prolonged B-cell depletion in ANCA-associated vasculitis.","authors":"Jens Thiel, Franziska M Schmidt, Raquel Lorenzetti, Arianna Troilo, Iga Janowska, Lena Nießen, Sophie Pfeiffer, Julian Staniek, Bruno Benassini, Marei-Theresa Bott, Jakov Korzhenevich, Lukas Konstantinidis, Frank Burgbacher, Ann-Katrin Dufner, Natalie Frede, Reinhard E Voll, Jan Stuchly, Marina Bakardjieva, Tomas Kalina, Cristian Roberto Smulski, Nils Venhoff, Marta Rizzi","doi":"10.1136/ard-2024-225587","DOIUrl":"10.1136/ard-2024-225587","url":null,"abstract":"<p><strong>Objectives: </strong>B-cell depletion time after rituximab (RTX) treatment is prolonged in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with other autoimmune diseases. We investigated central and peripheral B-cell development to identify the causes for the defect in B-cell reconstitution after RTX therapy.</p><p><strong>Methods: </strong>We recruited 91 patients with AAV and performed deep phenotyping of the peripheral and bone marrow B-cell compartment by spectral flow and mass cytometry. B-cell development was studied by <i>in vitro</i> modelling and the role of BAFF receptor by quantitative PCR, western blot analysis and <i>in vitro</i> assays.</p><p><strong>Results: </strong>Treatment-naïve patients with AAV showed low transitional B-cell numbers, suggesting impaired B-lymphopoiesis. We analysed bone marrow of treatment-naïve and RTX-treated patients with AAV and found reduced B-lymphoid precursors. <i>In vitro</i> modelling of B-lymphopoiesis from AAV haematopoietic stem cells showed intact, but slower and reduced immature B-cell development. In a subgroup of patients, after RTX treatment, the presence of transitional B cells did not translate in replenishment of naïve B cells, suggesting an impairment in peripheral B-cell maturation. We found low BAFF-receptor expression on B cells of RTX-treated patients with AAV, resulting in reduced survival in response to BAFF <i>in vitro</i>.</p><p><strong>Conclusions: </strong>Prolonged depletion of B cells in patients with AAV after RTX therapy indicates a B-cell defect that is unmasked by RTX treatment. Our data indicate that impaired bone marrow B-lymphopoiesis results in a delayed recovery of peripheral B cells that may be further aggravated by a survival defect of B cells. Our findings contribute to the understanding of AAV pathogenesis and may have clinical implications regarding RTX retreatment schedules and immunomonitoring after RTX therapy.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1536-1548"},"PeriodicalIF":20.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Ensuring tight control in patients with rheumatoid arthritis treated with targeted therapies during the COVID-19 pandemic using a telehealth strategy.","authors":"","doi":"10.1136/ard-2021-220142corr1","DOIUrl":"10.1136/ard-2021-220142corr1","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":"83 11","pages":"e27"},"PeriodicalIF":20.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of sequential therapy with subcutaneous belimumab and one cycle of rituximab in patients with systemic lupus erythematosus: the phase 3, randomised, placebo-controlled BLISS-BELIEVE study.","authors":"Cynthia Aranow, Cornelia F Allaart, Zahir Amoura, Ian N Bruce, Patricia C Cagnoli, Walter W Chatham, Kenneth L Clark, Richard Furie, James Groark, Murray B Urowitz, Ronald van Vollenhoven, Mark Daniels, Norma Lynn Fox, Yun Irene Gregan, Robert B Henderson, André van Maurik, Josephine C Ocran-Appiah, Mary Oldham, David A Roth, Don Shanahan, Paul P Tak, Yk Onno Teng","doi":"10.1136/ard-2024-225686","DOIUrl":"10.1136/ard-2024-225686","url":null,"abstract":"<p><strong>Objectives: </strong>Disease activity control in patients with systemic lupus erythematosus (SLE) with corticosteroid and immunosuppressant withdrawal is a treatment goal. We evaluated whether this could be attained with sequential subcutaneous belimumab (BEL) and one cycle of rituximab (RTX).</p><p><strong>Methods: </strong>In this phase 3, double-blind BLISS-BELIEVE trial (GSK Study 205646), patients with active SLE initiating subcutaneous BEL 200 mg/week for 52 weeks were randomised to intravenous placebo (BEL/PBO) or intravenous RTX 1000 mg (BEL/RTX) at weeks 4 and 6 while stopping concomitant immunosuppressants/tapering corticosteroids; standard therapy for 104 weeks (BEL/ST; reference arm) was included.</p><p><strong>Primary endpoint: </strong>proportion of patients achieving disease control (SLE Disease Activity Index-2000 (SLEDAI-2K) ≤2; without immunosuppressants; prednisone equivalent ≤5 mg/day) at week 52 with BEL/RTX versus BEL/PBO. Major (alpha-controlled) secondary endpoints: proportion of patients with clinical remission (week 64; clinical SLEDAI-2K=0, without immunosuppressants/corticosteroids); proportion of patients with disease control (week 104). Other assessments: disease control duration, anti-dsDNA antibody, C3/C4 and B cells/B-cell subsets.</p><p><strong>Results: </strong>The modified intention-to-treat population included 263 patients. Overall, 16.7% (12/72) of BEL/PBO and 19.4% (28/144) of BEL/RTX patients achieved disease control (OR (95% CI) 1.27 (0.60 to 2.71); p=0.5342) at week 52. For major secondary endpoints, differences between BEL/RTX and BEL/PBO were not statistically significant. Anti-dsDNA antibodies and most assessed B cells/B-cell subsets were lower with BEL/RTX versus BEL/PBO. Mean disease control duration through 52 weeks was significantly greater with BEL/RTX versus BEL/PBO.</p><p><strong>Conclusions: </strong>BEL/RTX showed no superiority over BEL/PBO for most endpoints analysed; however, it led to significant improvements in disease activity markers compared with BEL/PBO. Further investigation of combination treatment is warranted.</p><p><strong>Trial registration number: </strong>NCT03312907.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1502-1512"},"PeriodicalIF":20.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to: Correspondence on 'Current myositis clinical trials and tribulations' by Saygin <i>et al</i>.","authors":"Didem Saygin, Victoria Werth, Julie J Paik, Jin Kyun Park, Merrilee Needham, Ingrid E Lundberg, Lisa Christopher-Stine","doi":"10.1136/ard-2024-225762","DOIUrl":"10.1136/ard-2024-225762","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"e23"},"PeriodicalIF":20.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors associated with disease flare following SARS-CoV-2 vaccination in people with inflammatory rheumatic and musculoskeletal diseases: results from the physician-reported EULAR Coronavirus Vaccine (COVAX) Registry.","authors":"Bayram Farisogullari, Saskia Lawson-Tovey, Kimme L Hyrich, Laure Gossec, Loreto Carmona, Anja Strangfeld, Elsa F Mateus, Martin Schäfer, Ana Rodrigues, Eric Hachulla, Jose A Gomez-Puerta, Marta Mosca, Patrick Durez, Ludovic Trefond, Tiphaine Goulenok, Martina Cornalba, Emoke Stenova, Inita Bulina, Eva Strakova, Julija Zepa, Nicolas Roux, Olivier Brocq, Eric Veillard, Bernd Raffeiner, Gerd R Burmester, Xavier Mariette, Pedro M Machado","doi":"10.1136/ard-2024-225869","DOIUrl":"10.1136/ard-2024-225869","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs).</p><p><strong>Methods: </strong>Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors.</p><p><strong>Results: </strong>The study included 7336 patients with I-RMD, with 272 of 7336 (3.7%) experiencing flares and 121 of 7336 (1.6%) experiencing flares requiring starting a new medication or increasing the dosage of an existing medication. Factors independently associated with increased odds of flare were: female sex (OR=1.40, 95% CI=1.05 to 1.87), active disease at the time of vaccination (low disease activity (LDA), OR=1.45, 95% CI=1.08 to 1.94; moderate/high disease activity (M/HDA), OR=1.37, 95% CI=0.97 to 1.95; vs remission), and cessation/reduction of antirheumatic medication before or after vaccination (OR=4.76, 95% CI=3.44 to 6.58); factors associated with decreased odds of flare were: higher age (OR=0.90, 95% CI=0.83 to 0.98), non-Pfizer/AstraZeneca/Moderna vaccines (OR=0.10, 95% CI=0.01 to 0.74; vs Pfizer), and exposure to methotrexate (OR=0.57, 95% CI=0.37 to 0.90), tumour necrosis factor inhibitors (OR=0.55, 95% CI=0.36 to 0.85) or rituximab (OR=0.27, 95% CI=0.11 to 0.66), versus no antirheumatic treatment. In a multivariable model using new medication or dosage increase due to flare as the dependent variable, only the following independent associations were observed: active disease (LDA, OR=1.47, 95% CI=0.94 to 2.29; M/HDA, OR=3.08, 95% CI=1.91 to 4.97; vs remission), cessation/reduction of antirheumatic medication before or after vaccination (OR=2.24, 95% CI=1.33 to 3.78), and exposure to methotrexate (OR=0.48, 95% CI=0.26 to 0.89) or rituximab (OR=0.10, 95% CI=0.01 to 0.77), versus no antirheumatic treatment.</p><p><strong>Conclusion: </strong>I-RMD flares following SARS-CoV-2 vaccination were uncommon. Factors associated with flares were identified, namely higher disease activity and cessation/reduction of antirheumatic medications before or after vaccination.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1584-1595"},"PeriodicalIF":20.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of tofacitinib for the treatment of patients with juvenile idiopathic arthritis: preliminary results of an open-label, long-term extension study.","authors":"Hermine I Brunner, Jonathan D Akikusa, Eslam Al-Abadi, John F Bohnsack, Alina Lucica Boteanu, Gaelle Chedeville, Ruben Cuttica, Wendy De La Pena, Lawrence Jung, Ozgur Kasapcopur, Katarzyna Kobusinska, Grant S Schulert, Claudia Neiva, Rafael Rivas-Chacon, Juan Cruz Rizo Rodriguez, Monica Vazquez-Del Mercado, Linda Wagner-Weiner, Jennifer E Weiss, Carine Wouters, Holly Posner, Ann Wouters, Cheng Chang, Claire White, Keith Kanik, Shixue Liu, Alberto Martini, Daniel J Lovell, Nicolino Ruperto","doi":"10.1136/ard-2023-225094","DOIUrl":"10.1136/ard-2023-225094","url":null,"abstract":"<p><strong>Objectives: </strong>We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study.</p><p><strong>Methods: </strong>Patients (2-<18 years) with JIA who completed phase 1/3 index studies or discontinued for reasons excluding treatment-related serious adverse events (AEs) entered the LTE study and received tofacitinib 5 mg two times per day or equivalent weight-based doses. Safety outcomes included AEs, serious AEs and AEs of special interest. Efficacy outcomes included improvement since tofacitinib initiation per the JIA-American College of Rheumatology (ACR)70/90 criteria, JIA flare rate and disease activity measured by Juvenile Arthritis Disease Activity Score (JADAS)27, with inactive disease corresponding to JADAS ≤1.0.</p><p><strong>Results: </strong>Of 225 patients with JIA (median (range) duration of treatment, 41.6 (1-103) months), 201 (89.3%) had AEs; 34 (15.1%) had serious AEs. 10 patients developed serious infections; three had herpes zoster. Two patients newly developed uveitis. Among patients with polyarticular course JIA, JIA-ACR70/90 response rates were 60.0% (78 of 130) and 33.6% (47 of 140), respectively, at month 1, and generally improved over time. JIA flare events generally occurred in <5% of patients through to month 48. Observed mean (SE) JADAS27 was 22.0 (0.6) at baseline, 6.2 (0.7) at month 1 and 2.8 (0.5) at month 48, with inactive disease in 28.8% (36 of 125) of patients at month 1 and 46.8% (29 of 82) at month 48.</p><p><strong>Conclusions: </strong>In this interim analysis of LTE study data in patients with JIA, safety findings were consistent with the known profile of tofacitinib, and efficacy was maintained up to month 48.</p><p><strong>Trial registration number: </strong>NCT01500551.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1561-1571"},"PeriodicalIF":20.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered CD8⁺ T cell subpopulation in the bone marrow microenvironment of cynomolgus monkeys with spontaneous ankylosing spondylitis.","authors":"Tangming Guan, Zhenhua Bian, Hongbin Gao, Yi He, Junru Yuan, Hongping Wan, Shuangjie Tang, Yongfeng Li, Jianming Qiu, Panyue Luo, Xiaolan Ye, Shi Liang, Siyu Chen, Nvlue Cai, Yezhi Guan, Jianxin Liu, Zhibin Zhao, Huanhuan Jia, Wei Yang, Wende Li","doi":"10.1136/ard-2024-226018","DOIUrl":"10.1136/ard-2024-226018","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1600-1602"},"PeriodicalIF":20.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Itaconate is a metabolic regulator of bone formation in homeostasis and arthritis.","authors":"Markus Kieler, Leona Sophia Prammer, Gerwin Heller, Melanie Hofmann, Simon Sperger, Dominik Hanetseder, Birgit Niederreiter, Andrea Komljenovic, Kristaps Klavins, Thomas Köcher, Julia Stefanie Brunner, Irena Stanic, Laura Oberbichler, Ana Korosec, Andrea Vogel, Martina Kerndl, Dominika Hromadová, Laszlo Musiejovsky, Alexander Hajto, Anja Dobrijevic, Tina Piwonka, Arvand Haschemi, Anne Miller, Philippe Georgel, Darja Marolt Presen, Johannes Grillari, Silvia Hayer, Jean-Philippe Auger, Gerhard Krönke, Omar Sharif, Daniel Aletaha, Gernot Schabbauer, Stephan Blüml","doi":"10.1136/ard-2023-224898","DOIUrl":"10.1136/ard-2023-224898","url":null,"abstract":"<p><strong>Objectives: </strong>Bone remodelling is a highly dynamic process dependent on the precise coordination of osteoblasts and haematopoietic-cell derived osteoclasts. Changes in core metabolic pathways during osteoclastogenesis, however, are largely unexplored and it is unknown whether and how these processes are involved in bone homeostasis.</p><p><strong>Methods: </strong>We metabolically and transcriptionally profiled cells during osteoclast and osteoblast generation. Individual gene expression was characterised by quantitative PCR and western blot. Osteoblast function was assessed by Alizarin red staining. immunoresponsive gene 1 (<i>Irg1</i>)<i>-</i>deficient mice were used in various inflammatory or non-inflammatory models of bone loss. Tissue gene expression was analysed by RNA in situ hybridisation.</p><p><strong>Results: </strong>We show that during differentiation preosteoclasts rearrange their tricarboxylic acid cycle, a process crucially depending on both glucose and glutamine. This rearrangement is characterised by the induction of <i>Irg1</i> and production of itaconate, which accumulates intracellularly and extracellularly. While the IRG1-itaconate axis is dispensable for osteoclast generation in vitro and in vivo, we demonstrate that itaconate stimulates osteoblasts by accelerating osteogenic differentiation in both human and murine cells. This enhanced osteogenic differentiation is accompanied by reduced proliferation and altered metabolism. Additionally, supplementation of itaconate increases bone formation by boosting osteoblast activity in mice. Conversely, <i>Irg1-</i>deficient mice exhibit decreased bone mass and have reduced osteoproliferative lesions in experimental arthritis.</p><p><strong>Conclusion: </strong>In summary, we identify itaconate, generated as a result of the metabolic rewiring during osteoclast differentiation, as a previously unrecognised regulator of osteoblasts.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1465-1479"},"PeriodicalIF":20.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy, safety and tolerability of GSK3858279, an anti-CCL17 monoclonal antibody and analgesic, in healthy volunteers and patients with knee osteoarthritis pain: a phase I, randomised, double-blind, placebo-controlled, proof-of-mechanism and proof-of-concept study.","authors":"Jagtar Singh Nijjar, Katharine Abbott-Banner, Yolanda Alvarez, Nicola Aston, Damon Bass, Jane H Bentley, Joanne Ellis, Christian Ellson, Edward C Emery, Maria Feeney, Disala Fernando, David Inman, Rejbinder Kaur, Louise K Modis, Sam Munoz Vicente, Catherine Muya, Kiran Nistala, Eirini Panoilia, Riju Ray, Sarah Siederer, Julia E Smith, Lucinda Weir, Nicolas Wisniacki","doi":"10.1136/ard-2023-225434","DOIUrl":"10.1136/ard-2023-225434","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this study was to evaluate efficacy, safety and tolerability of the first-in-class, anti-CCL17 monoclonal antibody, GSK3858279, in treating knee osteoarthritis (OA) pain.</p><p><strong>Methods: </strong>This was a phase I, randomised, placebo-controlled, two-part, proof-of-mechanism and proof-of-concept study. In part A, healthy participants were randomised 3:1 to receive GSK3858279 as either single intravenous (0.1-10 mg/kg) doses, a subcutaneous (3 mg/kg up to 240 mg maximum) dose, or placebo, to evaluate safety and tolerability. In part B, participants with knee OA pain were randomised 1:1 to receive weekly subcutaneous 240 mg GSK3858279, or placebo, for 8 weeks, to assess safety and change from baseline (CFB) in average and worst knee pain intensity. Exploratory endpoints included CFB in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function and stiffness scores.</p><p><strong>Results: </strong>GSK3858279 demonstrated greater median CFB (95% credible interval (CrI)) in average and worst knee pain intensity versus placebo (average, -1.18 (-2.15, -0.20); worst, -1.09 (-2.29, 0.12)) at week 8. Median CFB (95% CrI) for GSK3858279 versus placebo in WOMAC pain and function scores were -1.41 (-2.35, -0.46) and -1.29 (-2.28, -0.29), respectively, at week 8. Overall, 72% (26/36; part A) and 88% (21/24; part B) of participants receiving GSK3858279 experienced adverse events (AEs); with nasopharyngitis being the most common in part A and injection site reactions in part B. No serious AEs or deaths were observed.GSK3858279 improved pain intensity and WOMAC pain and function scores in adults with knee OA pain and demonstrated favourable safety and tolerability in both healthy participants and adults with knee OA pain.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}