Rheumatology and Therapy最新文献

{"title":"Clinical and Ultrasonographic Remission in Bio-naïve and Bio-failure Patients with Rheumatoid Arthritis at 24 Weeks of Upadacitinib Treatment: The UPARAREMUS Real-Life Study.","authors":"Andrea Picchianti Diamanti, Maria Sofia Cattaruzza, Simonetta Salemi, Roberta Di Rosa, Giorgio Sesti, Chiara De Lorenzo, Gloria Maria Felice, Bruno Frediani, Caterina Baldi, Maria Sole Chimenti, Arianna D'Antonio, Gloria Crepaldi, Michele Maria Luchetti, Valentino Paci, Alen Zabotti, Ivan Giovannini, Marco Canzoni, Giandomenico Sebastiani, Chiara Scirocco, Carlo Perricone, Bruno Laganà, Annamaria Iagnocco","doi":"10.1007/s40744-024-00712-y","DOIUrl":"10.1007/s40744-024-00712-y","url":null,"abstract":"<p><strong>Introduction: </strong>Clinical remission is the main target in the management of patients with rheumatoid arthritis (RA). However, several authors found synovitis in patients with RA in clinical remission at ultrasonography (US). Upadacitinib is a selective Janus kinase 1 inhibitor that achieved significantly higher remission rates than adalimumab and abatacept in patients with RA. Here we present the 24-week data of the UPAdacitinib Rheumatoid Arthritis REmission UltraSonography (UPARAREMUS) study.</p><p><strong>Methods: </strong>This is a longitudinal multicenter observational study, enrolling bio-naïve and bio-inadequate responder patients affected by RA. The primary endpoint was the proportion of patients achieving both clinical and US remission at week 24. The proportion of patients achieving clinical remission with different composite indexes at week 12 and 24 was also evaluated. US of four target joints (wrists and second metacarpophalangeal bilaterally) was performed at baseline and weeks 12/24, and US remission was defined as the absence of power Doppler (PD) signal ≥ 2 in one target joint, or PD ≥ 1 in two target joints.</p><p><strong>Results: </strong>After 12 weeks and 24 weeks, 40% and 63.6% of patients achieved US plus clinical remission. The following parameters were associated with US plus clinical remission: being bio-naïve and having a shorter disease duration, although at multivariate analysis significant odds ratio (OR) was found only for being bio-naïve.</p><p><strong>Conclusions: </strong>UPARAREMUS is the first study evaluating the efficacy of upadacitinib in reaching both clinical and US remission in patients with RA. At 24 weeks, 63.6% of patients reached the primary endpoint, the only baseline associated parameter was being bio-naïve.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"1347-1361"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender Differences in Perceptions of Psoriatic Arthritis Disease Impact, Management, and Physician Interactions: Results from a Global Patient Survey.","authors":"Lihi Eder, Pascal Richette, Laura C Coates, Valderilio F Azevedo, Joseph C Cappelleri, Edward P Johnson, Megan Hoang, Jade Moser, Meriem Kessouri","doi":"10.1007/s40744-024-00678-x","DOIUrl":"10.1007/s40744-024-00678-x","url":null,"abstract":"<p><strong>Introduction: </strong>We evaluated the impact of gender on disease severity, health-related quality of life (HRQoL), treatment management, and patient-healthcare professional (HCP) interactions from the perspectives of patients with psoriatic arthritis (PsA).</p><p><strong>Methods: </strong>Data were collected from a global online patient survey conducted by The Harris Poll (November 2, 2017 to March 12, 2018). Eligible patients were aged ≥ 18 years, with a self-reported diagnosis of PsA for > 1 year, had visited a rheumatologist/dermatologist in the past 12 months, and had reported previously using ≥ 1 conventional synthetic or biologic disease-modifying antirheumatic drug. Data were stratified by gender and analyzed descriptively, inferentially by binomial (chi-square) tests, and by multivariate logistic regression models.</p><p><strong>Results: </strong>Data from 1286 patients who participated were included: 52% were female, 48% were male. Varying perceptions of disease severity between males and females were indicated by differences in symptoms leading to a diagnosis of PsA, and in symptoms reported despite treatment; more females than males reported joint tenderness, skin patches/plaques, and enthesitis. More females than males reported a major/moderate impact of PsA on their physical activity and emotional/mental well-being. Reasons for switching medication differed between genders, with more females switching because they perceived their medication to not be effective enough related to their joint symptoms. More females than males were very satisfied with their communication with their rheumatologist and were more likely to discuss the impact of PsA on their daily lives, their treatment satisfaction, and treatment goals with their rheumatologist.</p><p><strong>Conclusions: </strong>Patients' perceptions of the impact of PsA on HRQoL, treatment management, and interactions with HCPs varied between males and females. More females than males reported major/moderate physical and emotional impacts of PsA. When treating patients, it is important for HCPs to consider the potential impact of gender on patients' experience of PsA and its symptoms. Graphical plain language summary available for this article.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"1115-1134"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Challenge of IBD-Related Arthritis Screening Questionnaires in Early and Predominantly Entheseal Phenotypes.","authors":"Alen Zabotti, Nicola Cabas, Sofia Cacioppo, Caterina Zoratti, Ivan Giovannini, Debora Berretti, Michele Maria Luchetti, Salvatore De Vita, Luca Quartuccio, Giovanni Terrosu, Marco Marino","doi":"10.1007/s40744-024-00709-7","DOIUrl":"10.1007/s40744-024-00709-7","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammatory bowel disease (IBD)-related arthritis is recognized as the most prevalent extraintestinal manifestation (EIM) of IBD. The objective of this study was to determine the prevalence and characteristics of undiagnosed IBD-related arthritis and to compare two screening questionnaires, DETection of Arthritis in Inflammatory boweL diseases (DETAIL) and IBd Identification of Spondyloarthritis Questionnaire (IBIS-q), for early disease detection.</p><p><strong>Methods: </strong>Between April and October 2023, both the DETAIL and IBIS-q questionnaires were administered to consecutive IBD outpatients visiting the University Hospital of Udine, Italy. During routine gastroenterology evaluations, patients aged > 18 years with Crohn's disease (CD) or ulcerative colitis (UC) were requested to complete both questionnaires. Subsequently, all patients who completed the questionnaires underwent a blinded rheumatological evaluation within 2 weeks. Patients with a previous diagnosis of IBD-related SpA were then excluded.</p><p><strong>Results: </strong>Overall, 203 patients were enrolled, of whom 26 were excluded because of a prior diagnosis of inflammatory arthritis. Among the remaining 177 patients, 10/177 (5.6%) received a new diagnosis of IBD-related arthritis. The median duration of symptoms before diagnosis was 4 (IQR 1.8-10.5) months. Imaging-confirmed enthesitis was the predominant pattern in 8 out 10 cases (80%, with 8 out 8 lacking concomitant peripheral arthritis), axial involvement in 1 out 10 cases (10%), and peripheral arthritis in 1 out 10 cases (10%). The DETAIL questionnaire exhibited higher specificity, but lower sensitivity compared to the IBIS-q, with a sensitivity of 40.0% (12.2-73.8) and specificity of 84.4% (78.0-89.6) versus a sensitivity of 70.0% (34.8-93.3) and specificity of 74.3% (66.9-80.7). Both questionnaires performed less effectively than in other studies.</p><p><strong>Conclusion: </strong>This study highlights a significant proportion of undiagnosed IBD-related arthritis (5.6%). Enthesitis emerged as the predominant pattern of newly diagnosed arthritis in our cohort, likely due to the recent onset of symptoms. Our study underscores the importance of entheseal involvement in early IBD-related arthritis and the importance of incorporating entheseal involvement into screening questionnaires.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"1321-1331"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ixekizumab Treatment Patterns and Health Care Resource Utilization Among Patients with Axial Spondyloarthritis: A Retrospective United States Claims Database Study.","authors":"Abhijeet Danve, Aisha Vadhariya, Jeffrey Lisse, Arjun Cholayil, Neha Bansal, Natalia Bello, Catherine Bakewell","doi":"10.1007/s40744-024-00710-0","DOIUrl":"10.1007/s40744-024-00710-0","url":null,"abstract":"<p><strong>Introduction: </strong>Real-world data on ixekizumab utilization in axial spondyloarthritis (axSpA) are limited. We evaluated ixekizumab treatment patterns and health care resource utilization (HCRU) in patients with axSpA using United States Merative L.P. MarketScan^® Claims Databases.</p><p><strong>Methods: </strong>This retrospective cohort study included adults with axSpA who initiated ixekizumab during the index period (September 2019-December 2021). Index date was the date of the first ixekizumab claim. All patients had continuous medical and pharmacy enrollment during the 12-month pre-index and follow-up periods. Descriptive statistics were used to assess patient demographics (index date); clinical characteristics (pre-index period); treatment patterns (12-month follow-up period); and HCRU (pre-index and 12-month follow-up periods).</p><p><strong>Results: </strong>The study included 177 patients (mean age 45.8 years; females 54.8%) with axSpA who initiated ixekizumab. Overall, 79.1% of patients reported prior biologic use; of these, 70.7% received tumor necrosis factor-alpha inhibitors (TNFi) and 49% received secukinumab. The mean (standard deviation [SD]) Charlson Comorbidity Index score was 1.1 (1.3) and ~ 27% of patients reported ≥2 comorbidities. The median (inter-quartile range [IQR]) number of ixekizumab prescription refills was 7 (4-11). The mean (SD) Proportion of Days Covered (PDC) for ixekizumab was 0.6 (0.3) and adherence (PDC ≥80%) was 34.5% (N = 61). Overall, 26.6% (N = 47) of patients switched to a non-index medication and 54.2% (N = 96) of patients discontinued ixekizumab. Among the patients who discontinued ixekizumab (N = 96), 19.8% (N = 19) restarted ixekizumab and 49.0% (N = 47) switched to a non-index medication. The median (IQR) ixekizumab persistence was 268 (120-366) days. Mean axSpA-related outpatient, inpatient, and emergency room visits were similar between the pre-index and follow-up periods. Treatment patterns were largely similar between biologic-experienced patients (N = 140; 79.1%) and the overall population.</p><p><strong>Conclusions: </strong>Despite high comorbidity burden and majority of the patients being biologic-experienced, patients initiating ixekizumab for axSpA showed favorable persistence profiles during the 12-month follow-up period.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"1333-1345"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 Bimekizumab in Patients with Psoriatic Arthritis: 2-Year Results from Two Phase 3 Studies.","authors":"Philip J Mease, Joseph F Merola, Yoshiya Tanaka, Laure Gossec, Iain B McInnes, Christopher T Ritchlin, Robert B M Landewé, Akihiko Asahina, Barbara Ink, Andrea Heinrichs, Rajan Bajracharya, Vishvesh Shende, Jason Coarse, Laura C Coates","doi":"10.1007/s40744-024-00708-8","DOIUrl":"10.1007/s40744-024-00708-8","url":null,"abstract":"<p><strong>Introduction: </strong>Psoriatic arthritis (PsA) is a chronic inflammatory disease requiring long-term treatment. Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated tolerability and sustained clinical efficacy for up to 1 year for patients with PsA. Here, we report the longer-‍term safety and efficacy of bimekizumab up to 2 years.</p><p><strong>Methods: </strong>BE OPTIMAL (biologic disease-modifying antirheumatic drug [bDMARD]-naïve) and BE COMPLETE (prior inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi-IR]) assessed subcutaneous bimekizumab 160 mg every 4 weeks in patients with PsA. BE OPTIMAL included a reference arm (adalimumab 40 mg every 2 weeks); patients switched to bimekizumab at week 52 with no washout between treatments. BE OPTIMAL week 52 and BE COMPLETE week 16 completers were eligible for the BE VITAL open-label extension. Efficacy outcomes are reported to week 104/100 (BE OPTIMAL/BE COMPLETE).</p><p><strong>Results: </strong>A total of 710/852 (83.3%) bDMARD-naïve and 322/400 (80.5%) TNFi-IR patients completed week 104/100. Up to 104 weeks, patients treated with bimekizumab in BE OPTIMAL and BE COMPLETE had treatment-emergent adverse event incidence rates (exposure-adjusted incidence rate/100 patient-years) of 179.9 (95% CI 166.9, 193.7) and 100.3 (89.2, ‍112.4), respectively. The proportion of patients achieving efficacy outcomes (≥ 50% improvement from baseline in American College of Rheumatology [ACR] response criteria, 100% improvement from baseline in Psorisis Area and Severity Index [PASI], minimal disease activity [MDA]) was sustained in all patients from week 52 to week 104/100.</p><p><strong>Conclusions: </strong>Bimekizumab was well tolerated for up to 2 years of treatment and no new safety signals were observed. Sustained clinical efficacy was observed up to 2 years in bDMARD-naïve and TNFi-IR patients with active PsA. Patients switching from adalimumab to bimekizumab demonstrated further improvement in skin and nail symptoms, and sustained efficacy in joint symptoms.</p><p><strong>Trial registration: </strong>BE OPTIMAL (NCT03895203), BE COMPLETE (NCT03896581), BE VITAL (NCT04009499).</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"1363-1382"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psoriatic Arthritis Acceptable Symptoms State: Does Sex Make a Difference?","authors":"Silvia Scriffignano, Fabio Massimo Perrotta, Mauro Fatica, Paola Conigliaro, Maria Sole Chimenti, Ennio Lubrano","doi":"10.1007/s40744-024-00698-7","DOIUrl":"10.1007/s40744-024-00698-7","url":null,"abstract":"<p><strong>Introduction: </strong>The Patient Acceptable Symptoms State (PASS) is a validated instrument that is used to assess whether a patient with psoriatic arthritis (PsA) accepts her/his disease status by asking them a simple question: \"Think about all the ways your PsA has affected you during the last 48 h. If you were to remain in the next few months as you were during the last 48 h, would this be acceptable to you?\" The aim of the present study was to explore any PASS differences in patients with PsA based on sex by looking at the corresponding thresholds of Disease Activity for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Impact of the Disease-12 (PsAID-12) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) in female and male patients.</p><p><strong>Methods: </strong>This was a cross-sectional study that included two PsA cohorts. To identify the DAPSA, PsAID and HAQ-DI thresholds that differentiated patients who reported \"yes\" in response to the PASS question from those who reported \"no,\" we used the receiver operating characteristic curves both for the female and male sexes. Moreover, Cohen's kappa test was used to determine the agreement of a PASS \"yes\" with DAPSA ≤ 14, PsAID ≤ 4 and HAQ-DI ≤ 0.5.</p><p><strong>Results: </strong>Three-hundred ten patients were considered for the study. The DAPSA, PsAID-12 and HAQ-DI thresholds that differentiated PASS \"yes\" patients from PASS \"no\" patients were 11.7, 1.85 and 0.625 in male patients and 13.3, 3.85 and 0.750 in female patients, respectively. A PASS \"yes\" and DAPSA ≤ 14 showed moderate agreement in males (kappa = 0.56) and good agreement in females (kappa = 0.80); the agreement between a PASS \"yes\" and PsAID ≤ 4 and between a PASS \"yes\" and HAQ-DI ≤ 0.5 was higher in female patients (moderate).</p><p><strong>Conclusion: </strong>Female patients accept their disease at higher DAPSA, PsAID and HAQ-DI values than male patients do. The clinical meaning of this could be that a female patient generally has a greater global disease acceptance inclination. Therefore, this study further supports the concept that sex differences are present in patients with PsA.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"1393-1402"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Over Activation of IL-6/STAT3 Signaling Pathway in Juvenile Dermatomyositis.","authors":"Qi Zheng, Zhaoling Wang, Yejun Tan, Kun Zhu, Meiping Lu","doi":"10.1007/s40744-024-00699-6","DOIUrl":"10.1007/s40744-024-00699-6","url":null,"abstract":"<p><strong>Introduction: </strong>Juvenile dermatomyositis (JDM) is characterized by persistent non-purulent inflammation in the muscle and skin. The underlying mechanisms still remain uncertain. This study aims to elucidate the mechanism of interleukin-6 (IL-6) activation of Janus kinase/signal transducer and activator of transcription 3 pathway (JAK/STAT3), contributing to the pathogenesis of JDM.</p><p><strong>Methods: </strong>Serum IL-6 levels were compared between 72 newly diagnosed patients with JDM and the same patient cohort in treatment remission. Single-cell RNA sequencing (scRNA-seq) was employed to identify differential signaling pathway expression in muscle biopsy samples from two patients with JDM and healthy controls. Immunohistochemistry was used to examine differences in STAT3 phosphorylation between JDM and control muscle tissues. In vitro, skeletal muscle cell lines were stimulated with IL-6, and the transcription levels of genes related to mitochondrial calcium channels were quantified via reverse transcription-polymerase chain reaction (RT-PCR). Reactive oxygen species (ROS) production was measured in both IL-6 treated and untreated groups. ROS levels were then compared between IL-6 receptor antagonist pre-treated skeletal muscle cells and untreated cells.</p><p><strong>Results: </strong>IL-6 levels in newly onset patients with JDM were significantly higher compared to the same patient cohort in remission states (p < 0.0001). Serum IL-6 was significantly increased in patients with negative myositis specific antibody (MSA), positive melanoma differentiation associated protein 5 (MDA5) and positive nuclear matrix protein 2 (NXP2), yet not for JDM with positive transcriptional intermediary factor γ (TIF1γ), based on subgroup analysis. ScRNA-seq analysis of muscle biopsies from patients with MDA5-positive JDM and patients with MSA negative JDM revealed abnormal activation of the JAK/STAT3 pathway in skeletal myocytes, macrophages, and vascular endothelial cells. The phosphorylation levels of STAT3 were elevated in active JDM cases. Transcription of the calcium channel modulation gene sarcolipin (SLN) was significantly higher in JDM primary skeletal muscle cells compared to normal cells. In vitro, IL-6 enhanced SLN transcription and induced ROS production, and blocking the IL-6 receptor resulted in decreased ROS generation in skeletal muscle cells.</p><p><strong>Conclusions: </strong>IL-6/JAK/STAT3 signaling pathway was abnormally activated in patients with JDM. IL-6 may be involved in the pathogenesis of muscle damage by triggering the development of calcium overload and production of ROS. Blockade of the IL-6/JAK/STAT3 pathway can be a potential treatment option for JDM, especially MDA5-positive patients and those who are negative for MSA.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"1255-1269"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Adalimumab-adbm Versus Adalimumab Reference Product on Patient-Reported Outcomes in Rheumatoid Arthritis: Results from VOLTAIRE-RA.","authors":"Vibeke Strand, Shaun Bender, Dorothy McCabe","doi":"10.1007/s40744-024-00687-w","DOIUrl":"10.1007/s40744-024-00687-w","url":null,"abstract":"<p><strong>Introduction: </strong>This post hoc analysis of VOLTAIRE-RA compared patient-reported outcomes, including health-related quality of life (HRQoL), in patients with rheumatoid arthritis (RA) before and after treatment with biosimilar adalimumab-adbm or adalimumab reference product.</p><p><strong>Methods: </strong>HRQoL was assessed by 36-Item Short Form Survey (SF-36) Physical and Mental Component Summary (PCS and MCS, respectively) and domain scores at baseline and weeks 12/24. Results were considered clinically meaningful if improvements were greater than or equal to minimum clinically important differences (MCIDs) of 2.5 for PCS and MCS and 5.0 for domain scores. Comparisons with age- and sex-matched norms and treatment-associated changes in domain scores from baseline were quantified using spydergrams and the health utility SF-6D measure. All comparisons between treatment groups were descriptive in nature.</p><p><strong>Results: </strong>No differences in PCS scores were reported between treatment groups at baseline or weeks 12/24. MCS scores slightly favored the reference product group at baseline, and differences in scores at weeks 12/24 generally reflected those differences. Improvements in PCS scores greater than or equal to MCID at weeks 12/24 were reported by over 65% of patients in both treatment groups, while over 56% experienced improvements in MCS scores greater than or equal to MCID at weeks 12/24. Similar proportions receiving reference product and adalimumab-adbm reported scores greater than or equal to US age- and sex-matched normative values at week 24: 14-39% versus 15-36%, respectively, compared with baseline (1-17%).</p><p><strong>Conclusion: </strong>In patients with moderate to severely active RA, adalimumab-adbm and adalimumab reference product were both associated with clinically meaningful improvements in SF-36 PCS, MCS, and domain scores that were highly similar at weeks 12/24. The high proportion of patients reporting scores greater than or equal to normative values in both treatment groups is notable, as this represents a treatment goal that was difficult to achieve in earlier RA trials. Video abstract available for this article.</p><p><strong>Trial registration: </strong>VOLTAIRE-RA (ClinicalTrials.gov number, NCT02137226; EudraCT number, 2012-002945-40). Video abstract (MP4 29755 KB).</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"1291-1302"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Filling the \"GAP\" in Real-World Assessment of Psoriatic Arthritis Disease Activity: Performance Characteristics of a Global/Pain Composite Endpoint.","authors":"William Tillett, Julie Birt, Aisha Vadhariya, Sarah Ross, Marcus Ngantcha, Khai Jing Ng","doi":"10.1007/s40744-024-00690-1","DOIUrl":"10.1007/s40744-024-00690-1","url":null,"abstract":"<p><strong>Introduction: </strong>Some retrospective data sources, such as electronic health records in the USA, report composite outcome measures not fully validated in psoriatic arthritis (PsA). However, they often contain global assessments, such as a Physician Global Assessment (PhGA) and Patient Global Assessment (PatGA), along with patient-reported pain scores, which individually are considered validated in PsA. This research described the performance characteristics of a 3-item global assessment and pain (GAP) composite endpoint using data from the ixekizumab phase 3 PsA clinical trial program.</p><p><strong>Methods: </strong>Discrimination of GAP was assessed by comparing placebo to active treatment arms. The magnitude of treatment effect and responsiveness were compared to Disease Activity Index for PsA (DAPSA), clinical DAPSA, DAPSA28, and Psoriatic Arthritis Disease Activity Score (PASDAS) using effect size (ES) and standardized response mean (SRM), respectively. Construct validity was evaluated through correlation among the composite endpoints, and with other physician- and patient-reported outcomes. Change in GAP was compared in patients who reached low disease activity (LDA) levels based on DAPSA, cDAPSA, and PASDAS vs those who did not.</p><p><strong>Results: </strong>GAP discriminated between active treatment and placebo with statistically significant separation as early as week 1. The largest ES/SRM was seen with GAP (2.29/1.74) and PASDAS (2.47/1.68). GAP had the strongest correlation with PASDAS (0.81-0.92) and showed moderate correlations with patient-assessed physical function, low correlations with physician-assessed skin and nail psoriasis, and low to moderate correlation with physician-assessed enthesitis. A significantly greater improvement in GAP was seen in the groups achieving LDA states compared to those not (p < 0.001).</p><p><strong>Conclusion: </strong>The GAP composite, an abbreviated endpoint comprising measures common in electronic health records, has promising performance characteristics and could be used to address important clinical questions regarding outcomes and impact of PsA in existing datasets. CLINTRIALS.</p><p><strong>Gov identifier: </strong>NCT01695239; NCT02349295.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"1101-1114"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Race on the Efficacy and Safety of Tofacitinib in Rheumatoid Arthritis: Post Hoc Analysis of Pooled Clinical Trials.","authors":"Grace C Wright, Eduardo Mysler, Kenneth Kwok, Mary Jane Cadatal, Rebecca Germino, Arne Yndestad, Cassandra D Kinch, Alexis Ogdie","doi":"10.1007/s40744-024-00677-y","DOIUrl":"10.1007/s40744-024-00677-y","url":null,"abstract":"<p><strong>Introduction: </strong>Racial disparities in disease activity, clinical outcomes, and treatment survival persist despite advancements in rheumatoid arthritis (RA) therapies and clinical management. In this post hoc analysis of pooled data from the tofacitinib global clinical program, we evaluated the impact of race on the efficacy and safety of tofacitinib in patients with RA.</p><p><strong>Methods: </strong>Data were pooled from 15 phase 2-3b/4 studies of patients with RA treated with tofacitinib 5 or 10 mg twice daily, adalimumab, or placebo. Outcomes were stratified by self-reported patient race (White/Black/Asian/Other). Efficacy outcomes to month 12 included: American College of Rheumatology (ACR)20/50/70 responses, Clinical Disease Activity Index (CDAI)/Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] low disease activity (LDA) rates, least squares (LS) mean change from baseline (∆) in CDAI, DAS28-4 (ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), and Pain [Visual Analog Scale (VAS)]. Odds ratios (ORs; 95% CI) versus placebo, and placebo-adjusted ∆LS means were calculated for active treatments using logistic regression model and mixed-effect model of repeated measurements, respectively. Safety outcomes were assessed throughout.</p><p><strong>Results: </strong>A total of 6355 patients were included (White, 4145; Black, 213; Asian, 1348; Other, 649). For tofacitinib-treated patients, ORs for ACR20/50/70 responses and CDAI/DAS28-4(ESR) LDA rates through month 3 were generally numerically higher for White/Asian/Other versus Black patients. Across active treatments, trends toward higher placebo-adjusted improvements from baseline in CDAI, DAS28-4 (ESR), HAQ-DI, and Pain (VAS) were observed in Asian/Other versus White/Black patients. Numerically higher placebo responses in Black versus White/Asian/Other patients were generally observed across outcomes through month 12. Safety outcomes were mostly similar across treatment/racial groups.</p><p><strong>Conclusions: </strong>In patients with RA, tofacitinib was efficacious across racial groups with similar safety outcomes; observed racial differences potentially reflect patient demographics or regional practice disparities.</p><p><strong>Trial registration numbers: </strong>ClinicalTrials.gov identifiers: NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01164579; NCT00976599; NCT01359150; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"1135-1164"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11422414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}