Pub Date : 2024-01-13DOI: 10.1007/s40744-023-00629-y
Alain Saraux, Licia Maria Henrique da Mota, Sanjay Dixit, Allan Gibofsky, Tsukasa Matsubara, Amy Mulvey, Cheryl Koehn, Mahta Mortezavi, Michelle Segovia, Meriem Kessouri
Introduction
The global coronavirus 2019 (COVID-19) pandemic created many challenges in healthcare provision. This study aimed to evaluate the global impact of the COVID-19 pandemic on people living with rheumatoid arthritis (RA).
Methods
The RA Narrative COVID-19 survey was conducted online among people with RA who resided in Brazil, Canada, France, Japan, and the US from August to September 2021. The survey examined disease management, healthcare access and experiences, and participant preferences for interactions with their doctor.
Results
Overall, 500 participants completed the survey: 100 each resided in Brazil, Canada, France, Japan, and the US. Emotional well-being was the aspect of disease management most reported to be negatively impacted by the pandemic (55% of participants); ‘having more anxiety and/or stress’ during the pandemic was the top factor that made controlling RA symptoms more difficult (49% of participants). In comparison, the top factor that made controlling RA symptoms easier was ‘having a less busy schedule’ (35% of participants). More participants had virtual appointments during versus pre-pandemic (53% vs. 13%, respectively) and participants were equally satisfied with the overall quality of care received via virtual and in-person appointments (76% of participants were ‘satisfied’ or ‘very satisfied’ with both). However, participants generally preferred in-person over virtual appointments, except for prescription refills, for which preferences were similar (39% vs. 36%, respectively).
Conclusions
This survey suggests that the COVID-19 pandemic did negatively impact some aspects of disease management for people living with RA but had positive impacts on the utilization of virtual care. Although participants generally preferred in-person appointments, these results position virtual care as an appropriate means for routine follow-ups.
导言2019年全球冠状病毒(COVID-19)大流行给医疗保健服务带来了许多挑战。本研究旨在评估 COVID-19 大流行对类风湿性关节炎(RA)患者的全球影响。方法于 2021 年 8 月至 9 月对居住在巴西、加拿大、法国、日本和美国的 RA 患者进行了 "RA Narrative COVID-19 调查"。调查内容包括疾病管理、医疗服务的获取和体验,以及参与者与医生互动的偏好:共有 500 名参与者完成了调查:巴西、加拿大、法国、日本和美国各 100 名。据报告,情绪健康是疾病管理中受大流行负面影响最大的方面(55% 的参与者);大流行期间 "焦虑和/或压力增加 "是导致 RA 症状更难控制的首要因素(49% 的参与者)。相比之下,使控制 RA 症状更容易的首要因素是 "日程不那么繁忙"(35% 的参与者)。与大流行前相比,更多参与者在大流行期间进行了虚拟预约(分别为 53% 和 13%),参与者对通过虚拟预约和面对面预约获得的整体护理质量同样满意(76% 的参与者对两者均表示 "满意 "或 "非常满意")。结论这项调查表明,COVID-19 大流行确实对 RA 患者疾病管理的某些方面产生了负面影响,但对虚拟医疗的利用产生了积极影响。虽然参与者普遍倾向于亲自预约,但这些结果将虚拟医疗定位为常规随访的一种适当手段。
{"title":"Impact of the COVID-19 Pandemic on People Living with Rheumatoid Arthritis: Experiences and Preferences in Accessing Healthcare Across Five Countries","authors":"Alain Saraux, Licia Maria Henrique da Mota, Sanjay Dixit, Allan Gibofsky, Tsukasa Matsubara, Amy Mulvey, Cheryl Koehn, Mahta Mortezavi, Michelle Segovia, Meriem Kessouri","doi":"10.1007/s40744-023-00629-y","DOIUrl":"https://doi.org/10.1007/s40744-023-00629-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>The global coronavirus 2019 (COVID-19) pandemic created many challenges in healthcare provision. This study aimed to evaluate the global impact of the COVID-19 pandemic on people living with rheumatoid arthritis (RA).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The RA Narrative COVID-19 survey was conducted online among people with RA who resided in Brazil, Canada, France, Japan, and the US from August to September 2021. The survey examined disease management, healthcare access and experiences, and participant preferences for interactions with their doctor.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Overall, 500 participants completed the survey: 100 each resided in Brazil, Canada, France, Japan, and the US. Emotional well-being was the aspect of disease management most reported to be negatively impacted by the pandemic (55% of participants); ‘having more anxiety and/or stress’ during the pandemic was the top factor that made controlling RA symptoms more difficult (49% of participants). In comparison, the top factor that made controlling RA symptoms easier was ‘having a less busy schedule’ (35% of participants). More participants had virtual appointments during versus pre-pandemic (53% vs. 13%, respectively) and participants were equally satisfied with the overall quality of care received via virtual and in-person appointments (76% of participants were ‘satisfied’ or ‘very satisfied’ with both). However, participants generally preferred in-person over virtual appointments, except for prescription refills, for which preferences were similar (39% vs. 36%, respectively).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>This survey suggests that the COVID-19 pandemic did negatively impact some aspects of disease management for people living with RA but had positive impacts on the utilization of virtual care. Although participants generally preferred in-person appointments, these results position virtual care as an appropriate means for routine follow-ups.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139463782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-18DOI: 10.1007/s40744-023-00627-0
Daniele Mauro, Giulio Forte, Denis Poddubnyy, Francesco Ciccia
Axial spondyloarthritis (axSpA) is a chronic, inflammatory rheumatic disease that primarily affects the axial skeleton, often inflicting severe pain, diminished mobility, and a compromised quality of life. The advent of Assessment of SpondyloArthritis international Society (ASAS) classification criteria for spondyloarthritis (SpA) have enabled the classification of patients with axSpA in the non-radiographic stage but poorly perform if mistakenly used for diagnostic purposes. Despite notable progress in early diagnosis facilitated by referral strategies and extensive magnetic resonance imaging (MRI) utilization, diagnostic delays persist as a concerning issue. This underscores the urgency to narrow the diagnostic gap and highlights the critical role of early diagnosis in mitigating the long-term structural damage associated with this condition. Research into the impact of non-steroidal anti-inflammatory drugs (NSAIDs) and biologic disease-modifying antirheumatic drugs (bDMARDs) on inflammatory symptoms and radiographic progression has been extensive. A compelling body of evidence suggests that early intervention leads to superior disease outcomes. However, most of these studies have centered on patients with established diseases rather than those in the early stages. Consequently, findings from studies on early pharmacological intervention remain inconclusive, and the potential for modifying the disease trajectory is still debatable. Without precise data from clinical trials, insights from basic science regarding the pathogenic mechanisms might point toward potential targets that warrant early intervention in the disease process. This review underscores the urgency of early diagnosis and intervention in axSpA, highlighting ongoing research gaps and the need for further exploration to improve patient outcomes.
{"title":"The Role of Early Treatment in the Management of Axial Spondyloarthritis: Challenges and Opportunities","authors":"Daniele Mauro, Giulio Forte, Denis Poddubnyy, Francesco Ciccia","doi":"10.1007/s40744-023-00627-0","DOIUrl":"https://doi.org/10.1007/s40744-023-00627-0","url":null,"abstract":"<p>Axial spondyloarthritis (axSpA) is a chronic, inflammatory rheumatic disease that primarily affects the axial skeleton, often inflicting severe pain, diminished mobility, and a compromised quality of life. The advent of Assessment of SpondyloArthritis international Society (ASAS) classification criteria for spondyloarthritis (SpA) have enabled the classification of patients with axSpA in the non-radiographic stage but poorly perform if mistakenly used for diagnostic purposes. Despite notable progress in early diagnosis facilitated by referral strategies and extensive magnetic resonance imaging (MRI) utilization, diagnostic delays persist as a concerning issue. This underscores the urgency to narrow the diagnostic gap and highlights the critical role of early diagnosis in mitigating the long-term structural damage associated with this condition. Research into the impact of non-steroidal anti-inflammatory drugs (NSAIDs) and biologic disease-modifying antirheumatic drugs (bDMARDs) on inflammatory symptoms and radiographic progression has been extensive. A compelling body of evidence suggests that early intervention leads to superior disease outcomes. However, most of these studies have centered on patients with established diseases rather than those in the early stages. Consequently, findings from studies on early pharmacological intervention remain inconclusive, and the potential for modifying the disease trajectory is still debatable. Without precise data from clinical trials, insights from basic science regarding the pathogenic mechanisms might point toward potential targets that warrant early intervention in the disease process. This review underscores the urgency of early diagnosis and intervention in axSpA, highlighting ongoing research gaps and the need for further exploration to improve patient outcomes.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138715437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-09DOI: 10.1007/s40744-023-00628-z
Megan M. Simonds, Samuel T. Freer, Lina Al-Jaberi, AnneMarie C. Brescia
Introduction
Fibroblast-like synoviocytes (FLS) play a critical role in inflammation that contributes to disease progression in juvenile idiopathic arthritis (JIA). In rheumatoid arthritis (RA), FLS express tumor necrosis factor alpha (TNFα). TNFα signaling has been shown to be upstream of transforming growth factor beta (TGFβ) signaling. Overexpression of TNFα and TGFβ, as well as related proteins, can cause increased inflammation in RA. In this study, we examine the effects of inhibiting TNFα signaling with adalimumab on FLS isolated from synovial fluid of patients with JIA.
Methods
Synovial fluid samples were selected from 41 patients in our repository. Of these samples, 23 were diagnosed with persistent oligoarticular JIA and 18 were diagnosed with extended oligoarticular JIA. All samples were taken prior to patients extending to a polyarticular course, or what we termed extended-to-be (ETB), and were on no medications or nonsteroidal anti-inflammatory drugs (NSAIDs) only at the time of arthrocentesis. For cell studies, FLS were isolated from synovial fluid and treated with adalimumab for 24 h. Protein antibody arrays were performed by RayBiotech, Inc. according to their protocols.
Results
In persistent FLS, TNFα (fold change [FC] = 1.2 p = 0.001), TGFβ (FC = 1.5 p = 0.001), lymphotoxin alpha (LTα) (FC = 4.3 p = 0.015), soluble tumor necrosis factor receptor 1 (sTNFRI) (FC = 5.1 p = 0.008), and soluble tumor necrosis factor receptor 2 (sTNFRII) (FC = 3.8 p = 0.025) were significantly elevated in adalimumab treated cells compared to untreated cells. In ETB FLS, TNFα was significantly elevated (FC = 1.04 p = 0.023) while TGFβ (FC = 1.03 p = 0.037) was significantly decreased in adalimumab-treated cells compared to untreated cells.
Conclusions
This data suggests that, after only 24 h, adalimumab is effective at decreasing inflammation that occurs downstream of initial TNFα signaling in extended-to-be fibroblast-like synoviocytes.
导言成纤维细胞样滑膜细胞(FLS)在炎症中起着至关重要的作用,而炎症会导致幼年特发性关节炎(JIA)的病情恶化。在类风湿性关节炎(RA)中,FLS表达肿瘤坏死因子α(TNFα)。TNFα 信号已被证明是转化生长因子β(TGFβ)信号的上游。TNFα和TGFβ以及相关蛋白的过度表达可导致RA炎症加剧。在本研究中,我们研究了用阿达木单抗抑制TNFα信号传导对从JIA患者滑液中分离出的FLS的影响。在这些样本中,23 例被诊断为持续性少关节型 JIA,18 例被诊断为扩展性少关节型 JIA。所有样本都是在患者发展为多关节病程之前采集的,也就是我们所说的扩展至关节病程(ETB),并且患者在关节穿刺时未服用任何药物或仅服用非甾体抗炎药(NSAIDs)。在细胞研究中,我们从滑液中分离出 FLS,并用阿达木单抗处理 24 小时。结果在持续性 FLS 中,TNFα(折叠变化 [FC] = 1.2 p = 0.001)、TGFβ(FC = 1.5 p = 0.001)、淋巴毒素α(LTα)(FC = 4.3 p = 0.015)、可溶性肿瘤坏死因子受体 1(sTNFRI)(FC = 5.1 p = 0.008)和可溶性肿瘤坏死因子受体 2(sTNFRII)(FC = 3.8 p = 0.025)在阿达木单抗处理过的细胞中比未经处理的细胞显著升高。在ETB FLS中,阿达木单抗处理的细胞与未处理的细胞相比,TNFα明显升高(FC = 1.04 p = 0.023),而TGFβ(FC = 1.03 p = 0.037)则明显降低。
{"title":"Adalimumab Effectively Decreases Inflammation Downstream of TNFα Signaling in Synoviocytes from Extended Oligoarticular Juvenile Idiopathic Arthritis","authors":"Megan M. Simonds, Samuel T. Freer, Lina Al-Jaberi, AnneMarie C. Brescia","doi":"10.1007/s40744-023-00628-z","DOIUrl":"https://doi.org/10.1007/s40744-023-00628-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Fibroblast-like synoviocytes (FLS) play a critical role in inflammation that contributes to disease progression in juvenile idiopathic arthritis (JIA). In rheumatoid arthritis (RA), FLS express tumor necrosis factor alpha (TNFα). TNFα signaling has been shown to be upstream of transforming growth factor beta (TGFβ) signaling. Overexpression of TNFα and TGFβ, as well as related proteins, can cause increased inflammation in RA. In this study, we examine the effects of inhibiting TNFα signaling with adalimumab on FLS isolated from synovial fluid of patients with JIA.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Synovial fluid samples were selected from 41 patients in our repository. Of these samples, 23 were diagnosed with persistent oligoarticular JIA and 18 were diagnosed with extended oligoarticular JIA. All samples were taken prior to patients extending to a polyarticular course, or what we termed extended-to-be (ETB), and were on no medications or nonsteroidal anti-inflammatory drugs (NSAIDs) only at the time of arthrocentesis. For cell studies, FLS were isolated from synovial fluid and treated with adalimumab for 24 h. Protein antibody arrays were performed by RayBiotech, Inc. according to their protocols.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In persistent FLS, TNFα (fold change [FC] = 1.2 <i>p</i> = 0.001), TGFβ (FC = 1.5 <i>p</i> = 0.001), lymphotoxin alpha (LTα) (FC = 4.3 <i>p</i> = 0.015), soluble tumor necrosis factor receptor 1 (sTNFRI) (FC = 5.1 <i>p</i> = 0.008), and soluble tumor necrosis factor receptor 2 (sTNFRII) (FC = 3.8 <i>p</i> = 0.025) were significantly elevated in adalimumab treated cells compared to untreated cells. In ETB FLS, TNFα was significantly elevated (FC = 1.04 <i>p</i> = 0.023) while TGFβ (FC = 1.03 <i>p</i> = 0.037) was significantly decreased in adalimumab-treated cells compared to untreated cells.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>This data suggests that, after only 24 h, adalimumab is effective at decreasing inflammation that occurs downstream of initial TNFα signaling in extended-to-be fibroblast-like synoviocytes.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138561739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-01Epub Date: 2023-09-11DOI: 10.1007/s40744-023-00589-3
Stephanie G Werner, Xenofon Baraliakos, Sabine Reckert, Martin Bohl-Bühler, Marie-Claude Laliberté, Tanya Girard, Katharina Jeromin, Nikola Baschuk, Björn Fritz, Louis Bessette, Axel J Hueber
Introduction: Our aim was to investigate the efficacy and safety of upadacitinib (UPA) in patients with either oligo- or polyarticular active psoriatic arthritis (PsA) using routine clinical practice data from an observational, prospective, multicentre study.
Methods: This interim analysis contains upadacitinib efficacy and safety data from the UPJOINT study, collected from baseline to the week 24 visit with a focus on composite measures, clinical assessments and patient-reported outcomes, amongst others, including minimal disease activity (MDA), very low disease activity (VLDA), Disease Activity Index for Psoriatic Arthritis (DAPSA), Leeds Enthesitis Index (LEI), resolution of dactylitis and nail psoriasis and body surface area affected by skin psoriasis (BSA).
Results: A total of 296 patients with baseline data and 192 with completed week 24 visits were included in the analysis. The proportion of patients achieving MDA increased from 2.7% at baseline to 39.1% at week 24 (95% CI 32.1, 46.3). Similarly, the number of patients in DAPSA remission (DAPSA ≤ 4) increased from 0 at baseline to 32 (16.7%) by week 24. At that time, 59.4% of the patients were either in DAPSA remission or had low disease activity (DAPSA ≤ 14). During the 24 weeks time frame, the proportion of patients with BSA ≤ 3 increased from 80.7% to 91.1%. Furthermore, at weeks 12 and 24, 45.14% and 47.19% of affected patients showed a resolution of enthesitis. Active dactylitis and nail psoriasis at baseline were reported to affect 10.5% and 22.0%, decreasing to 2.6% and 5.7% at week 24, respectively. The safety findings are consistent with the known safety profile of upadacitinib in rheumatoid arthritis and PsA; no new safety risks were identified.
Conclusion: The data from this study confirm the findings of previous randomized controlled trials suggesting UPA is an effective treatment for active PsA without any new safety signals in patients from daily clinical practice.
我们的目的是通过一项观察性、前瞻性、多中心研究的常规临床实践数据,研究upadacitinib (UPA)对寡关节或多关节活动性银屑病关节炎(PsA)患者的疗效和安全性。方法:该中期分析包含UPJOINT研究的upadacitinib疗效和安全性数据,从基线收集到第24周访问,重点是复合测量、临床评估和患者报告的结果,其中包括最小疾病活动性(MDA)、极低疾病活动性(VLDA)、银屑病关节炎疾病活动性指数(DAPSA)、利兹关节炎指数(LEI)、手指炎和指甲银屑病的缓解和皮肤银屑病(BSA)影响的体表面积。结果:共有296名基线患者和192名完成第24周就诊的患者被纳入分析。达到MDA的患者比例从基线时的2.7%增加到第24周时的39.1% (95% CI 32.1, 46.3)。同样,DAPSA缓解(DAPSA≤4)的患者数量从基线时的0例增加到第24周时的32例(16.7%)。当时,59.4%的患者处于DAPSA缓解期或疾病活动性较低(DAPSA≤14)。在24周的时间框架内,BSA≤3的患者比例从80.7%上升到91.1%。此外,在第12周和第24周,45.14%和47.19%的患者表现出肠炎的消退。据报道,活动性指炎和甲癣在基线时影响10.5%和22.0%,在第24周分别下降到2.6%和5.7%。安全性研究结果与upadacitinib治疗类风湿关节炎和PsA的已知安全性一致;没有发现新的安全风险。结论:本研究的数据证实了先前随机对照试验的发现,表明UPA是治疗活动性PsA的有效方法,在日常临床实践中没有任何新的安全性信号。临床试验注册:ClinicalTrials.gov识别码,NCT04758117。
{"title":"Treatment with Upadacitinib in Active Psoriatic Arthritis: Efficacy and Safety Data of the First 192 Patients from the UPJOINT Study, a Multicentre, Observational Study in Clinical Practice.","authors":"Stephanie G Werner, Xenofon Baraliakos, Sabine Reckert, Martin Bohl-Bühler, Marie-Claude Laliberté, Tanya Girard, Katharina Jeromin, Nikola Baschuk, Björn Fritz, Louis Bessette, Axel J Hueber","doi":"10.1007/s40744-023-00589-3","DOIUrl":"10.1007/s40744-023-00589-3","url":null,"abstract":"<p><strong>Introduction: </strong>Our aim was to investigate the efficacy and safety of upadacitinib (UPA) in patients with either oligo- or polyarticular active psoriatic arthritis (PsA) using routine clinical practice data from an observational, prospective, multicentre study.</p><p><strong>Methods: </strong>This interim analysis contains upadacitinib efficacy and safety data from the UPJOINT study, collected from baseline to the week 24 visit with a focus on composite measures, clinical assessments and patient-reported outcomes, amongst others, including minimal disease activity (MDA), very low disease activity (VLDA), Disease Activity Index for Psoriatic Arthritis (DAPSA), Leeds Enthesitis Index (LEI), resolution of dactylitis and nail psoriasis and body surface area affected by skin psoriasis (BSA).</p><p><strong>Results: </strong>A total of 296 patients with baseline data and 192 with completed week 24 visits were included in the analysis. The proportion of patients achieving MDA increased from 2.7% at baseline to 39.1% at week 24 (95% CI 32.1, 46.3). Similarly, the number of patients in DAPSA remission (DAPSA ≤ 4) increased from 0 at baseline to 32 (16.7%) by week 24. At that time, 59.4% of the patients were either in DAPSA remission or had low disease activity (DAPSA ≤ 14). During the 24 weeks time frame, the proportion of patients with BSA ≤ 3 increased from 80.7% to 91.1%. Furthermore, at weeks 12 and 24, 45.14% and 47.19% of affected patients showed a resolution of enthesitis. Active dactylitis and nail psoriasis at baseline were reported to affect 10.5% and 22.0%, decreasing to 2.6% and 5.7% at week 24, respectively. The safety findings are consistent with the known safety profile of upadacitinib in rheumatoid arthritis and PsA; no new safety risks were identified.</p><p><strong>Conclusion: </strong>The data from this study confirm the findings of previous randomized controlled trials suggesting UPA is an effective treatment for active PsA without any new safety signals in patients from daily clinical practice.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier, NCT04758117.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10194450","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}
Introduction: Patients with adult-onset Still's disease (AOSD) are at risk of developing macrophage activation syndrome (MAS), a life-threatening condition. Some cases of MAS have been reported following the use of biological agents, highlighting the need to identify contributing factors. This study aims to examine the characteristics of MAS in patients with AOSD treated with anakinra (ANA) or tocilizumab (TCZ).
Methods: A systematic search was conducted across four online databases to identify studies reporting the incidence rates of MAS in patients with AOSD treated with ANA or TCZ. Meta-analysis was performed using a random-effects model and the generic inverse variance method to estimate the pooled incidence rates. The difference in incidence rates of MAS between TCZ and ANA was assessed. Additionally, we analyzed laboratory data and clinical features of AOSD cases at our institution, stratifying them into two groups: those who developed MAS after TCZ administration and those who did not.
Results: Of the 455 screened articles, we included five ANA and six TCZ studies. The pooled incidence rates of MAS were 1.50% (95% confidence interval [CI], 0-3.36) for ANA (345 patients) and 14.01% (95% CI 4.51-23.51) for TCZ (94 patients). MAS incidence was significantly higher in the TCZ group (P = 0.01). Among the 17 patients from our institution, the six patients who developed MAS had significantly higher white blood cell and neutrophil counts, as well as elevated levels of lactate dehydrogenase, C-reactive protein, and ferritin before TCZ induction (P < 0.05).
Conclusions: In patients with AOSD, the manifestation of MAS is influenced by multiple causative factors. Consequently, the administration of TCZ should be approached with caution, particularly in patients exhibiting elevated inflammatory markers.
Trial registration: This study was registered with the Clinical Trial Registry of the University Hospital Medical Information Network (Japan) as UMIN000049243.
{"title":"Risk of Macrophage Activation Syndrome in Patients with Adult-Onset Still's Disease Treated with IL-1 and IL-6 Inhibitors: A Meta-analysis and Single-Center Experience.","authors":"Soichiro Adachi, Kaoru Takase-Minegishi, Ayaka Maeda, Hideto Nagai, Nobuyuki Horita, Ryusuke Yoshimi, Yohei Kirino, Hideaki Nakajima","doi":"10.1007/s40744-023-00600-x","DOIUrl":"10.1007/s40744-023-00600-x","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with adult-onset Still's disease (AOSD) are at risk of developing macrophage activation syndrome (MAS), a life-threatening condition. Some cases of MAS have been reported following the use of biological agents, highlighting the need to identify contributing factors. This study aims to examine the characteristics of MAS in patients with AOSD treated with anakinra (ANA) or tocilizumab (TCZ).</p><p><strong>Methods: </strong>A systematic search was conducted across four online databases to identify studies reporting the incidence rates of MAS in patients with AOSD treated with ANA or TCZ. Meta-analysis was performed using a random-effects model and the generic inverse variance method to estimate the pooled incidence rates. The difference in incidence rates of MAS between TCZ and ANA was assessed. Additionally, we analyzed laboratory data and clinical features of AOSD cases at our institution, stratifying them into two groups: those who developed MAS after TCZ administration and those who did not.</p><p><strong>Results: </strong>Of the 455 screened articles, we included five ANA and six TCZ studies. The pooled incidence rates of MAS were 1.50% (95% confidence interval [CI], 0-3.36) for ANA (345 patients) and 14.01% (95% CI 4.51-23.51) for TCZ (94 patients). MAS incidence was significantly higher in the TCZ group (P = 0.01). Among the 17 patients from our institution, the six patients who developed MAS had significantly higher white blood cell and neutrophil counts, as well as elevated levels of lactate dehydrogenase, C-reactive protein, and ferritin before TCZ induction (P < 0.05).</p><p><strong>Conclusions: </strong>In patients with AOSD, the manifestation of MAS is influenced by multiple causative factors. Consequently, the administration of TCZ should be approached with caution, particularly in patients exhibiting elevated inflammatory markers.</p><p><strong>Trial registration: </strong>This study was registered with the Clinical Trial Registry of the University Hospital Medical Information Network (Japan) as UMIN000049243.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41135020","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}
Pub Date : 2023-12-01Epub Date: 2023-09-27DOI: 10.1007/s40744-023-00598-2
Xuan Huang, Qing Shu, Xuemei Luo, Weihong Ge, Han Xie, Yujie Zhou
Introduction: The aim of this study was to determine the factors associated with the concentrations of hydroxychloroquine (HCQ) and its major metabolite, desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE).
Methods: Patients with SLE taking oral HCQ for at least 3 months were recruited from the Department of Rheumatology and Immunology of Nanjing Drum Tower Hospital. Clinical characteristics and laboratory values were examined. The concentrations of HCQ and DHCQ were measured by high-performance liquid chromatography, and the effects of various factors on the concentrations were investigated.
Results: A total of 272 patients were included in this study. The average concentration of HCQ was 690.90 ng/ml and the average concentration of DHCQ was 431.84 ng/ml. Multivariate analysis indicated that gender (P = 0.015), age (year) (P < 0.001), weight (kg) (P = 0.013), duration of HCQ use (month) (P < 0.001), systemic lupus erythematosus disease activity index (SLEDAI) (P < 0.001), platelet count (× 109/l) (P < 0.001), immunoglobulin G levels (g/l) (P = 0.014) were associated with low HCQ concentrations. Gender (P = 0.006), duration of HCQ use (month) (P < 0.001), SLEDAI (P = 0.007), and platelet count (× 109/l) (P < 0.001) were associated with low DHCQ concentrations.
Conclusions: Patients with SLE require long-term administration of HCQ, but blood levels vary widely between individuals. Studying the factors influencing the blood HCQ and DHCQ concentrations and optimizing the dose according to individual characteristics might help to improve the efficacy of HCQ.
{"title":"Analysis of Factors Influencing Whole Blood Hydroxychloroquine Concentration in Patients with Systemic Lupus Erythematosus in China.","authors":"Xuan Huang, Qing Shu, Xuemei Luo, Weihong Ge, Han Xie, Yujie Zhou","doi":"10.1007/s40744-023-00598-2","DOIUrl":"10.1007/s40744-023-00598-2","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this study was to determine the factors associated with the concentrations of hydroxychloroquine (HCQ) and its major metabolite, desethylhydroxychloroquine (DHCQ), in patients with systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>Patients with SLE taking oral HCQ for at least 3 months were recruited from the Department of Rheumatology and Immunology of Nanjing Drum Tower Hospital. Clinical characteristics and laboratory values were examined. The concentrations of HCQ and DHCQ were measured by high-performance liquid chromatography, and the effects of various factors on the concentrations were investigated.</p><p><strong>Results: </strong>A total of 272 patients were included in this study. The average concentration of HCQ was 690.90 ng/ml and the average concentration of DHCQ was 431.84 ng/ml. Multivariate analysis indicated that gender (P = 0.015), age (year) (P < 0.001), weight (kg) (P = 0.013), duration of HCQ use (month) (P < 0.001), systemic lupus erythematosus disease activity index (SLEDAI) (P < 0.001), platelet count (× 10<sup>9</sup>/l) (P < 0.001), immunoglobulin G levels (g/l) (P = 0.014) were associated with low HCQ concentrations. Gender (P = 0.006), duration of HCQ use (month) (P < 0.001), SLEDAI (P = 0.007), and platelet count (× 10<sup>9</sup>/l) (P < 0.001) were associated with low DHCQ concentrations.</p><p><strong>Conclusions: </strong>Patients with SLE require long-term administration of HCQ, but blood levels vary widely between individuals. Studying the factors influencing the blood HCQ and DHCQ concentrations and optimizing the dose according to individual characteristics might help to improve the efficacy of HCQ.</p><p><strong>Trial registration: </strong>ChiCTR2300070628.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41149215","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}
Pub Date : 2023-12-01Epub Date: 2023-10-04DOI: 10.1007/s40744-023-00593-7
Cory Perugino, Emma L Culver, Arezou Khosroshahi, Wen Zhang, Emanuel Della-Torre, Kazuichi Okazaki, Yoshiya Tanaka, Matthias Löhr, Nicolas Schleinitz, Judith Falloon, Dewei She, Daniel Cimbora, John H Stone
Introduction: Immunoglobulin G4-related disease (IgG4-RD) is a debilitating multiorgan disease characterized by recurring flares leading to organ dysfunction, decreased quality of life, and mortality. Glucocorticoids, the standard of care for IgG4-RD, are associated with substantial treatment-related toxicity. Inebilizumab, an antibody directed against CD19, mediates the rapid and durable depletion of CD19+ B cells thought to be involved in IgG4-RD pathogenesis. We describe the first international, prospective, double-blind, placebo-controlled trial to evaluate the safety and efficacy of B-cell depletion for flare prevention in IgG4-RD (MITIGATE).
Methods: The study was designed by an international panel of physicians with expertise in IgG4-RD. Critical trial design decisions included the selection of participants, definition of clinically meaningful primary and secondary endpoints, accommodation of standard of care, and development of flare diagnostic criteria. The study is approved for conduct in 22 countries.
Planned outcomes: The primary efficacy endpoint is time from randomization to the occurrence of the first centrally adjudicated and investigator-treated disease flare during the 1-year randomized controlled period. A set of novel, organ-specific flare diagnostic criteria were developed specifically for this trial, incorporating symptoms and signs, laboratory findings, imaging study results, and pathology data. MITIGATE aims to accrue 39 flares for the primary endpoint, which provides sufficient power to detect a relative risk reduction of 65% in the inebilizumab group. It is anticipated that enrollment of 160 participants will achieve this goal. Additional endpoints include safety, annualized flare rate, flare-free complete remission, quality-of-life measures, and cumulative glucocorticoid use. MITIGATE represents the first randomized, double-blind, placebo-controlled trial of any treatment strategy conducted in IgG4-RD. Data from this study will provide insights into the natural history and pathophysiology of IgG4-RD and the efficacy and safety of B-cell depletion as a therapeutic avenue.
{"title":"Efficacy and Safety of Inebilizumab in IgG4-Related Disease: Protocol for a Randomized Controlled Trial.","authors":"Cory Perugino, Emma L Culver, Arezou Khosroshahi, Wen Zhang, Emanuel Della-Torre, Kazuichi Okazaki, Yoshiya Tanaka, Matthias Löhr, Nicolas Schleinitz, Judith Falloon, Dewei She, Daniel Cimbora, John H Stone","doi":"10.1007/s40744-023-00593-7","DOIUrl":"10.1007/s40744-023-00593-7","url":null,"abstract":"<p><strong>Introduction: </strong>Immunoglobulin G4-related disease (IgG4-RD) is a debilitating multiorgan disease characterized by recurring flares leading to organ dysfunction, decreased quality of life, and mortality. Glucocorticoids, the standard of care for IgG4-RD, are associated with substantial treatment-related toxicity. Inebilizumab, an antibody directed against CD19, mediates the rapid and durable depletion of CD19<sup>+</sup> B cells thought to be involved in IgG4-RD pathogenesis. We describe the first international, prospective, double-blind, placebo-controlled trial to evaluate the safety and efficacy of B-cell depletion for flare prevention in IgG4-RD (MITIGATE).</p><p><strong>Methods: </strong>The study was designed by an international panel of physicians with expertise in IgG4-RD. Critical trial design decisions included the selection of participants, definition of clinically meaningful primary and secondary endpoints, accommodation of standard of care, and development of flare diagnostic criteria. The study is approved for conduct in 22 countries.</p><p><strong>Planned outcomes: </strong>The primary efficacy endpoint is time from randomization to the occurrence of the first centrally adjudicated and investigator-treated disease flare during the 1-year randomized controlled period. A set of novel, organ-specific flare diagnostic criteria were developed specifically for this trial, incorporating symptoms and signs, laboratory findings, imaging study results, and pathology data. MITIGATE aims to accrue 39 flares for the primary endpoint, which provides sufficient power to detect a relative risk reduction of 65% in the inebilizumab group. It is anticipated that enrollment of 160 participants will achieve this goal. Additional endpoints include safety, annualized flare rate, flare-free complete remission, quality-of-life measures, and cumulative glucocorticoid use. MITIGATE represents the first randomized, double-blind, placebo-controlled trial of any treatment strategy conducted in IgG4-RD. Data from this study will provide insights into the natural history and pathophysiology of IgG4-RD and the efficacy and safety of B-cell depletion as a therapeutic avenue.</p><p><strong>Trial registration: </strong>NCT04540497.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41149614","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}
Pub Date : 2023-12-01Epub Date: 2023-10-30DOI: 10.1007/s40744-023-00604-7
Mark S Fineman, Timothy E McAlindon, Christian Lattermann, Christopher J Swearingen, Sarah Kennedy, Victor A Lopez, Ismail Simsek, Jeyanesh R S Tambiah, Yusuf Yazici
Introduction: Knee osteoarthritis (OA) is a common painful disorder. Intra-articular (IA) corticosteroid injections are frequently prescribed to treat knee pain. Lorecivivint (LOR), a novel IA cdc2-Like Kinase (CLK)/Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase (DYRK) inhibitor thought to modulate Wnt and inflammatory pathways, has appeared safe and demonstrated improved patient-reported outcomes compared with placebo. While LOR is proposed for stand-alone use, in clinical practice, providers might administer LOR in close time proximity to IA corticosteroid. This open-label, parallel-arm, healthy volunteer study assessed potential short-term safety, tolerability and pharmacokinetic (PK) interactions between IA LOR and triamcinolone acetonide (TCA) administered 7 days apart.
Methods: Healthy volunteers were randomized to Treatment Sequence 1 (IA 40 mg TCA followed by IA 0.07 mg LOR) or Treatment Sequence 2 (IA 0.07 mg LOR followed by IA 40 mg TCA). Treatment-emergent adverse events (TEAEs) were categorized by "epoch", with epoch 1 spanning from first until second injection, and epoch 2 spanning from second injection until end of study. Plasma PK was assessed pre injection and out to 22 days after to assess PK treatment interaction.
Results: A total of 18 TEAEs were reported by 11 (27.5%) of 40 enrolled participants, and there were no serious adverse events. Thirteen TEAEs were reported in Treatment Sequence 1 and five in Treatment Sequence 2, similarly distributed between epochs 1 and 2. In all participants and at all time points, plasma LOR concentrations were below the limit of quantification (0.100 ng/mL). Geometric mean concentrations and PK parameters for TCA were similar between treatment sequences.
Conclusion: No safety signals were observed. There were no quantifiable plasma concentrations of LOR in either Treatment Sequence. The PK of TCA was unaffected by previous LOR injection. These results suggest that IA administration of LOR and TCA in close time proximity is unlikely to pose a safety concern.
{"title":"Safety, Tolerability, and Pharmacokinetics of Same-Knee Intra-Articular Injection of Corticosteroid and Lorecivivint Within 7 Days: An Open-Label, Randomized, Parallel-Arm Study.","authors":"Mark S Fineman, Timothy E McAlindon, Christian Lattermann, Christopher J Swearingen, Sarah Kennedy, Victor A Lopez, Ismail Simsek, Jeyanesh R S Tambiah, Yusuf Yazici","doi":"10.1007/s40744-023-00604-7","DOIUrl":"10.1007/s40744-023-00604-7","url":null,"abstract":"<p><strong>Introduction: </strong>Knee osteoarthritis (OA) is a common painful disorder. Intra-articular (IA) corticosteroid injections are frequently prescribed to treat knee pain. Lorecivivint (LOR), a novel IA cdc2-Like Kinase (CLK)/Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase (DYRK) inhibitor thought to modulate Wnt and inflammatory pathways, has appeared safe and demonstrated improved patient-reported outcomes compared with placebo. While LOR is proposed for stand-alone use, in clinical practice, providers might administer LOR in close time proximity to IA corticosteroid. This open-label, parallel-arm, healthy volunteer study assessed potential short-term safety, tolerability and pharmacokinetic (PK) interactions between IA LOR and triamcinolone acetonide (TCA) administered 7 days apart.</p><p><strong>Methods: </strong>Healthy volunteers were randomized to Treatment Sequence 1 (IA 40 mg TCA followed by IA 0.07 mg LOR) or Treatment Sequence 2 (IA 0.07 mg LOR followed by IA 40 mg TCA). Treatment-emergent adverse events (TEAEs) were categorized by \"epoch\", with epoch 1 spanning from first until second injection, and epoch 2 spanning from second injection until end of study. Plasma PK was assessed pre injection and out to 22 days after to assess PK treatment interaction.</p><p><strong>Results: </strong>A total of 18 TEAEs were reported by 11 (27.5%) of 40 enrolled participants, and there were no serious adverse events. Thirteen TEAEs were reported in Treatment Sequence 1 and five in Treatment Sequence 2, similarly distributed between epochs 1 and 2. In all participants and at all time points, plasma LOR concentrations were below the limit of quantification (0.100 ng/mL). Geometric mean concentrations and PK parameters for TCA were similar between treatment sequences.</p><p><strong>Conclusion: </strong>No safety signals were observed. There were no quantifiable plasma concentrations of LOR in either Treatment Sequence. The PK of TCA was unaffected by previous LOR injection. These results suggest that IA administration of LOR and TCA in close time proximity is unlikely to pose a safety concern.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT04598542.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413769","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}
Pub Date : 2023-12-01Epub Date: 2023-09-27DOI: 10.1007/s40744-023-00597-3
Rieke Alten, Gerd R Burmester, Marco Matucci-Cerinic, Jean-Hugues Salmon, Andrew Östör, Khai Jing Ng, Jens Gerwien, Liliana Zaremba-Pechmann, Alan J M Brnabic, Bruno Fautrel
Introduction: RA-BE-REAL is a 3-year, multinational, prospective, observational study of adult patients with rheumatoid arthritis (RA) evaluating time to discontinuation of initial RA treatment along with patient baseline characteristics. This study's primary objective was to assess the time to discontinuation of initial baricitinib, any other targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD), or any biologic disease-modifying anti-rheumatic drug (bDMARD) treatment for all causes (excluding sustained clinical response) over 24 months in a European population.
Methods: Patients initiated treatment with baricitinib (cohort A) or any bDMARD or tsDMARD (cohort B) for the first time. This study's primary objective was to assess the time to discontinuation of initial baricitinib, any other targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD), or any biologic disease-modifying anti-rheumatic drug (bDMARD) treatment for all causes (excluding sustained clinical response) over 24 months in a European population. Comparative effectiveness analyses, over 24 months, included time to treatment discontinuation for all causes (excluding sustained clinical response), percentage of patients achieving Clinical Disease Activity Index (CDAI) remission or low disease activity (LDA), as well as mean changes from baseline for CDAI, pain visual analogue scale, and the Health Assessment Questionnaire-Disability Index (HAQ-DI). For this European subpopulation, comparative analyses were performed using a frequentist model averaging (FMA) framework based on a data-driven machine learning causal inference approach to compare time to discontinuation, effectiveness, rates of remission or LDA, and patient-reported outcomes over 24 months comparing baricitinib with TNFi, as well as non-TNFi and tsDMARD grouped as other mechanism of action (OMA) drugs.
Results: In the European sample of RA-BE-REAL, patients with RA treated with baricitinib experienced fewer discontinuations in comparison to those treated with tumour necrosis factor inhibitors or OMA. Overall, patients naïve to b/tsDMARDs achieved a higher rate of LDA and remission compared with experienced patients. A significantly greater proportion of patients treated with baricitinib achieved LDA compared with b/tsDMARDs.
Conclusion: This real-world data can better inform clinicians about baricitinib effectiveness and drug survival when prescribing treatment for patients with RA across different subpopulations.
{"title":"Comparative Effectiveness, Time to Discontinuation, and Patient-Reported Outcomes with Baricitinib in Rheumatoid Arthritis: 2-Year Data from the Multinational, Prospective Observational RA-BE-REAL Study in European Patients.","authors":"Rieke Alten, Gerd R Burmester, Marco Matucci-Cerinic, Jean-Hugues Salmon, Andrew Östör, Khai Jing Ng, Jens Gerwien, Liliana Zaremba-Pechmann, Alan J M Brnabic, Bruno Fautrel","doi":"10.1007/s40744-023-00597-3","DOIUrl":"10.1007/s40744-023-00597-3","url":null,"abstract":"<p><strong>Introduction: </strong>RA-BE-REAL is a 3-year, multinational, prospective, observational study of adult patients with rheumatoid arthritis (RA) evaluating time to discontinuation of initial RA treatment along with patient baseline characteristics. This study's primary objective was to assess the time to discontinuation of initial baricitinib, any other targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD), or any biologic disease-modifying anti-rheumatic drug (bDMARD) treatment for all causes (excluding sustained clinical response) over 24 months in a European population.</p><p><strong>Methods: </strong>Patients initiated treatment with baricitinib (cohort A) or any bDMARD or tsDMARD (cohort B) for the first time. This study's primary objective was to assess the time to discontinuation of initial baricitinib, any other targeted synthetic disease-modifying anti-rheumatic drug (tsDMARD), or any biologic disease-modifying anti-rheumatic drug (bDMARD) treatment for all causes (excluding sustained clinical response) over 24 months in a European population. Comparative effectiveness analyses, over 24 months, included time to treatment discontinuation for all causes (excluding sustained clinical response), percentage of patients achieving Clinical Disease Activity Index (CDAI) remission or low disease activity (LDA), as well as mean changes from baseline for CDAI, pain visual analogue scale, and the Health Assessment Questionnaire-Disability Index (HAQ-DI). For this European subpopulation, comparative analyses were performed using a frequentist model averaging (FMA) framework based on a data-driven machine learning causal inference approach to compare time to discontinuation, effectiveness, rates of remission or LDA, and patient-reported outcomes over 24 months comparing baricitinib with TNFi, as well as non-TNFi and tsDMARD grouped as other mechanism of action (OMA) drugs.</p><p><strong>Results: </strong>In the European sample of RA-BE-REAL, patients with RA treated with baricitinib experienced fewer discontinuations in comparison to those treated with tumour necrosis factor inhibitors or OMA. Overall, patients naïve to b/tsDMARDs achieved a higher rate of LDA and remission compared with experienced patients. A significantly greater proportion of patients treated with baricitinib achieved LDA compared with b/tsDMARDs.</p><p><strong>Conclusion: </strong>This real-world data can better inform clinicians about baricitinib effectiveness and drug survival when prescribing treatment for patients with RA across different subpopulations.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41111222","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}
Introduction: The efficacy and safety of ixekizumab, an anti-interleukin-17A antibody, in patients with severe symptoms of psoriatic arthritis are largely unexplored. We report the efficacy and safety of ixekizumab in a post hoc analysis of the SPIRIT-P1 trial.
Methods: Patients were treated with placebo, ixekizumab 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), or adalimumab 40 mg Q2W for 24 weeks. In this subgroup analysis of SPIRIT-P1, the population with severe psoriatic arthritis was defined using the modified composite psoriatic activity index total score > 7 and peripheral arthritis score = 3 (> 4 tender or swollen joint count and ≥ 0.5 Health Assessment Questionnaire-Disability Index). Efficacy was measured by joint and skin endpoints including disease progression.
Results: In the severe population, significantly more patients (p ≤ 0.001) treated with ixekizumab than placebo achieved 20% improvement according to the American College of Rheumatology criteria (ACR 20): 63.3% for ixekizumab Q4W, 60.4% for ixekizumab Q2W, and 24.5% for placebo. Statistically greater responses compared with placebo were observed in the severe population for ACR 50, ACR 70, ACR core set, disease activity index for psoriatic arthritis (DAPSA) low disease activity and DAPSA remission, and 28-joint disease activity score using C-reactive protein, as well as Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100 (p ≤ 0.001). Efficacy findings and the safety profile of ixekizumab in the severe population were consistent with those of the overall population, with no new safety concerns identified.
Conclusions: In patients with severe psoriatic arthritis, 24 weeks of treatment with ixekizumab resulted in improvements in both joint and skin symptoms. The safety profile in the severe population was consistent with the established safety profile of ixekizumab.
{"title":"Ixekizumab Efficacy in Patients with Severe Peripheral Psoriatic Arthritis: A Post Hoc Analysis of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (SPIRIT-P1).","authors":"Hideto Kameda, Kohei Hagimori, Yoji Morisaki, Thorsten Holzkämper, Ayako Konomi, Hiroaki Dobashi","doi":"10.1007/s40744-023-00605-6","DOIUrl":"10.1007/s40744-023-00605-6","url":null,"abstract":"<p><strong>Introduction: </strong>The efficacy and safety of ixekizumab, an anti-interleukin-17A antibody, in patients with severe symptoms of psoriatic arthritis are largely unexplored. We report the efficacy and safety of ixekizumab in a post hoc analysis of the SPIRIT-P1 trial.</p><p><strong>Methods: </strong>Patients were treated with placebo, ixekizumab 80 mg every 2 weeks (Q2W) or 4 weeks (Q4W), or adalimumab 40 mg Q2W for 24 weeks. In this subgroup analysis of SPIRIT-P1, the population with severe psoriatic arthritis was defined using the modified composite psoriatic activity index total score > 7 and peripheral arthritis score = 3 (> 4 tender or swollen joint count and ≥ 0.5 Health Assessment Questionnaire-Disability Index). Efficacy was measured by joint and skin endpoints including disease progression.</p><p><strong>Results: </strong>In the severe population, significantly more patients (p ≤ 0.001) treated with ixekizumab than placebo achieved 20% improvement according to the American College of Rheumatology criteria (ACR 20): 63.3% for ixekizumab Q4W, 60.4% for ixekizumab Q2W, and 24.5% for placebo. Statistically greater responses compared with placebo were observed in the severe population for ACR 50, ACR 70, ACR core set, disease activity index for psoriatic arthritis (DAPSA) low disease activity and DAPSA remission, and 28-joint disease activity score using C-reactive protein, as well as Psoriasis Area and Severity Index (PASI) 75, PASI 90, and PASI 100 (p ≤ 0.001). Efficacy findings and the safety profile of ixekizumab in the severe population were consistent with those of the overall population, with no new safety concerns identified.</p><p><strong>Conclusions: </strong>In patients with severe psoriatic arthritis, 24 weeks of treatment with ixekizumab resulted in improvements in both joint and skin symptoms. The safety profile in the severe population was consistent with the established safety profile of ixekizumab.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT01695239.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49681807","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}