Rheumatology and Therapy最新文献

{"title":"Risk Stratification of Patients with Psoriatic Arthritis and Ankylosing Spondylitis for Treatment with Tofacitinib: A Review of Current Clinical Data","authors":"Lars Erik Kristensen, Atul Deodhar, Ying-Ying Leung, Ivana Vranic, Mahta Mortezavi, Lara Fallon, Arne Yndestad, Cassandra D. Kinch, Dafna D. Gladman","doi":"10.1007/s40744-024-00662-5","DOIUrl":"https://doi.org/10.1007/s40744-024-00662-5","url":null,"abstract":"<p>In this commentary, we review clinical data which helps inform individualized benefit–risk assessment for tofacitinib in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). ORAL Surveillance, a safety trial of patients ≥ 50 years of age with rheumatoid arthritis (RA) and cardiovascular risk factors, found increased rates of safety outcomes (including major adverse cardiovascular events [MACE], malignancies excluding non-melanoma skin cancer, and venous thromboembolism) with tofacitinib versus tumor necrosis factor inhibitors (TNFi). Post hoc analyses of ORAL Surveillance have identified subpopulations with different relative risk versus TNFi; higher risk with tofacitinib was confined to patients ≥ 65 years of age and/or long-time current/past smokers, and specifically for MACE, patients with a history of atherosclerotic cardiovascular disease (ASCVD). In patients without these risk factors, risk differences between tofacitinib and TNFi could not be detected. Given differences in demographics, pathophysiology, and comorbidities, we sought to examine whether the risk stratification observed in RA is also appropriate for PsA and AS. Data from the PsA tofacitinib development program show low absolute risk of safety outcomes in patients &lt; 65 years of age and never smokers, and low MACE risk in patients with no history of ASCVD, consistent with results from ORAL Surveillance. No MACE, malignancies, or venous thromboembolism were reported in the tofacitinib AS development program. The mechanism of the ORAL Surveillance safety findings is unknown, and there are no similar prospective studies of sufficient size and duration. Accordingly, it is appropriate to use a precautionary approach and extrapolate differentiating risk factors identified from ORAL Surveillance (age ≥ 65 years, long-time current/past smoking, and history of ASCVD) to PsA and AS. We recommend an individualized approach to treatment decisions based on these readily identifiable risk factors, in line with updated labeling for Janus kinase inhibitors and international guidelines for the treatment of PsA and AS.</p><p><b>Trial Registration:</b> NCT02092467, NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02281552, NCT02187055, NCT02831855, NCT00413699, NCT00661661, NCT01877668, NCT01882439, NCT01976364, NCT00678210, NCT01710046, NCT01241591, NCT01186744, NCT01276639, NCT01309737, NCT01163253, NCT01786668, NCT03502616.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":"49 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140841832","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}

{"title":"Safety Profile of Upadacitinib up to 5 Years in Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis: An Integrated Analysis of Clinical Trials","authors":"Gerd R. Burmester, Jayne Stigler, Andrea Rubbert-Roth, Yoshiya Tanaka, Valderilio F. Azevedo, Derek Coombs, Ivan Lagunes, Ralph Lippe, Peter Wung, Lianne S. Gensler","doi":"10.1007/s40744-024-00671-4","DOIUrl":"https://doi.org/10.1007/s40744-024-00671-4","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>This integrated analysis of the phase 2/3 and phase 3 SELECT trials describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, for up to 5 years of exposure across psoriatic arthritis (PsA), ankylosing spondylitis (AS), and non-radiographic axial spondyloarthritis (nr-axSpA) (including pooled axial spondyloarthritis [axSpA]).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Safety data from five trials of upadacitinib in PsA (2 trials), AS (2 trials), and nr-axSpA (1 trial) were analyzed up to a data cut-off of August 15, 2022. One PsA study included adalimumab as an active comparator. Treatment-emergent adverse events (TEAEs) were summarized for PsA (pooled upadacitinib 15 mg once daily and adalimumab 40 mg biweekly), AS (pooled upadacitinib 15 mg), nr-axSpA (upadacitinib 15 mg), and pooled axSpA (pooled upadacitinib 15 mg from axSpA trials). TEAEs were reported as exposure-adjusted event rates per 100 patient-years (E/100 PY).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 1789 patients (PsA, <i>n</i> = 907; AS, <i>n</i> = 596; nr-axSpA, <i>n</i> = 286) received ≥ 1 dose of upadacitinib 15 mg for 3689 PY of exposure or adalimumab (<i>n</i> = 429) for 1147 PY of exposure. Overall TEAEs and serious TEAEs were highest in PsA and numerically higher with upadacitinib versus adalimumab; rates were similar between AS and nr-axSpA. In PsA, higher rates of serious infection, herpes zoster (HZ), lymphopenia, and nonmelanoma skin cancer (NMSC) were observed with upadacitinib versus adalimumab. Rates of malignancy excluding NMSC, adjudicated major adverse cardiovascular events, and adjudicated venous thromboembolic events were comparable between upadacitinib and adalimumab in PsA and were similar across diseases.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Higher rates of serious infection, HZ, lymphopenia, and NMSC were observed with upadacitinib versus adalimumab in PsA; slightly elevated rates for most of these TEAEs were seen with upadacitinib in PsA versus axSpA. Upadacitinib 15 mg demonstrated a generally consistent safety profile across disease states with no new safety signals identified.</p><h3 data-test=\"abstract-sub-heading\">Trial Registration</h3><p>SELECT-AXIS 1: NCT03178487; SELECT-AXIS 2: NCT04169373; SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":"87 3 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810652","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}

{"title":"A Machine Learning Approach for Prediction of CDAI Remission with TNF Inhibitors: A Concept of Precision Medicine from the FIRST Registry","authors":"Koshiro Sonomoto, Yoshihisa Fujino, Hiroaki Tanaka, Atsushi Nagayasu, Shingo Nakayamada, Yoshiya Tanaka","doi":"10.1007/s40744-024-00668-z","DOIUrl":"https://doi.org/10.1007/s40744-024-00668-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>This study aimed to develop low-cost models using machine learning approaches predicting the achievement of Clinical Disease Activity Index (CDAI) remission 6 months after initiation of tumor necrosis factor inhibitors (TNFi) as primary biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for rheumatoid arthritis (RA).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Data of patients with RA initiating TNFi as first b/tsDMARD after unsuccessful methotrexate treatment were collected from the FIRST registry (August 2003 to October 2022). Baseline characteristics and 6-month CDAI were collected. The analysis used various machine learning approaches including logistic regression with stepwise variable selection, decision tree, support vector machine, and lasso logistic regression (Lasso), with 48 factors accessible in routine clinical practice for the prediction model. Robustness was ensured by k-fold cross validation.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Among the approaches tested, Lasso showed the advantages in predicting CDAI remission: with a mean area under the curve 0.704, sensitivity 61.7%, and specificity 69.9%. Predicted TNFi responders achieved CDAI remission at an average rate of 53.2%, while only 26.4% of predicted TNFi non-responders achieved remission. Encouragingly, the models generated relied solely on patient-reported outcomes and quantitative parameters, excluding subjective physician input.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>While external cohort validation is warranted for broader applicability, this study highlights the potential for a low-cost predictive model to predict CDAI remission following TNFi treatment. The approach of the study using only baseline data and 6-month CDAI measures, suggests the feasibility of establishing regional cohorts to generate low-cost models tailored to specific regions or institutions. This may facilitate the application of regional/in-house precision medicine strategies in RA management.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":"13 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626114","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}

{"title":"Exploring the Effects of Ixekizumab on Pain in Patients with Ankylosing Spondylitis Based on Objective Measures of Inflammation: Post Hoc Analysis from a Large Randomized Clinical Trial","authors":"Kurt de Vlam, Walter P. Maksymowych, Gaia Gallo, Proton Rahman, Philip Mease, Venkatesh Krishnan, Conor J. McVeigh, Jeffrey Lisse, Danting Zhu, Rebecca J. Bolce, Philip G. Conaghan","doi":"10.1007/s40744-024-00660-7","DOIUrl":"https://doi.org/10.1007/s40744-024-00660-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>The objective of this analysis is to evaluate the improvement in spinal pain with ixekizumab, placebo, and adalimumab based on objective measures of inflammation response in patients with ankylosing spondylitis (AS).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The COAST-V 52-week, double-blind, placebo-controlled, randomized phase III trial examined the efficacy of ixekizumab in patients with active AS; adalimumab was used as an active reference arm. Treatment effects on reduction in pain were assessed by objective measures of controlled and persisting inflammation (defined by magnetic resonance imaging [MRI], C-reactive protein [CRP], or MRI + CRP status). Pathway analysis was used to analyze treatment effect that was not attributable to reduction in inflammation biomarkers.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>In patients with AS, when inflammation was controlled as assessed by MRI, patients treated with ixekizumab experienced a reduction in spinal pain at night (SP-N, numeric rating scale, ixekizumab mean = − 3.9, <i>p</i> &lt; 0.001, adalimumab mean = − 2.6, <i>p</i> &lt; 0.05) compared to placebo (mean = − 1.6) at week 16. When inflammation was controlled as assessed by MRI + CRP, ixekizumab and adalimumab had numerically greater reductions at week 16 in SP-N versus placebo. All ixekizumab groups had further improvements at week 52. When inflammation was persisting as assessed by MRI + CRP, ixekizumab-treated patients had significant reduction in SP-N (mean = − 3.7, <i>p</i> &lt; 0.001) versus placebo (mean = − 1.7), improvement with adalimumab did not reach significance (mean = − 2.6, <i>p</i> = 0.06). In the pathway analysis at week 16, ixekizumab had a greater effect on pain outcomes compared to adalimumab.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This post hoc analysis is supportive of the hypothesis that ixekizumab reduces pain in AS by additional mechanisms other than the reduction of measurable inflammation.</p><h3 data-test=\"abstract-sub-heading\">Trial Registration Number</h3><p>NCT02696785.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":"50 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630789","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}

{"title":"Efficacy and Safety of Secukinumab in US Patients with Psoriatic Arthritis: A Subgroup Analysis of the Phase 3 FUTURE Studies","authors":"Alan J. Kivitz, Joel M. Kremer, Clarence W. Legerton, Luminita Pricop, Atul Singhal","doi":"10.1007/s40744-024-00666-1","DOIUrl":"https://doi.org/10.1007/s40744-024-00666-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>The aim of this work is to evaluate secukinumab vs. placebo in a challenging-to-treat and smaller US patient subpopulation of the international FUTURE 2–5 studies in patients with psoriatic arthritis (PsA).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Data were pooled from US patients enrolled in the phase 3 FUTURE 2–5 studies (NCT01752634, NCT01989468, NCT02294227, and NCT02404350). Patients received secukinumab 300 or 150 mg with subcutaneous loading dose, secukinumab 150 mg without subcutaneous loading dose, or placebo. Categorical efficacy and health-related quality-of-life (QoL) outcomes and safety were evaluated at week 16. Subgroup analyses were performed based on tumor necrosis factor inhibitor (TNFi) status and body mass index (BMI). For hypothesis generation, odds ratios (ORs) for American College of Rheumatology (ACR) 20/50/70 and Psoriasis Area and Severity Index (PASI) 75/90/100 responses by treatment were estimated using logistic regression without adjustment for multiple comparisons.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Of 2148 international patients originally randomized, 279 US patients were included in this pooled analysis. Mean BMI was &gt; 30 kg/m² and 55.2% had prior TNFi treatment. ORs for ACR20/50/70 significantly favored patients receiving secukinumab 300 mg and 150 mg with loading dose vs. placebo (<i>P</i> &lt; 0.05), but not those receiving secukinumab 150 mg without loading dose vs. placebo. For PASI75, ORs favored all secukinumab groups over placebo (<i>P</i> &lt; 0.05); for PASI90 and PASI100, only the secukinumab 300-mg group was significantly favored over placebo (<i>P</i> &lt; 0.05).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>In this challenging sub-population of US patients with PsA, secukinumab provided rapid improvements in disease activity and QoL. Patients with PsA and active psoriasis might benefit more from secukinumab 300 mg than 150 mg.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":"3 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140576020","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}

{"title":"Clinical Characteristics of “Severe” Peripheral Psoriatic Arthritis: A Retrospective Analysis of a Longitudinal Cohort","authors":"Ennio Lubrano, Silvia Scriffignano, Fabio Massimo Perrotta","doi":"10.1007/s40744-024-00667-0","DOIUrl":"https://doi.org/10.1007/s40744-024-00667-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>The concept of severity in a multidomain disease such as psoriatic arthritis (PsA) is still not well defined. The aim of this study was to identify the clinical characteristics of patients with severe peripheral PsA.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Retrospective analysis of a longitudinal cohort. Demographic and clinical characteristics of patients with PsA were collected at baseline and at last follow-up. We defined the severe population using the modified Composite Psoriatic Disease Activity Index (mCPDAI); which excludes ankylosing spondylitis quality of life scale). Hence, patients with a score of 3 in at least one domain were defined as having severe PsA. Clinical characteristics of patients fulfilling the definition of severe PsA were compared to those non-severe.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p> We evaluated 177 patients with peripheral PsA (M/F: 98/76). Of these, 64 (36.1%) were identified as severe according to the mCPDAI criteria, at baseline. Eighteen patients (10.1%) at last follow-up still met the definition of severe PsA. At last follow-up visit, severe patients with PsA were only males (18/18, <i>P</i> &lt; 0.01) and have worse outcomes in terms of disease activity, pain, function, and impact of disease. Male sex and the severity of skin involvement at baseline were factors associated with the presence of severe PsA. The agreement between the presence of severe PsA and the absence of minimal disease activity was slight [Cohen’s <i>k</i>: 0.174 (0.084–0.264)].</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Our study showed that severe patients with PsA had more disease activity, pain, and impact of disease than non-severe patients. Furthermore, we demonstrated that severity and disease activity are not interchangeable concepts.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":"61 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140575753","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}

{"title":"Current Use and Barriers to Point-of-Care Ultrasound in Rheumatology: A National Survey of VA Medical Centers","authors":"","doi":"10.1007/s40744-024-00665-2","DOIUrl":"https://doi.org/10.1007/s40744-024-00665-2","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Introduction</h3> <p>Point-of-care ultrasound (POCUS) can assist rheumatologists in monitoring disease activity, establishing diagnoses, and guiding procedural interventions. POCUS use has been increasing, but little is known about current use and barriers among rheumatologists. The purpose of this study was to characterize current POCUS use, training needs, and barriers to use among rheumatologists in practice.</p> </span> <span> <h3>Methods</h3> <p>A prospective observational study of all Veterans Affairs (VA) medical centers was conducted using a web-based survey sent to all chiefs of staff and rheumatology chiefs about current POCUS use, training needs, barriers, and policies.</p> </span> <span> <h3>Results</h3> <p>All chiefs of staff (<em>n</em> = 130) and rheumatology chiefs at VA medical centers (<em>n</em> = 95) were surveyed with 100% and 84% response rates, respectively. The most common diagnostic POCUS applications were evaluation of synovitis, joint effusion, tendinopathies, bursitis, and rotator cuff. The most common procedural applications were arthrocentesis and joint, bursa, and tendon injection. Most rheumatology chiefs (69%) expressed interest in training for their group. The most common barriers to POCUS use were lack of trained providers (68%), funding for training (54%), training opportunities (38%), funding for travel (38%), and ultrasound equipment (31%). Lack of POCUS infrastructure was common, and few facilities had POCUS policies (20%), image archiving (25%), or quality assurance processes (6%).</p> </span> <span> <h3>Conclusion</h3> <p>Currently, half of rheumatology groups use diagnostic and procedural ultrasound applications. Most rheumatology groups desire training, and lack of training and equipment were the most common barriers to ultrasound use. Deliberate investment is needed in ultrasound training and infrastructure for systematic adoption of POCUS in rheumatology.</p> <p>Graphical Abstract available for this article.</p> </span> <span> <h3>Trial Registration</h3> <p>NCT03296280.</p> </span> <span> <h3>Graphical Abstract</h3> <p><span> <span> <img alt=\"\" src=\"https://static-content.springer.com/image/MediaObjects/40744_2024_665_Figa_HTML.png\"/> </span> </span></p> </span>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":"13 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140576013","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}

{"title":"Effectiveness of Tofacitinib in Patients Initiating Therapy for Psoriatic Arthritis: Results from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.","authors":"Philip J Mease, Pamela Young, Lara Fallon, Rajiv Mundayat, Oluwaseyi Dina, Taylor Blachley, Nicole Middaugh, Alexis Ogdie","doi":"10.1007/s40744-023-00631-4","DOIUrl":"10.1007/s40744-023-00631-4","url":null,"abstract":"<p><strong>Introduction: </strong>Randomized controlled trials have demonstrated tofacitinib efficacy for psoriatic arthritis (PsA); however, real-world effectiveness data are limited. This real-world analysis assessed baseline demographics/disease characteristics and tofacitinib effectiveness in patients with PsA in the CorEvitas PsA/Spondyloarthritis Registry.</p><p><strong>Methods: </strong>This study (NCT05195814) included patients with PsA initiating tofacitinib from December 2017-December 2021, as monotherapy or with oral small molecules (methotrexate/leflunomide/sulfasalazine/apremilast), pre-existing use, or initiated concurrently.</p><p><strong>Outcomes: </strong>mean change from baseline in disease activity/patient-reported outcomes, proportion of patients achieving low disease activity (LDA)/remission at 6 ± 3 months, and discontinuation rates.</p><p><strong>Results: </strong>Of 222 patients with PsA who initiated tofacitinib (60.8% as monotherapy), 123 patients had 6 ± 3 months of follow-up. At initiation, 59.7% were female, 92.3% were White, mean age was 56.3 years, PsA duration since diagnosis was 8.2 years, and 25.7% were biologic disease-modifying antirheumatic drug (bDMARD)-naïve. Improvements to 6 ± 3 months were observed with tofacitinib for Clinical Disease Activity Index for PsA (cDAPSA), DAPSA, PsA Disease Activity Score (PASDAS), Clinical Disease Activity Index, body surface area (BSA), tender/swollen joint count, patient fatigue, pain, Patient Global Skin Assessment, and Health Assessment Questionnaire-Disability Index. At 6 ± 3 months, 25.0%/7.8% of patients treated with tofacitinib achieved cDAPSA-defined LDA/remission, 18.2% achieved minimal disease activity, 30.8% had PASDAS ≤ 3.2, 42.9%/29.4% had resolved enthesitis/dactylitis, and 22.5% achieved BSA = 0%. Tofacitinib discontinuation occurred in 51.2% of patients (51.6% of monotherapy initiators) at/prior to 6 ± 3 months (27.6%/23.6%), 57.1% of whom switched to tumor necrosis factor/interleukin-17 inhibitors. Reasons for discontinuation were not reported in 85.3%/79.3% of patients who discontinued at/prior to 6 ± 3 months.</p><p><strong>Conclusions: </strong>This real-world US cohort analysis described patients with PsA newly initiating tofacitinib; most were bDMARD-experienced or receiving monotherapy treatment. In patients who remained on therapy (48.8%), tofacitinib was effective across multiple PsA domains at 6 ± 3 months. Limitations included small patient numbers at follow-up and potential selection bias.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT05195814.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"313-329"},"PeriodicalIF":3.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10920500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513573","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 Impact of Systemic Lupus Erythematosus Flares on Clinical and Economic Outcomes: The CHAMOMILE Claims Database Study in Germany.","authors":"Bo Ding, Marc Pignot, Elena Garal-Pantaler, Beate Villinger, Sebastian Schefzyk, Barnabas Desta, Heide A Stirnadel-Farrant, Andreas Schwarting","doi":"10.1007/s40744-023-00635-0","DOIUrl":"10.1007/s40744-023-00635-0","url":null,"abstract":"<p><strong>Introduction: </strong>CHAMOMILE (CHaracteristics and impact of flares on clinicAl and econoMic OutcoMes In patients with systemic Lupus Erythematosus [SLE]) examined how flares in the year of SLE diagnosis impact future disease activity and damage, productivity, healthcare resource utilization (HCRU), and costs in patients with SLE in Germany.</p><p><strong>Methods: </strong>CHAMOMILE was a retrospective cohort study of adults with an SLE diagnosis in the German Sickness Fund Database from 1 July 2010 to 31 December 2013. Patients were classified according to their greatest flare severity during the baseline year (none, mild, or moderate/severe). The number and severity of flares were assessed annually over 5-8.5 follow-up years, along with SLE organ/system damage, treatments, work disability, and HCRU metrics.</p><p><strong>Results: </strong>Of 2088 patients (84.6% female; mean age [standard deviation] 51.4 [16.1] years; mean follow-up 6.8 [2.1] years), 34.3% (n = 716) were flare-free, 29.8% (n = 622) had mild flares, and 35.9% (n = 750) had moderate/severe flares at baseline. Baseline flare severity was related to future flares: rates during follow-up were higher in patients with moderate/severe baseline flares compared with those with mild or no baseline flares (89.6 vs 78.5 and 44.2 flares/100 patient years, respectively). Overall, 80.2% (n = 1675) of patients received glucocorticoids at least once during baseline and follow-up. Patients' HCRU was generally greatest in their baseline year. Costs were highest in patients with moderate/severe baseline flares.</p><p><strong>Conclusion: </strong>Baseline flare severity provided insight into a patient's disease course and the clinical and economic burden of SLE over time, highlighting the ramifications of uncontrolled disease for patients with SLE.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"285-299"},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10920501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513575","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":"Real-World Use and Effectiveness Outcomes in Patients with Rheumatoid Arthritis Treated with Upadacitinib: An Analysis from the CorEvitas Registry.","authors":"Joshua F Baker, Patrick Zueger, Mira Ali, Denise Bennett, Miao Yu, Yolanda Munoz Maldonado, Robert R McLean","doi":"10.1007/s40744-024-00639-4","DOIUrl":"10.1007/s40744-024-00639-4","url":null,"abstract":"<p><strong>Introduction: </strong>Data assessing longer-term real-world effectiveness and treatment patterns with upadacitinib (UPA), a Janus kinase inhibitor, in rheumatoid arthritis (RA) are lacking. We assessed improvement in clinical and patient-reported outcomes and treatment patterns for up to 12 months among adult patients with RA initiating UPA.</p><p><strong>Methods: </strong>Data were collected from the CorEvitas^® RA Registry (08/2019-04/2022). Eligible patients had moderate to severe RA (Clinical Disease Activity Index [CDAI] > 10) and follow-up visits at 6 or 12 months after UPA initiation. Outcomes were mean change from baseline, percentage achieving minimal clinically important differences (MCID) in clinical and patient-reported outcomes, and disease activity at follow-up. We evaluated clinical outcomes and therapy changes among patients with tumor necrosis factor inhibitor (TNFi) experience and among those receiving UPA as first-line therapy, as well as those receiving UPA as monotherapy versus as part of combination therapy. We further evaluated whether outcomes were similar among those that remained on therapy.</p><p><strong>Results: </strong>Patients treated with UPA (6-month cohort, N = 469; 12-month cohort, N = 263) had statistically significant improvements (p < 0.001) in mean CDAI, tender/swollen joint counts, pain, and fatigue at follow-up. At 12 months, 46.0% achieved MCID in CDAI and 40.0% achieved low disease activity/remission. Overall, 43.0% discontinued UPA at 12 months; of those receiving combination treatment (N = 90) with conventional therapies and UPA, 42.2% (N = 38) discontinued conventional therapy. Findings were similar in the 6-month cohort and among subgroups. Changes from baseline and proportions of patients achieving MCID or clinical outcomes tended to be numerically lower among patients with TNFi experience and numerically higher among those receiving UPA as first-line therapy.</p><p><strong>Conclusions: </strong>UPA initiation was associated with improvements in clinical and patient-reported outcomes, with meaningful clinical improvements regardless of prior TNFi experience, line of therapy, or concomitant use of conventional therapies. Further research is needed to better understand sustained response of UPA over longer treatment periods.</p>","PeriodicalId":21267,"journal":{"name":"Rheumatology and Therapy","volume":" ","pages":"363-380"},"PeriodicalIF":3.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10920593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723902","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}