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P J Mease - One of the best experts on this subject based on the ideXlab platform.
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Characterization of Patients With Axial Spondyloarthritis by Enthesitis Presence: Data from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry
ACR open rheumatology, 2020Co-Authors: P J Mease, Sabrina Rebello, Robert Mclean, Yujin Park, Mei Liu, Winnie Hua, Alexis OgdieAbstract:OBJECTIVE To compare the characteristics of patients with axial spondyloarthritis (axSpA) who had Enthesitis versus those without Enthesitis. METHODS This study included adult patients with axSpA enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry (March 2013 to August 2018). Enthesitis was assessed at enrollment via the Spondyloarthritis Research Consortium of Canada Enthesitis Index. Characteristics were compared between patients with and without Enthesitis using t tests or Wilcoxon rank-sum tests for continuous variables and χ2 or Fisher exact tests for categorical variables. RESULTS Of 477 patients with axSpA, 121 (25.4%) had Enthesitis (mean, 3.9 sites) at enrollment. Higher proportions of patients with Enthesitis were female and had nonradiographic axSpA than those without Enthesitis (both P < 0.05). Additionally, higher proportions of patients with Enthesitis had prior biologic (38.8% vs 27.2%) and conventional synthetic disease-modifying antirheumatic drug (csDMARD; 24.8% vs 13.3%) use and were currently receiving a combination of biologics and csDMARDs (28.6% vs 18.1%) than those without Enthesitis. Patients with Enthesitis had worse disease activity (tender and swollen joint counts, physician global assessment, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondylitis Functional Index), spinal mobility, and quality of life (pain, fatigue, Health Assessment Questionnaire, and EuroQol visual analog scale scores); greater work impairment; and had a history of depression and fibromyalgia than those without Enthesitis (all P < 0.05). CONCLUSION In this US-based real-world study, Enthesitis in patients with axSpA was associated with worse disease activity and quality of life than those with no Enthesitis.
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characterization of patients with axial spondyloarthritis by Enthesitis presence data from the corrona psoriatic arthritis spondyloarthritis registry
ACR open rheumatology, 2020Co-Authors: P J Mease, Sabrina Rebello, Robert Mclean, Esther Yi, Yujin Park, Alexis OgdieAbstract:OBJECTIVE To compare the characteristics of patients with axial spondyloarthritis (axSpA) who had Enthesitis versus those without Enthesitis. METHODS This study included adult patients with axSpA enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry (March 2013 to August 2018). Enthesitis was assessed at enrollment via the Spondyloarthritis Research Consortium of Canada Enthesitis Index. Characteristics were compared between patients with and without Enthesitis using t tests or Wilcoxon rank-sum tests for continuous variables and χ2 or Fisher exact tests for categorical variables. RESULTS Of 477 patients with axSpA, 121 (25.4%) had Enthesitis (mean, 3.9 sites) at enrollment. Higher proportions of patients with Enthesitis were female and had nonradiographic axSpA than those without Enthesitis (both P < 0.05). Additionally, higher proportions of patients with Enthesitis had prior biologic (38.8% vs 27.2%) and conventional synthetic disease-modifying antirheumatic drug (csDMARD; 24.8% vs 13.3%) use and were currently receiving a combination of biologics and csDMARDs (28.6% vs 18.1%) than those without Enthesitis. Patients with Enthesitis had worse disease activity (tender and swollen joint counts, physician global assessment, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondylitis Functional Index), spinal mobility, and quality of life (pain, fatigue, Health Assessment Questionnaire, and EuroQol visual analog scale scores); greater work impairment; and had a history of depression and fibromyalgia than those without Enthesitis (all P < 0.05). CONCLUSION In this US-based real-world study, Enthesitis in patients with axSpA was associated with worse disease activity and quality of life than those with no Enthesitis.
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impact of guselkumab an interleukin 23 p19 subunit inhibitor on Enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis results from a randomised placebo controlled phase ii study
RMD Open, 2020Co-Authors: P J Mease, Dennis Mcgonagle, Dafna D Gladman, Atul Deodhar, Peter Nash, Wolfhenning Boehncke, Alice B Gottlieb, Elizabeth C Hsia, Chetan KaryekarAbstract:Objective To evaluate the effect of guselkumab on Enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA). Methods This was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0–3 on each digit; Enthesitis was assessed using the Leeds Enthesitis Index (0–6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses. Results Of 149 randomised patients, 107 patients had Enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in Enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of Enthesitis and dactylitis. At week 56, mean improvements in Enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in Enthesitis and dactylitis versus non-responders (week 24). Conclusions At week 24, the guselkumab group had greater mean improvements in Enthesitis and dactylitis and greater proportions of patients with resolution of Enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in Enthesitis and dactylitis. Trial registration number ClinicalTrials.gov: NCT02319759. URL: https://clinicaltrials.gov/ct2/show/NCT02319759; Registered 18 December 2014.
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Impact of guselkumab, an interleukin-23 p19 subunit inhibitor, on Enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis: results from a randomised, placebo-controlled, phase II study
'BMJ', 2020Co-Authors: P J Mease, Dd Gladman, Deodhar A, Dg Mcgonagle, Nash P, Boehncke W-h, Gottlieb A, Xu S, Ec HsiaAbstract:Objective To evaluate the effect of guselkumab on Enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA). Methods This was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0–3 on each digit; Enthesitis was assessed using the Leeds Enthesitis Index (0–6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses. Results Of 149 randomised patients, 107 patients had Enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in Enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of Enthesitis and dactylitis. At week 56, mean improvements in Enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in Enthesitis and dactylitis versus non-responders (week 24). Conclusions At week 24, the guselkumab group had greater mean improvements in Enthesitis and dactylitis and greater proportions of patients with resolution of Enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in Enthesitis and dactylitis
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Secukinumab efficacy on resolution of Enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies
Arthritis research & therapy, 2019Co-Authors: Laura C. Coates, Dennis Mcgonagle, Georg Schett, P J Mease, Iain B Mcinnes, Johan K Wallman, Lawrence Rasouliyan, Erhard Quebe-fehling, D L Asquith, Andreas E R FasthAbstract:BACKGROUND: Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with Enthesitis are associated with worse outcomes than those without Enthesitis. The effect of secukinumab on the resolution of Enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. METHOD: Assessments of Enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of Enthesitis count (EC = 0), median time to first resolution of Enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3-6) to full resolution (FR), stable (similar or reduction of EC), or worse (EC > baseline). Efficacy outcomes (ACR, PASI, HAQ-DI, SF-36 PCS, and DAS28-CRP) were assessed in patients with or without baseline Enthesitis. Results are reported for secukinumab 300 and 150 mg in the overall population and by prior TNFi treatment. RESULTS: A total of 65% (466/712) of patients had baseline Enthesitis. In the overall population, FR was achieved as early as week 16 in 65% (300 mg) and 56% (150 mg) versus 44% (placebo) patients, with further improvements to 91% (300 mg) and 88% (150 mg) at week 104. The majority (89%) of patients without Enthesitis at baseline maintained this status at week 104. Median days to resolution of EC were shorter with secukinumab 300 and 150 mg versus placebo (57 and 85 vs 167 days, respectively). In patients with EC of 1 or 2, shift analysis from baseline to week 24 showed that more patients achieved FR with secukinumab 300 mg and 150 mg versus placebo, whereas no difference between secukinumab and placebo was shown in the more severe patients with EC of 3-6. Increases in proportions of patients with FR were observed with secukinumab irrespective of the severity of EC from baseline to week 104. Improvements in efficacy outcomes were similar in patients with or without Enthesitis treated with secukinumab 300 mg. CONCLUSION: Secukinumab provided early and sustained resolution of Enthesitis in patients with PsA over 2 years. Secukinumab 300 mg provided higher resolution than 150 mg in patients with more severe baseline EC and showed similar overall efficacy in patients with or without Enthesitis. TRIAL REGISTRATION: FUTURE 2: ClinicalTrials.gov, NCT01752634 (date of study registration: December 19, 2012), and EudraCT, 2012-004439-22 (date of study registration: December 12, 2012) FUTURE 3: ClinicalTrials.gov, NCT01989468 (date of study registration: November 21, 2013), and EudraCT, 2013-004002-25 (date of study registration: December 17, 2013).
Dennis Mcgonagle - One of the best experts on this subject based on the ideXlab platform.
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impact of guselkumab an interleukin 23 p19 subunit inhibitor on Enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis results from a randomised placebo controlled phase ii study
RMD Open, 2020Co-Authors: P J Mease, Dennis Mcgonagle, Dafna D Gladman, Atul Deodhar, Peter Nash, Wolfhenning Boehncke, Alice B Gottlieb, Elizabeth C Hsia, Chetan KaryekarAbstract:Objective To evaluate the effect of guselkumab on Enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA). Methods This was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0–3 on each digit; Enthesitis was assessed using the Leeds Enthesitis Index (0–6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses. Results Of 149 randomised patients, 107 patients had Enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in Enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of Enthesitis and dactylitis. At week 56, mean improvements in Enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in Enthesitis and dactylitis versus non-responders (week 24). Conclusions At week 24, the guselkumab group had greater mean improvements in Enthesitis and dactylitis and greater proportions of patients with resolution of Enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in Enthesitis and dactylitis. Trial registration number ClinicalTrials.gov: NCT02319759. URL: https://clinicaltrials.gov/ct2/show/NCT02319759; Registered 18 December 2014.
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Secukinumab efficacy on resolution of Enthesitis in psoriatic arthritis: pooled analysis of two phase 3 studies
Arthritis research & therapy, 2019Co-Authors: Laura C. Coates, Dennis Mcgonagle, Georg Schett, P J Mease, Iain B Mcinnes, Johan K Wallman, Lawrence Rasouliyan, Erhard Quebe-fehling, D L Asquith, Andreas E R FasthAbstract:BACKGROUND: Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with Enthesitis are associated with worse outcomes than those without Enthesitis. The effect of secukinumab on the resolution of Enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. METHOD: Assessments of Enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of Enthesitis count (EC = 0), median time to first resolution of Enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3-6) to full resolution (FR), stable (similar or reduction of EC), or worse (EC > baseline). Efficacy outcomes (ACR, PASI, HAQ-DI, SF-36 PCS, and DAS28-CRP) were assessed in patients with or without baseline Enthesitis. Results are reported for secukinumab 300 and 150 mg in the overall population and by prior TNFi treatment. RESULTS: A total of 65% (466/712) of patients had baseline Enthesitis. In the overall population, FR was achieved as early as week 16 in 65% (300 mg) and 56% (150 mg) versus 44% (placebo) patients, with further improvements to 91% (300 mg) and 88% (150 mg) at week 104. The majority (89%) of patients without Enthesitis at baseline maintained this status at week 104. Median days to resolution of EC were shorter with secukinumab 300 and 150 mg versus placebo (57 and 85 vs 167 days, respectively). In patients with EC of 1 or 2, shift analysis from baseline to week 24 showed that more patients achieved FR with secukinumab 300 mg and 150 mg versus placebo, whereas no difference between secukinumab and placebo was shown in the more severe patients with EC of 3-6. Increases in proportions of patients with FR were observed with secukinumab irrespective of the severity of EC from baseline to week 104. Improvements in efficacy outcomes were similar in patients with or without Enthesitis treated with secukinumab 300 mg. CONCLUSION: Secukinumab provided early and sustained resolution of Enthesitis in patients with PsA over 2 years. Secukinumab 300 mg provided higher resolution than 150 mg in patients with more severe baseline EC and showed similar overall efficacy in patients with or without Enthesitis. TRIAL REGISTRATION: FUTURE 2: ClinicalTrials.gov, NCT01752634 (date of study registration: December 19, 2012), and EudraCT, 2012-004439-22 (date of study registration: December 12, 2012) FUTURE 3: ClinicalTrials.gov, NCT01989468 (date of study registration: November 21, 2013), and EudraCT, 2013-004002-25 (date of study registration: December 17, 2013).
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Enthesitis: Much More Than Focal Insertion Point Inflammation
Current rheumatology reports, 2018Co-Authors: Abdulla Watad, Richard Cuthbert, Howard Amital, Dennis McgonagleAbstract:Recognition of the importance of Enthesitis as the pivotal pathological process underpinning spondyloarthropathies (SpA) has increased in recent years. Thus, we summarized the current knowledge on the pathogenic role of Enthesitis on SpA shown by both animal models and human studies in vivo. Experimental models have shown several SpA-like diseases that commence at entheses and are linked to nail disease as well as dactylitis, two important entheseal-associated conditions in humans. Frequently, Enthesitis is not the primary outcome measure in studies of peripheral PsA and SpA although arguably it is the key parameter being indirectly assessed in spinal disease in ankylosing spondylitis. The use of different agents including JAK, IL-17, and IL-23 inhibitors contributes significantly to our understanding of Enthesitis in terms of involved immune pathways. Enthesitis and enthesis organ inflammation may be the primary pathological process underlying SpA associated skeletal inflammation. Emergent studies are beginning to elucidate the molecular basis for this type of joint inflammatory response.
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Enthesitis: from pathophysiology to treatment
Nature Reviews Rheumatology, 2017Co-Authors: Georg Schett, Bruce Kirkham, Dirk Elewaut, Maria-antonietta D'agostino, Rik J. Lories, Enrique R. Soriano, Dennis McgonagleAbstract:Entheses are the insertion sites of tendons and ligaments to the bone surface and are essential structures for locomotion. Inflammation of the entheses (Enthesitis) is a key feature of psoriatic arthritis and spondyloarthritis. To date, our conceptual understanding of Enthesitis remains limited. This Review provides an insight into the pathophysiology of Enthesitis, addressing the role of biomechanics, prostaglandin E2-mediated vasodilation and the activation of innate immune cells in the initiation phase of Enthesitis, as well as the role of entheseal IL-23-responsive cells that augment inflammation by producing pro-inflammatory mediators such as IL-17A, IL-22 and TNF. In addition, the molecular steps that translate inflammation into resident tissue responses, resulting in new bone formation, are discussed. The second part of the article summarizes the clinical features of Enthesitis, and the role of clinical and imaging instruments in detecting Enthesitis are discussed together with their challenges and limitations. Finally, the Review summarizes the current treatment possibilities for Enthesitis based on the aforementioned pathophysiological concepts, focusing on the role of cytokine-blocking agents. Entheses are predominantly extra-articularly localized structures that represent a key target of musculoskeletal inflammation in diseases such as psoriatic arthritis (PsA) and spondyloarthritis (SpA) Entheses contain a specific immune microenvironment, which is activated by a combination of factors that include mechanical stress, genetic susceptibility and microbial-triggered immune activation Enthesitis arises from robust activation of prostaglandin E2 and the IL-23–IL-17 axis, leading to the influx of innate immune cells and homing of inflammation into the entheses, which is followed by mesenchymal tissue responses and new bone formation Clinical and imaging instruments have been developed that enable the reliable detection and monitoring of Enthesitis in patients with PsA and SpA Inhibition of the key effector cytokines of Enthesitis — IL-17, IL-23 and TNF — has shown to be effective in supporting the resolution of Enthesitis in PsA and SpA This article provides an overview of the pathophysiology of Enthesitis, from induction and inflammation to tissue proliferation and bone formation. Building on these pathophysiological concepts, the clinical presentation, assessment and treatment of Enthesitis are also discussed.
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Enthesitis: from pathophysiology to treatment
Nature reviews. Rheumatology, 2017Co-Authors: Georg Schett, Bruce Kirkham, Rik Lories, Dirk Elewaut, Maria-antonietta D'agostino, Enrique R. Soriano, Dennis McgonagleAbstract:Entheses are the insertion sites of tendons and ligaments to the bone surface and are essential structures for locomotion. Inflammation of the entheses (Enthesitis) is a key feature of psoriatic arthritis and spondyloarthritis. To date, our conceptual understanding of Enthesitis remains limited. This Review provides an insight into the pathophysiology of Enthesitis, addressing the role of biomechanics, prostaglandin E2-mediated vasodilation and the activation of innate immune cells in the initiation phase of Enthesitis, as well as the role of entheseal IL-23-responsive cells that augment inflammation by producing pro-inflammatory mediators such as IL-17A, IL-22 and TNF. In addition, the molecular steps that translate inflammation into resident tissue responses, resulting in new bone formation, are discussed. The second part of the article summarizes the clinical features of Enthesitis, and the role of clinical and imaging instruments in detecting Enthesitis are discussed together with their challenges and limitations. Finally, the Review summarizes the current treatment possibilities for Enthesitis based on the aforementioned pathophysiological concepts, focusing on the role of cytokine-blocking agents.
Lihi Eder - One of the best experts on this subject based on the ideXlab platform.
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The management of Enthesitis in clinical practice.
Current opinion in rheumatology, 2020Co-Authors: Sahil Koppikar, Lihi EderAbstract:Purpose of review Enthesitis is a hallmark feature of the spondyloarthropathies (SpA). This review provides an overview of recent insights on diagnosis and management of Enthesitis. Recent findings Recent studies support the use of imaging for diagnosis because of its higher sensitivity and specificity compared with clinical examination. Several new MRI and ultrasound scoring systems have been developed for Enthesitis, which may facilitate the use of imaging in research. Enthesitis has been evaluated as a primary study outcome mainly in psoriatic arthritis (PsA); however, the use of different indices and definitions of improvement limits comparison across studies. There is very limited information about the efficacy of synthetic disease modifying antirheumatic drugs (DMARDs) for the treatment of Enthesitis. In contrast, targeted and biologic DMARDs have all shown efficacy in treating Enthesitis compared with placebo. There have been only a few head-to-head trials that compared two different cytokine inhibitors for the treatment of Enthesitis. Preliminary data suggest that targeting IL-17 or IL12/23 may be more efficacious for controlling Enthesitis than TNF inhibition. Summary Emerging data suggest interleukin-17 and 12/23 inhibitors may be the first choice in PsA patients with Enthesitis. Further head-to-head studies are needed before making definitive recommendations.
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Development and Validation of a Sonographic Enthesitis Instrument in Psoriatic Arthritis: The GRAPPA Diagnostic Ultrasound Enthesitis Tool (DUET) Project
The Journal of rheumatology. Supplement, 2020Co-Authors: Lihi Eder, Gurjit S. Kaeley, Sibel Zehra AydinAbstract:Enthesitis is a key feature in psoriatic arthritis (PsA) and may be the initial site of musculoskeletal inflammation in patients with PsA. Ultrasound (US) optimizes the detection of Enthesitis, but the lack of a validated sonographic Enthesitis scoring system for PsA limits the ability to conduct US-based studies of approaches to improve the early diagnosis of PsA. Creating a sonographic Enthesitis scoring system that reliably identifies PsA at early stages is an important step in optimizing early diagnosis and encouraging timely interventions that will ultimately improve longterm outcomes for patients with PsA. The Group for Research and Assessment of Psoriasis and PsA (GRAPPA) US working group has set a goal of improving the evaluation of Enthesitis in patients with PsA by using US through the development of a Diagnostic Ultrasound Enthesitis Tool (DUET). This article summarizes the proposed DUET study design and methodology as discussed during the 2019 GRAPPA annual meeting in Paris, France.
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The GRAPPA Sonographic Enthesitis Workshop.
The Journal of rheumatology. Supplement, 2019Co-Authors: Lihi Eder, Gurjit S. Kaeley, Sibel Zehra AydinAbstract:Enthesitis is a key feature in psoriatic arthritis (PsA) and may be the initial site of musculoskeletal inflammation in patients with PsA. Ultrasound (US) could improve the accuracy of clinical Enthesitis assessment, but at present no consensus exists on a global sonographic Enthesitis scoring method that can evaluate the extent of Enthesitis at the patient level. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) US Working Group has set up a goal to optimize the evaluation of Enthesitis in patients with PsA using US through the development and validation of new instruments using a combined data-driven and expert opinion-driven approach. This article summarizes the GRAPPA US Working Group's recent activities and focuses on a 2-day workshop that the group held following the annual 2018 GRAPPA meeting in Toronto, Ontario, Canada.
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Psoriatic Arthritis Sonographic Enthesitis Instruments: A Systematic Review of the Literature
The Journal of rheumatology, 2018Co-Authors: Ofir Elalouf, Gurjit S. Kaeley, Sibel Zehra Aydin, Sibel Bakirci Ureyen, Zahi Touma, Melanie Anderson, Lihi EderAbstract:Objective. As part of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound working group, we performed a systematic review of the literature to assess the evidence and knowledge gaps in scoring instruments of Enthesitis in psoriatic arthritis (PsA). Methods. A systematic search of PubMed, EMBase, and Cochrane databases was performed. The search strategy was constructed to find original publications containing terms related to ultrasound, Enthesitis, spondyloarthritis (SpA) or PsA. Data extraction focused on the properties of the sonographic Enthesitis instruments used in each study following components of the Outcome Measures in Rheumatology (OMERACT) filter: feasibility, test-retest reliability, construct validity as related to clinical assessment of Enthesitis, biomarkers of inflammation and imaging of Enthesitis by other modalities, discriminative validity, and responsiveness to treatment. Results. Fifty-one of 310 identified manuscripts were included. Only 1 scoring instrument of Enthesitis was specifically developed and validated in patients with PsA. Only 18 (35%) of the studies involved patients with PsA, while the remaining studies focused on SpA. In PsA, construct validity was assessed using biomarkers and clinical examination in 1 (2%) and 11 (21.5%) of the studies, respectively, whereas no studies used imaging for the same purpose. Only 2 (4%) of the studies assessed discriminative validity in PsA. Responsiveness to treatment was assessed in 7 studies, none of which included patients with PsA. Conclusion. Although sonographic Enthesitis scoring instruments have been developed for SpA, only a few have been validated in PsA. None of them passed the OMERACT filter in patients with PsA. Additional research is required before endorsing a specific instrument for the assessment of Enthesitis in patients with PsA.
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The Association Between HLA Genetic Susceptibility Markers and Sonographic Enthesitis in Psoriatic Arthritis.
Arthritis & rheumatology (Hoboken N.J.), 2018Co-Authors: Ari Polachek, Dafna D Gladman, Vinod Chandran, Richard J. Cook, Fatima Abji, Lihi EderAbstract:Objective Enthesitis is an important pathophysiologic component of psoriatic arthritis (PsA). HLA genes are implicated in the pathogenesis of PsA. Little is known about the relationship between HLA genetic susceptibility markers and Enthesitis in PsA patients. Our aim was to examine the association between HLA genetic susceptibility markers and sonographic Enthesitis in PsA. Methods A cross-sectional analysis was conducted in patients with PsA. Sonographic Enthesitis was assessed according to the Madrid Sonography Enthesitis Index scoring system. HLA genotyping was performed using sequence-specific oligonucleotide probes. The association between 6 HLA susceptibility markers of PsA and the severity of sonographic Enthesitis was assessed using multivariate regression models adjusted for age, sex, body mass index, and disease duration. Results Two hundred twenty-five patients were included, 57.8% of whom were men. The mean ± SD age was 56.1 ± 12.7 years, and the mean ± SD PsA duration was 16.9 ± 12.3 years. In the multivariate regression model, HLA-B*27 was associated with a higher Enthesitis score (β = 4.24 [95% confidence interval {95% CI} 0.02, 8.46]), and the interaction between HLA-B*27 and PsA duration was statistically significant, showing an increasing effect of HLA-B*27 with longer PsA duration (β = 4.62 [95% CI 1.38, 7.86]). Conclusion HLA-B*27 is associated with more severe sonographic Enthesitis in PsA, particularly in patients with longer disease duration. This finding highlights the possible role of genetic variants in predisposing to PsA subphenotypes.
Maria-antonietta D'agostino - One of the best experts on this subject based on the ideXlab platform.
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Clinical peripheral Enthesitis in the DESIR prospective longitudinal axial spondyloarthritis cohort.
Clinical and experimental rheumatology, 2018Co-Authors: V Nadon, A Molto, A Etcheto, Louis Bessette, Laetitia Michou, Pascal Claudepierre, D Wendling, Maria-antonietta D'agostino, Paul Haraoui, M DougadosAbstract:Objectives We aimed to describe the prevalence and characteristics of peripheral Enthesitis in recent onset axial spondyloarthritis, estimate the incidence of peripheral Enthesitis over time, and determine the factors associated with the presence of peripheral Enthesitis. Methods 708 patients with recent onset axial spondyloarthritis were enrolled in the DESIR cohort ( prospective multi-centre, longitudinal). Data regarding the patients and spondyloarthritis characteristics at baseline with a specific focus on Enthesitis and occurrence of peripheral Enthesitis were collected during the five years of follow-up. Results At inclusion, 395 patients (55.8%) reported peripheral Enthesitis. The locations were mainly the plantar fascia (53.7%) and the Achilles tendon (38.5%). During the 5-year follow-up period, 109 additional patients developed peripheral Enthesitis resulting in an estimated (Kaplan-Meier method) percentage of 71% (95% CI: 68-75). Variables associated with peripheral Enthesitis in the univariate analysis were: older age, male gender, absence of HLA B27, MRI sacroiliitis and fulfilled Modified NY criteria, presence of anterior chest wall pain, peripheral arthritis, dactylitis, psoriasis, high BASDAI, BASFI, mean score ASAS-and the use of NSAIDs. Only the history of anterior chest wall pain and of peripheral arthritis were retained in the multivariate analysis (odds ratio (OR)=1.6 [95% confidence interval [1.1-2.3], and OR=2.1 [1.4-3.0], respectively). Conclusions This study highlights the high prevalence of peripheral Enthesitis in recent onset axial spondyloarthritis, and suggests that in combination with peripheral arthritis, Enthesitis might have an impact on the burden of the disease.
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Enthesitis: from pathophysiology to treatment
Nature Reviews Rheumatology, 2017Co-Authors: Georg Schett, Bruce Kirkham, Dirk Elewaut, Maria-antonietta D'agostino, Rik J. Lories, Enrique R. Soriano, Dennis McgonagleAbstract:Entheses are the insertion sites of tendons and ligaments to the bone surface and are essential structures for locomotion. Inflammation of the entheses (Enthesitis) is a key feature of psoriatic arthritis and spondyloarthritis. To date, our conceptual understanding of Enthesitis remains limited. This Review provides an insight into the pathophysiology of Enthesitis, addressing the role of biomechanics, prostaglandin E2-mediated vasodilation and the activation of innate immune cells in the initiation phase of Enthesitis, as well as the role of entheseal IL-23-responsive cells that augment inflammation by producing pro-inflammatory mediators such as IL-17A, IL-22 and TNF. In addition, the molecular steps that translate inflammation into resident tissue responses, resulting in new bone formation, are discussed. The second part of the article summarizes the clinical features of Enthesitis, and the role of clinical and imaging instruments in detecting Enthesitis are discussed together with their challenges and limitations. Finally, the Review summarizes the current treatment possibilities for Enthesitis based on the aforementioned pathophysiological concepts, focusing on the role of cytokine-blocking agents. Entheses are predominantly extra-articularly localized structures that represent a key target of musculoskeletal inflammation in diseases such as psoriatic arthritis (PsA) and spondyloarthritis (SpA) Entheses contain a specific immune microenvironment, which is activated by a combination of factors that include mechanical stress, genetic susceptibility and microbial-triggered immune activation Enthesitis arises from robust activation of prostaglandin E2 and the IL-23–IL-17 axis, leading to the influx of innate immune cells and homing of inflammation into the entheses, which is followed by mesenchymal tissue responses and new bone formation Clinical and imaging instruments have been developed that enable the reliable detection and monitoring of Enthesitis in patients with PsA and SpA Inhibition of the key effector cytokines of Enthesitis — IL-17, IL-23 and TNF — has shown to be effective in supporting the resolution of Enthesitis in PsA and SpA This article provides an overview of the pathophysiology of Enthesitis, from induction and inflammation to tissue proliferation and bone formation. Building on these pathophysiological concepts, the clinical presentation, assessment and treatment of Enthesitis are also discussed.
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Enthesitis: from pathophysiology to treatment
Nature reviews. Rheumatology, 2017Co-Authors: Georg Schett, Bruce Kirkham, Rik Lories, Dirk Elewaut, Maria-antonietta D'agostino, Enrique R. Soriano, Dennis McgonagleAbstract:Entheses are the insertion sites of tendons and ligaments to the bone surface and are essential structures for locomotion. Inflammation of the entheses (Enthesitis) is a key feature of psoriatic arthritis and spondyloarthritis. To date, our conceptual understanding of Enthesitis remains limited. This Review provides an insight into the pathophysiology of Enthesitis, addressing the role of biomechanics, prostaglandin E2-mediated vasodilation and the activation of innate immune cells in the initiation phase of Enthesitis, as well as the role of entheseal IL-23-responsive cells that augment inflammation by producing pro-inflammatory mediators such as IL-17A, IL-22 and TNF. In addition, the molecular steps that translate inflammation into resident tissue responses, resulting in new bone formation, are discussed. The second part of the article summarizes the clinical features of Enthesitis, and the role of clinical and imaging instruments in detecting Enthesitis are discussed together with their challenges and limitations. Finally, the Review summarizes the current treatment possibilities for Enthesitis based on the aforementioned pathophysiological concepts, focusing on the role of cytokine-blocking agents.
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Can we improve the diagnosis of spondyloarthritis in patients with uncertain diagnosis? The EchoSpA prospective multicenter French cohort
Joint Bone Spine, 2012Co-Authors: Maria-antonietta D'agostino, Alain Saraux, Isabelle Chary-valckenaere, Christian Marcelli, Sandrine Guis, Philippe Gaudin, Philippe Aegerter, Sandrine Jousse-joulin, Damien Loeuille, Olivia JudetAbstract:Power Doppler ultrasound (PDUS) has proved to be a highly sensitive tool for assessing Enthesitis in spondyloarthritis (SpA). In patients with a suspected SpA, diagnosis could be improved by detecting Enthesitis with PDUS. OBJECTIVE: To evaluate the performance of PDUS for the diagnosis of SpA alone or combined with other clinical, laboratory and imaging findings in patients consulting for a suspected SpA. METHODS: Prospective, multicenter French cohort study (Boulogne-Billancourt, Brest, Caen, Grenoble, Marseille and Nancy). Outpatients consulting for symptoms suggestive of SpA (inflammatory back pain [IBP], arthritis or inflammatory arthralgia [IA], Enthesitis or dactylitis [ED], HLA-B27 positive uveitis [B27+U], familiarity for SpA [Fam]) were recruited and followed up for at least 2years. Sample size was set to 500 patients (for estimated prevalence of SpA of 30±5% after 2years). At baseline, patients were submitted to standardized physical examination, pelvic X-ray, sacroiliac joints magnetic resonance imaging (MRI), HLA-B typing, and other tests judged useful for diagnosis. For each patient, a blinded PDUS examination of 14 enthesitic sites was performed at baseline and at years 1 and 2. Patients were planned to be followed during 5years. The diagnosis of SpA ascertained by an experts' committee, blind to PDUS results, after at least 2years of follow-up, with a revaluation of doubtful patients at 5years will be used as gold standard for evaluating the diagnostic performance of PDUS and the best diagnostic procedure by combining PDUS, clinical symptoms and other tests. RESULTS: Between January 2005 and September 2007, 489 patients were included (96% of the target population). Nineteen patients (0.2%) retired their informed consensus or were lost to follow-up immediately after their inclusion. At baseline, mean age of the 470 remaining patients was 40years, mean duration of symptoms was 6.1years; 42% of them were HLA-B27+ and 63% were female. Primary inclusion criterion was IBP in 53%, IA in 27%, ED in 9%, B27+U in 8% and Fam in 4%. Follow-up is still ongoing. CONCLUSION: We have set up a unique diagnostic cohort which includes the entire spectrum of SpA manifestations. By using PDUS we expected to improve the diagnostic procedure of SpA.
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Ultrasound in the evaluation of Enthesitis: status and perspectives.
Arthritis research & therapy, 2011Co-Authors: Frédérique Gandjbakhch, Lene Terslev, Fredrick Joshua, Richard J. Wakefield, Esperanza Naredo, Maria-antonietta D'agostinoAbstract:An increasing number of studies have applied ultrasound to the evaluation of entheses in spondyloarthritis patients. However, no clear agreement exists on the definition of Enthesitis, on the number and choice of entheses to examine and on ultrasound technique, which may all affect the results of the examination. The objectives of this study were to first determine the level of homogeneity in the ultrasound definitions for the principal lesions of Enthesitis in the published literature and second, to evaluate the metric properties of ultrasound for detecting Enthesitis according to the OMERACT filter. Search was performed in PUBMED and EMBASE. Both grey-scale and Doppler definitions of Enthesitis, including describing features of Enthesitis, were collected and metrological qualities of studies were assessed. After selection, 48 articles were analyzed. The definition of ultrasound Enthesitis and elementary features varied among authors. Grey-scale Enthesitis was characterized by increasing thickness (94% of studies), hypoechogenicity (83%), enthesophytes (69%), erosions (67%), calcifications (52%), associated bursitis (46%) and cortical irregularities (29%). Only 46% of studies reported the use of Doppler. High discrepancies were observed on frequency, type of probe and Doppler mode used. Face and content validity were the most frequently evaluated criteria (43%) followed by reliability (29%) and responsiveness (19%). Ultrasound has evidence to support face, content validity and reliability for the evaluation of Enthesitis, though there is a lack of well-reported methodology in most of the studies. Consensus on elementary lesions and standardization of exam is needed to determine the ultrasound definition of Enthesitis in grey-scale and in Doppler for future applications.
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impact of guselkumab an interleukin 23 p19 subunit inhibitor on Enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis results from a randomised placebo controlled phase ii study
RMD Open, 2020Co-Authors: P J Mease, Dennis Mcgonagle, Dafna D Gladman, Atul Deodhar, Peter Nash, Wolfhenning Boehncke, Alice B Gottlieb, Elizabeth C Hsia, Chetan KaryekarAbstract:Objective To evaluate the effect of guselkumab on Enthesitis and dactylitis in a phase II trial of patients with active psoriatic arthritis (PsA). Methods This was a phase II, randomised, placebo-controlled, double-blind trial of adults with active PsA (≥3 swollen and ≥3 tender joints and C reactive protein ≥0.3 mg/dL) despite conventional synthetic disease-modifying anti-rheumatic drug, non-steroidal anti-inflammatory drug, and/or oral corticosteroid therapy. Patients were randomised to subcutaneous injections of guselkumab 100 mg or placebo at weeks 0, 4 and every 8 weeks, with placebo crossover to guselkumab at week 24. Dactylitis was scored on a scale of 0–3 on each digit; Enthesitis was assessed using the Leeds Enthesitis Index (0–6). Other assessments included American College of Rheumatology (ACR) and Psoriasis Area and Severity Index responses. Results Of 149 randomised patients, 107 patients had Enthesitis (mean score=2.7) and 81 patients had dactylitis (mean dactylitis score=5.7) at baseline. Mean improvements in Enthesitis and dactylitis at week 24 were greater in the guselkumab group versus placebo and sustained through week 56. Similar results were observed for the proportions of patients with resolution of Enthesitis and dactylitis. At week 56, mean improvements in Enthesitis and dactylitis among patients who switched from placebo to guselkumab treatment were similar to those in the guselkumab group. In the guselkumab group, ACR20 responders had greater improvements in Enthesitis and dactylitis versus non-responders (week 24). Conclusions At week 24, the guselkumab group had greater mean improvements in Enthesitis and dactylitis and greater proportions of patients with resolution of Enthesitis and dactylitis versus placebo. ACR20 response was associated with improvements in Enthesitis and dactylitis. Trial registration number ClinicalTrials.gov: NCT02319759. URL: https://clinicaltrials.gov/ct2/show/NCT02319759; Registered 18 December 2014.
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Ixekizumab and complete resolution of Enthesitis and dactylitis: integrated analysis of two phase 3 randomized trials in psoriatic arthritis.
Arthritis research & therapy, 2019Co-Authors: Dafna D Gladman, Ana Maria Orbai, Uta Klitz, James Cheng-chung Wei, Gaia Gallo, Julie Birt, Suchitrita S. Rathmann, David Shrom, Helena Marzo-ortegaAbstract:Ixekizumab improves signs/symptoms of psoriatic arthritis (PsA). We present an integrated analysis of baseline disease burden and post-baseline outcomes in ixekizumab-treated patients with Enthesitis or dactylitis. Data from SPIRIT-P1 and SPIRIT-P2 were integrated. Patients with PsA were randomized to 80-mg ixekizumab every 4 weeks (IXEQ4W) or 2 weeks (IXEQ2W), after a 160-mg starting dose, or to placebo. Inadequate responders at week 16 received rescue therapy. Among patients with baseline Enthesitis (Leeds Enthesitis Index [LEI] > 0) or dactylitis (Leeds Dactylitis Index-Basic [LDI-B] > 0), baseline characteristics and disease burden were reported. At week 24, LEI and LDI-B (percentage of patients with resolution [LEI = 0, LDI-B = 0]) were assessed. In pooled treatment groups, the impact of Enthesitis or dactylitis resolution on health-related quality of life (HRQoL) (EuroQol-5 Dimensions Visual Analogue Scale [EQ-5D VAS]), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and pain was assessed. The integrated analysis set comprised 679 patients; of these, 60% (n = 403 of 675) had baseline Enthesitis (LEI > 0) and 23% (n = 155 of 676) had baseline dactylitis (LDI > 0). At week 24, ixekizumab-treated patients experienced significantly more resolution than placebo of Enthesitis (39% IXEQ4W, 35% IXEQ2W, 21% placebo) and dactylitis (78% IXEQ4W, 65% IXEQ2W, 24% placebo). Furthermore, at entheseal points measured by the LEI, ixekizumab-treated patients had significantly higher resolution of Enthesitis compared to placebo. At week 24, among all placebo- and ixekizumab-treated patients, resolution of Enthesitis was associated with improvements in function and HRQoL whereas dactylitis resolution was associated with more limited improvements. The least squares mean HAQ-DI improvements from baseline were − 0.44 and − 0.25 for patients who did/did not resolve Enthesitis, and − 0.41 and − 0.31 for patients who did/did not resolve dactylitis. EQ-5D VAS improvements were 12.3 and 5.8 for patients who did/did not resolve Enthesitis, and 10.8 and 9.8 for patients who did/did not resolve dactylitis. Among patients with pre-existing Enthesitis or dactylitis, IXEQ2W- and IXEQ4W-treatment resulted in significant improvements in Enthesitis and dactylitis. Enthesitis resolution was associated with improvements in patients’ function, pain, and HRQoL. ClinicalTrials.gov, NCT01695239 , registered on September 25, 2012, and NCT02349295 , registered on October 10, 2014.
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therapeutic benefit of apremilast on Enthesitis and dactylitis in patients with psoriatic arthritis a pooled analysis of the palace 1 3 studies
RMD Open, 2018Co-Authors: Dafna D Gladman, Arthur Kavanaugh, Benoît Guérette, Juan J Gomezreino, J Wollenhaupt, Eric Lespessailles, Georg Schett, N Delev, Maurizio Cutolo, L TengAbstract:Objective The Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) clinical trial programme findings demonstrated that apremilast, an oral phosphodiesterase 4 inhibitor, is effective for treating psoriatic arthritis (PsA). Enthesitis and dactylitis are difficult-to-treat features of PsA leading to disability and affecting quality of life. PALACE 1, 2 and 3 data were pooled to assess the efficacy of apremilast on Enthesitis and dactylitis outcomes in patients with these conditions at baseline. Methods Patients with Enthesitis (n=945) or dactylitis (n=633) at baseline were analysed after receiving double-blind treatment with placebo, apremilast 30 mg two times per day or apremilast 20 mg two times per day up to 52 weeks and continuing up to 5 years. Data were analysed through 156 weeks. Enthesitis was evaluated by Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and dactylitis via dactylitis count. Results At week 24, patients receiving apremilast 30 mg two times per day demonstrated a significantly greater mean change in Enthesitis (−1.3 vs −0.9; p Conclusion Apremilast is effective for the treatment of active PsA, including improvements in Enthesitis and dactylitis up to 3 years. Trial registration numbers NCT01172938, NCT01212757 and NCT01212770.
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The Association Between HLA Genetic Susceptibility Markers and Sonographic Enthesitis in Psoriatic Arthritis.
Arthritis & rheumatology (Hoboken N.J.), 2018Co-Authors: Ari Polachek, Dafna D Gladman, Vinod Chandran, Richard J. Cook, Fatima Abji, Lihi EderAbstract:Objective Enthesitis is an important pathophysiologic component of psoriatic arthritis (PsA). HLA genes are implicated in the pathogenesis of PsA. Little is known about the relationship between HLA genetic susceptibility markers and Enthesitis in PsA patients. Our aim was to examine the association between HLA genetic susceptibility markers and sonographic Enthesitis in PsA. Methods A cross-sectional analysis was conducted in patients with PsA. Sonographic Enthesitis was assessed according to the Madrid Sonography Enthesitis Index scoring system. HLA genotyping was performed using sequence-specific oligonucleotide probes. The association between 6 HLA susceptibility markers of PsA and the severity of sonographic Enthesitis was assessed using multivariate regression models adjusted for age, sex, body mass index, and disease duration. Results Two hundred twenty-five patients were included, 57.8% of whom were men. The mean ± SD age was 56.1 ± 12.7 years, and the mean ± SD PsA duration was 16.9 ± 12.3 years. In the multivariate regression model, HLA-B*27 was associated with a higher Enthesitis score (β = 4.24 [95% confidence interval {95% CI} 0.02, 8.46]), and the interaction between HLA-B*27 and PsA duration was statistically significant, showing an increasing effect of HLA-B*27 with longer PsA duration (β = 4.62 [95% CI 1.38, 7.86]). Conclusion HLA-B*27 is associated with more severe sonographic Enthesitis in PsA, particularly in patients with longer disease duration. This finding highlights the possible role of genetic variants in predisposing to PsA subphenotypes.
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Clinical Enthesitis in a Prospective Longitudinal Psoriatic Arthritis Cohort: Incidence, Prevalence, Characteristics, and Outcome.
Arthritis care & research, 2017Co-Authors: Ari Polachek, Vinod Chandran, Dafna D GladmanAbstract:Objectives: The aim of our study was to evaluate the incidence, prevalence, characteristics, disease associations, risk factors and outcome of clinical Enthesitis in patients with PsA. Methods: The study included patients with PsA followed prospectively. Enthesitis was defined as the presence of at least one tender enthesis at one of the 18 entheseal sites of the Spondyloarthritis Research Consortium of Canada Enthesitis index. Results: Between 2008 and 2014, 281 of 803 patients had Enthesitis providing a prevalence of 35%. 192 patients developed Enthesitis during the course of follow-up, with an annual incidence of 0.9%. Most of the patients had 1 (48.4%) or 2 (32.2%) tender entheseal sites and the mean (s.d.) number of sites per visit was 2.03 (1.6). The 3 most common sites were at the insertions of the Achilles tendons and plantar fascia on the calcaneus, and the lateral epicondyles (24.2%, 20.8% and 17.2%, respectively). More active disease (higher actively inflamed joint count, tenosynovitis and dactylitis), more pain and less clinical damage were associated with Enthesitis. Higher BMI, more actively inflamed joints and younger age were risk factors for developing this condition. Enthesitis resolved in most patients without changing treatment. Conclusion: Clinical Enthesitis is common with a period prevalence of 35% of PsA patients. It usually involves only 1 or 2 sites simultaneously. The most common tender sites are at the insertions of the Achilles tendon, plantar fascia and the lateral epicondyles. More active disease and more pain are associated with Enthesitis. This article is protected by copyright. All rights reserved.