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Liu WJ, Wang JX, Li QF, Zhang YH, Ji PF, Jin JH, Zhang YB, Yuan ZH, Feng P, Wu YF, Shen HY, Wang P. Fat mass and obesity-associated protein in mesenchymal stem cells inhibits osteoclastogenesis via lnc NORAD/miR-4284 axis in ankylosing spondylitis. World J Stem Cells 2025; 17:98911. [PMID: 40160686 PMCID: PMC11947893 DOI: 10.4252/wjsc.v17.i3.98911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 01/03/2025] [Accepted: 02/26/2025] [Indexed: 03/21/2025] Open
Abstract
BACKGROUND Ankylosing spondylitis (AS) is recognized as a long-term inflammatory disorder that leads to inflammation in the spine and joints, alongside abnormal bone growth. In previous studies, we reported that mesenchymal stem cells (MSCs) derived from individuals with AS demonstrated a remarkable inhibition in the formation of osteoclasts compared to those obtained from healthy donors. The mechanism through which MSCs from AS patients achieve this inhibition remains unclear. AIM To investigate the potential underlying mechanism by which MSCs from individuals with ankylosing spondylitis (AS-MSCs) inhibit osteoclastogenesis. METHODS We analysed fat mass and obesity-associated (FTO) protein levels in AS-MSCs and MSCs from healthy donors and investigated the effects and mechanism by which FTO in MSCs inhibits osteoclastogenesis by coculturing and measuring the levels of tartrate-resistant acid phosphatase, nuclear factor of activated T cells 1 and cathepsin K. RESULTS We found that FTO, an enzyme responsible for removing methyl groups from RNA, was more abundantly expressed in MSCs from AS patients than in those from healthy donors. Reducing FTO levels was shown to diminish the capacity of MSCs to inhibit osteoclast development. Further experimental results revealed that FTO affects the stability of the long non-coding RNA activated by DNA damage (NORAD) by altering its N6-methyladenosine methylation status. Deactivating NORAD in MSCs significantly increased osteoclast formation by affecting miR-4284, which could regulate the MSC-mediated inhibition of osteoclastogenesis reported in our previous research. CONCLUSION This study revealed elevated FTO levels in AS-MSCs and found that FTO regulated the ability of AS-MSCs to inhibit osteoclast formation through the long noncoding RNA NORAD/miR-4284 axis.
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Affiliation(s)
- Wen-Jie Liu
- Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
- Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
| | - Jia-Xin Wang
- Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
- Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
| | - Quan-Feng Li
- Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
- Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
| | - Yun-Hui Zhang
- Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
- Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
| | - Peng-Fei Ji
- Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
- Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
| | - Jia-Hao Jin
- Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
- Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
| | - Yi-Bin Zhang
- Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
- Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
| | - Zi-Hao Yuan
- Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
- Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
| | - Pei Feng
- Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
- Center for Biotherapy, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
| | - Yan-Feng Wu
- Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
- Center for Biotherapy, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
| | - Hui-Yong Shen
- Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
- Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
| | - Peng Wang
- Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China
- Guangdong Provincial Clinical Research Center for Orthopedic Diseases, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen 518033, Guangdong Province, China.
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Chen X, Li P, Wang G. Development of a fluorescent probe for detecting superoxide anions for monitoring the progression and treatment of acute spondylitis. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2025; 17:533-538. [PMID: 39656111 DOI: 10.1039/d4ay01626b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2025]
Abstract
The superoxide anion (O2˙-) is a vital reactive oxygen species (ROS) and participates in various physiological and pathological processes in organisms. The outbreak of O2˙- in the endoplasmic reticulum (ER) is believed to be closely related to many inflammatory diseases. In this work, a turn-on type ER-targeting fluorescent probe ERO was rationally designed for sensitive and selective detection of O2˙-. The minimum detection limit concentration for O2˙- was about 3.3 × 10-7 M in aqueous solution. More importantly, the probe ERO has minimal biological toxicity and can effectively target the ER and detect O2˙- in macrophage cells. Resveratrol is a natural drug closely related to anti-inflammatory effects. Through fluorescence monitoring of the probe ERO, it was found that there was an outbreak of O2˙- in the ER in acute spondylitis in mice and resveratrol reversed this increase. Thus, the probe ERO has the potential to become a favorable diagnostic tool to visualize the mouse spine during inflammation and the therapeutic effect of resveratrol.
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Affiliation(s)
- Xiaoming Chen
- Department of Spinal Surgery, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China.
| | - Peng Li
- Department of Spinal Surgery, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China.
| | - Guiqing Wang
- Department of Spinal Surgery, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, China.
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Chen Y, Liu M, Lu M, Luo L, Han Z, Liu X. Exploring the impact of m 6A modification on immune diseases: mechanisms and therapeutic implication. Front Immunol 2024; 15:1387582. [PMID: 39072324 PMCID: PMC11272477 DOI: 10.3389/fimmu.2024.1387582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 06/28/2024] [Indexed: 07/30/2024] Open
Abstract
N6-methyladenosine (m6A) is a chemical modification of RNA and has become a widely discussed topic among scientific researchers in recent years. It is distributed in various organisms, including eukaryotes and bacteria. It has been found that m6A is composed of writers, erasers and readers and is involved in biological functions such as splicing, transport and translation of RNA. The balance of the human immune microenvironment is important for human health abnormalities. Increasing studies have found that m6A affects the development of immune diseases such as inflammatory enteritis and systemic lupus erythematosus (SLE) by participating in the homeostatic regulation of the immune microenvironment in vivo. In this manuscript, we introduce the composition, biological function, regulation of m6A in the immune microenvironment and its progression in various immune diseases, providing new targets and directions for the treatment of immune diseases in clinical practice.
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Affiliation(s)
- Yutong Chen
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Min Liu
- Department of Traditional Chinese Medicine, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, China
| | - Miao Lu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Linling Luo
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhongyu Han
- School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xide Liu
- Department of Traditional Chinese Medicine, Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, China
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Early Improvements in Disease Activity Indices Predict Long-Term Clinical Remission Suggested by the Treat-to-Target Strategy in Patients with Ankylosing Spondylitis Receiving TNF-α Inhibitor Treatment. J Clin Med 2021; 10:jcm10184279. [PMID: 34575390 PMCID: PMC8469764 DOI: 10.3390/jcm10184279] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 08/29/2021] [Accepted: 09/16/2021] [Indexed: 01/12/2023] Open
Abstract
This study evaluated the possibility of clinical remission suggested by the treat-to-target strategy and identified predictors of clinical remission in 139 patients with ankylosing spondylitis (AS) receiving tumor necrosis factor-α inhibitors (TNFi). Clinical remission criteria selected were AS Disease Activity Score Inactive Disease (ASDAS-ID) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 2 with normal C-reactive protein (CRP) levels (BASDAI-CRP). The longitudinal relationship between clinical parameters and clinical remission was assessed using generalized estimating equations (GEEs). Responders to ASDAS-ID and BASDAI-CRP increased from 32.4% to 68.9% and from 39.9% to 75.2% at months 3 and 33, respectively. Responders to ASDAS-ID and BASDAI-CRP almost overlapped. In the univariable GEE model, age and 3-month improvement in BASDAI, ASDAS-CRP, physician and patient global assessments, and spinal pain predicted clinical remission achievement, while the presence of syndesmophytes predicted ASDAS-CRP achievement, and normalized CRP at 3 months was associated with BASDAI-CRP achievement. Multivariable GEE analysis revealed age (odds ratio (OR): 0.67; 95% confidence interval (CI), 0.49–0.93) and 3-month BASDAI improvement (OR: 1.70; CI, 1.19–2.41) as independent predictors of ASDAS-ID achievement and age (OR: 0.69; CI, 0.54–0.89), 3-month BASDAI improvement (OR: 2.00; CI, 1.45–2.76), and normalized CRP at 3 months (OR: 3.72; CI, 1.39–9.95) as independent predictors of BASDAI-CRP achievement.
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Molina Collada J, Trives L, Castrejón I. The Importance of Outcome Measures in the Management of Inflammatory Rheumatic Diseases. Open Access Rheumatol 2021; 13:191-200. [PMID: 34285602 PMCID: PMC8285275 DOI: 10.2147/oarrr.s276980] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/24/2021] [Indexed: 11/23/2022] Open
Abstract
Rheumatic inflammatory diseases include a diverse and heterogeneous group of multifaceted disorders in which clinical history and physical examination are essential to make treatment choices and for optimizing outcomes. Composite outcome measures have become very relevant in rheumatology to evaluate disease activity as they capture the most important dimensions of the disease into one single measure. Most outcome measures may include disease manifestations, laboratory data, physician examination as well as the patient perspective as different outcome dimensions of the disease into a simple index. These outcome measures have proved their utility for guiding treatment in treat-to- target strategies and personalized medicine, with remission being the ultimate goal. In this narrative review, we go over the most commonly used outcome measures in rheumatoid arthritis, spondyloarthropathies, including psoriatic arthritis, and systemic lupus erythematosus to provide a practical summary for clinicians for everyday routine care.
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Affiliation(s)
- Juan Molina Collada
- Department of Rheumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.,Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Laura Trives
- Department of Rheumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Isabel Castrejón
- Department of Rheumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.,Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
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Cruz-Machado AR, Rodrigues-Manica S, Silva JL, Alho I, Coelho C, Duarte J, Florêncio C, Pimentel-Santos FM, Tavares-Costa J, Vieira-Sousa E. Effect of biologic disease-modifying anti-rheumatic drugs targeting remission in axial spondyloarthritis: systematic review and meta-analysis. Rheumatology (Oxford) 2020; 59:3158-3171. [PMID: 32696064 DOI: 10.1093/rheumatology/keaa268] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 03/17/2020] [Accepted: 04/08/2020] [Indexed: 01/20/2023] Open
Abstract
OBJECTIVES To assess the efficacy of biologic DMARDs (bDMARDs) in achieving Assessment of Spondyloarthritis International Society partial remission (ASAS-PR) and/or Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS-ID), as remission-like surrogates, in axial SpA (axSpA). METHODS Data from randomized controlled trials (RCTs), including long-term extensions, were included. A systematic literature review was performed using the MEDLINE database (first search May 2018, updated February 2020) and PICO criteria according to Patients-adults with radiographic or non-radiographic axSpA; Intervention-any bDMARD; Comparator-placebo and/or any different drug; Outcomes-ASAS-PR and/or ASDAS-ID as primary or secondary endpoints. Meta-analysis was performed after assessment of the homogeneity of study designs, populations and outcomes. RESULTS After screening 155 references, a total of 22 RCTs and 28 long-term extensions were retrieved. ASAS-PR was the dominant remission-like definition used. Concerning TNF inhibitors, 14/17 RCTs provided evidence of efficacy in reaching remission at different time points: 12, 16, 24 and 28 weeks (ASAS-PR in 16-62% of patients and ASDAS-ID in 24-40% of patients). With a limited number of studies available, IL-17A inhibitors exhibited remission rates of 15-21% for ASAS-PR and 11-16% for ASDAS-ID at week 16. A meta-analysis regarding ASAS-PR was performed considering RCTs with a similar duration (12, 16 or 24 weeks). The relative risk for achieving remission was 3.864 (95% CI 2.937, 5.085). CONCLUSION bDMARDs have a clear impact in axSpA remission evaluated by ASAS-PR. Nevertheless, these data show an unmet need for improved reporting of remission-like outcomes.
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Affiliation(s)
- Ana Rita Cruz-Machado
- Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon Academic Medical Centre, Lisbon, Portugal.,Rheumatology Research Unit, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Santiago Rodrigues-Manica
- Rheumatology Department, Hospital Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal.,CEDOC, NOVA Medical School, Lisbon, Portugal
| | - Joana Leite Silva
- Rheumatology Department, Unidade Local de Saúde do Alto Minho, Ponte de Lima, Portugal
| | - Irina Alho
- Genetics Laboratory, Institute of Environmental Health, Lisbon Medical School, University of Lisbon, Lisbon, Portugal
| | - Constança Coelho
- Genetics Laboratory, Institute of Environmental Health, Lisbon Medical School, University of Lisbon, Lisbon, Portugal
| | - Joana Duarte
- Medical Department, Novartis Pharma, Porto Salvo, Portugal
| | | | - Fernando M Pimentel-Santos
- Rheumatology Department, Hospital Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal.,CEDOC, NOVA Medical School, Lisbon, Portugal
| | - José Tavares-Costa
- Rheumatology Department, Unidade Local de Saúde do Alto Minho, Ponte de Lima, Portugal
| | - Elsa Vieira-Sousa
- Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon Academic Medical Centre, Lisbon, Portugal.,Rheumatology Research Unit, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
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Krabbe S, Eshed I, Sørensen IJ, Møller J, Jensen B, Madsen OR, Klarlund M, Pedersen SJ, Østergaard M. Novel whole-body magnetic resonance imaging response and remission criteria document diminished inflammation during golimumab treatment in axial spondyloarthritis. Rheumatology (Oxford) 2020; 59:3358-3368. [PMID: 32310294 DOI: 10.1093/rheumatology/keaa153] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Revised: 02/24/2020] [Indexed: 01/20/2023] Open
Abstract
OBJECTIVES To investigate criteria for treatment response and remission in patients with axial SpA as assessed by whole-body magnetic resonance imaging (WB-MRI) of axial and peripheral joints and entheses during treatment with golimumab. METHODS We performed an investigator-initiated cohort study of 53 patients who underwent WB-MRI at weeks 0, 4, 16 and 52 after initiation of golimumab. Images were assessed according to the Spondyloarthritis Research Consortium of Canada MRI SI joint inflammation index, Canada-Denmark MRI spine inflammation score and the MRI peripheral joints and entheses inflammation index. RESULTS At weeks 4, 16 and 52, WB-MRI demonstrated an at least 50% reduction of MRI inflammation of the sacroiliac joints in 16, 29 and 32 (30%, 55% and 60%) patients, of the spine in 20, 30 and 31 (38%, 57% and 58%) patients and of peripheral joints and entheses in 8, 17 and 15 (15%, 32% and 28%) patients, respectively. The BASDAI50 response was achieved by 29, 31 and 31 (55%, 58% and 58%) patients, while ASDAS clinically important improvement (ASDAS-CII) was achieved by 37, 40 and 34 (70%, 75% and 64%) patients. WB-MRI remission criteria for spine, sacroiliac joints and peripheral joints and entheses were explored; total WB-MRI remission was attained by 2, 6 and 3 (4%, 11% and 6%) patients. At week 16, among 35 patients with an at least 50% reduction in the MRI Axial Inflammation Index (sacroiliac joint and spine inflammation), 29 (83%) achieved BASDAI50 and 35 (100%) achieved ASDAS-CII; among 16 patients with MRI axial inflammation non-response, 14 (88%) were BASDAI50 non-responders and 11 (69%) did not achieve ASDAS-CII. CONCLUSION WB-MRI demonstrated a significant reduction of inflammation in both the spine, sacroiliac joints and peripheral joints and entheses during golimumab treatment. Few patients achieved total WB-MRI remission. Combining spinal and sacroiliac joint inflammation in an MRI Axial Inflammation Index increased the ability to capture response. TRIAL REGISTRATION ClinicalTrials.gov, http://clinicaltrials.gov, NCT02011386.
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Affiliation(s)
- Simon Krabbe
- Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Iris Eshed
- Department of Diagnostic Imaging, Sheba Medical Center, Affiliated to the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Inge J Sørensen
- Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jakob Møller
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Radiology, Herlev and Gentofte Hospital, Herlev, Denmark
| | - Bente Jensen
- Center for Rheumatology and Spine Diseases, Frederiksberg Hospital, Frederiksberg, Denmark
| | - Ole R Madsen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Center for Rheumatology and Spine Diseases, Herlev and Gentofte Hospital, Hellerup, Denmark
| | - Mette Klarlund
- Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark
| | - Susanne J Pedersen
- Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Center for Rheumatology and Spine Diseases, Herlev and Gentofte Hospital, Hellerup, Denmark
| | - Mikkel Østergaard
- Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Liew JW, Dubreuil M. Treat to Target in Axial Spondyloarthritis: Pros, Cons, and Future Directions. Rheum Dis Clin North Am 2020; 46:343-356. [PMID: 32340706 PMCID: PMC8106802 DOI: 10.1016/j.rdc.2020.01.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Treat to target describes a management paradigm that involves choosing a clinically relevant target, assessment with validated measures at a prespecified frequency, and a change in therapy if the target is not met. Although guidelines recommend treating to target in axial spondyloarthritis (axSpA), ideal methods to reach this target remain controversial. This review focuses on background for a treat-to-target strategy in axSpA. Potential targets of treatment, association of targets with outcomes, evidence of treatment impact on outcomes, and how treat to target has been incorporated into treatment guidelines are discussed. Treat-to-target trials and the research agenda for studies in axSpA are discussed.
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Affiliation(s)
- Jean W Liew
- Division of Rheumatology, Department of Medicine, University of Washington, 1959 Northeast Pacific Street, BB561, Seattle, WA 98195, USA. https://twitter.com/rheum_cat
| | - Maureen Dubreuil
- Section of Rheumatology, Boston University School of Medicine, 650 Albany Street, X201, Boston, MA 02119, USA.
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Lawson DO, Eraso M, Mbuagbaw L, Joanes M, Aves T, Leenus A, Omar A, Inman RD. Tumor Necrosis Factor Inhibitor Dose Reduction for Axial Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Arthritis Care Res (Hoboken) 2020; 73:861-872. [PMID: 32166872 DOI: 10.1002/acr.24184] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 03/03/2020] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The present study was undertaken to investigate the effectiveness and safety of dose reduction of tumor necrosis factor inhibitor (TNFi) therapy in the treatment of axial spondyloarthritis (SpA) compared to usual care. METHODS We searched the Cochrane Central Register of Controlled Trials, Embase, Medline, and trial registries. We screened, extracted data, and assessed risk of bias in duplicate. Data were pooled using random-effects models; subgroup analyses were performed for type of TNFi, prior TNFi exposure, and follow-up duration. Outcomes of interest were Assessment of SpondyloArthritis international Society (ASAS) response and remission criteria, disease activity, relapse, and safety. RESULTS We included 6 randomized trials with 747 participants (442 with ankylosing spondylitis and 305 with nonradiographic axial SpA). Compared to the standard dose, there were fewer events with the reduced dose for the ASAS criteria for 40% improvement (risk ratio [RR] 0.62 [95% confidence interval (95% CI) 0.49, 0.78]) and for ASAS partial remission (RR 0.17 [95% CI 0.06, 0.46]). There was a mean increase in the Bath Ankylosing Spondylitis Disease Activity Index score (mean difference [MD] 0.35 [95% CI 0.10, 0.60]) and no difference in C-reactive protein levels (MD 0.16 [95% CI -0.76, 1.07]) with the reduced dose. There were more disease flares/relapses (RR 1.73 [95% CI 1.32, 2.27]) with the reduced dose. There were no differences in infection rates (incidence rate ratio [IRR] 0.98 [95% CI 0.76, 1.25]) or injection/infusion reactions (IRR 0.71 [95% CI 0.42, 1.19]). CONCLUSION Patients with axial SpA may experience little to no clinical benefit from reduction of TNFi therapy. Maintaining the standard dose probably improves the sustained effect on disease activity and helps to prevent disease flare.
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Affiliation(s)
- Daeria O Lawson
- McMaster University, Hamilton, and Toronto Western Hospital, Toronto, Ontario, Canada
| | - Maria Eraso
- Toronto Western Hospital, Toronto, Ontario, Canada
| | - Lawrence Mbuagbaw
- McMaster University and St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada
| | | | - Theresa Aves
- St. Michael's Hospital, Toronto, Ontario, Canada
| | | | - Ahmed Omar
- Toronto Western Hospital, Toronto, Ontario, Canada
| | - Robert D Inman
- Toronto Western Hospital, University of Toronto, and Toronto Western Hospital, Toronto, Ontario, Canada
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Marzo-Ortega H, Gaffney KM, Gaffney K. Defining the target: clinical aims in axial spondyloarthritis. Rheumatology (Oxford) 2019; 57:vi18-vi22. [PMID: 30445481 PMCID: PMC6238221 DOI: 10.1093/rheumatology/key176] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Indexed: 12/17/2022] Open
Abstract
Treat-to-target (T2T) is an emerging treatment paradigm in axial spondyloarthritis (axSpA), originally based on evidence from other inflammatory conditions, which aims to direct therapy to a clear target such as disease remission or low disease activity, with the ultimate goal of maximizing quality of life in affected individuals. The 2016 update of the Assessment of Spondyloarthritis International Society/EULAR guidelines for axSpA have recommended that treatment should be guided according to a predefined target but controversy remains as to what this target should be. An international task force has recommended remission or inactive disease as the desired outcome; however, there are many disease outcome measures developed for use in clinical practice in axSpA and the question remains of which is the most appropriate to use. Another important consideration when discussing the T2T paradigm is when to intervene. Although evidence is limited in this respect, the available data suggest that therapy should be commenced at an early stage of the disease, when the process of bone repair expected to occur after an inflammatory phase has not yet started. It has also been argued that the success of the T2T paradigm may depend more on the treatment strategy than the individual therapies utilized. This article will explore the feasibility of using a T2T approach in axSpA clinical practice, the utilization of new composite outcome measures of disease activity such as the ASDAS, and the validity of different treatment strategies to allow for a T2T intervention in these patients.
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Affiliation(s)
- Helena Marzo-Ortega
- NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust.,Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds
| | - Katie M Gaffney
- NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust.,Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds
| | - Karl Gaffney
- Rheumatology Department, Norfolk and Norwich University Hospital, Norwich, UK
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Codreanu C, Šírová K, Jarošová K, Batalov A. Assessment of effectiveness and safety of biosimilar infliximab (CT-P13) in a real-life setting for treatment of patients with active rheumatoid arthritis or ankylosing spondylitis. Curr Med Res Opin 2018; 34:1763-1769. [PMID: 29439591 DOI: 10.1080/03007995.2018.1441144] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVE To assess the effectiveness and safety of infliximab biosimilar, CT-P13, administered in a real-life setting to adult patients with active rheumatoid arthritis (RA) or ankylosing spondylitis (AS). METHODS This multi-center, non-interventional, observational study was conducted in Bulgaria, the Czech Republic, and Romania. A total of 151 patients with severe active RA (n = 81) or AS (n = 70) were enrolled and treated with CT-P13 for 24 weeks, according to current medical recommendations. Effectiveness was assessed using the 4-item Disease Activity Score 28 with C-reactive protein (DAS28-CRP) for RA patients, and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS patients. Safety was assessed by withdrawals and adverse events (AEs). RESULTS A total of 129 patients (RA: 67; AS: 62) were included in the effectiveness analysis. CT-P13 treatment significantly improved DAS28-CRP scores at 12 and 24 weeks (p = .0001 vs baseline for both timepoints) in patients with RA and BASDAI scores at 12 and 24 weeks (p = .0001 vs baseline for both timepoints) in patients with AS. CRP levels were significantly reduced at 12 and 24 weeks (p = .0001 vs baseline for both timepoints). Among 713 infusions, 34 AEs were reported (4.8% of infusions), of which 11 were considered related to CT-P13 treatment. Two of seven serious AEs were considered possibly (hepatocellular injury) or definitely (dyspnoea due to allergic infusion reaction) treatment-related. Eight patients discontinued CT-P13 due to AEs and four patients were withdrawn due to therapeutic failure. CONCLUSIONS CT-P13 was effective and safe in a real-life setting in patients with active RA or AS.
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Affiliation(s)
- Cătălin Codreanu
- a Center for Rheumatic Diseases , University of Medicine and Pharmacy , Bucharest , Romania
| | - Klára Šírová
- b Revmatologie , Revmatologie MU Dr. Klara Sirova, sro , Ostrava , Czech Republic
| | | | - Anastas Batalov
- d Rheumatology , Medical University of Plovdiv, UMHAT "Kaspela" , Plovdiv , Bulgaria
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Bergman M, Lundholm A. Managing morbidity and treatment-related toxicity in patients with ankylosing spondylitis. Rheumatology (Oxford) 2018; 57:419-428. [PMID: 28977661 PMCID: PMC5850804 DOI: 10.1093/rheumatology/kex292] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2016] [Indexed: 12/17/2022] Open
Abstract
AS is the prototypical member of the family of spondyloarthropathies, and is characterized by seronegativity, axial predominance and new bone formation, which underlie symptoms of inflammatory back pain, enthesopathy and extra-articular manifestations, including anterior uveitis, psoriasis and colitis. Patients with AS typically experience a wide variety of morbidities. These include both morbidities related to the disease itself—most prominently progressive, irreversible, structural damage to the axial or peripheral skeleton—and morbidities stemming from treatments for the disease, including toxicities from NSAID use, and increased risk of infections and immunogenicity concerns with biologics. AS is also associated with a number of comorbidities. We review the risks associated with AS, its comorbidities and its treatments, as well as strategies that can be used to mitigate these risks in patients with AS.
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Affiliation(s)
- Martin Bergman
- Department of Medicine, Drexel University College of Medicine, PA, USA
| | - Amy Lundholm
- Rheumatology, Lankenau Medical Center, Wynnewood, PA, USA
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BARALIAKOS XENOFON, BERENBAUM FRANCIS, FAVALLI ENNIOGIULIO, OLIVIERI IGNAZIO, OSTENDORF BENEDIKT, PODDUBNYY DENIS, DE VLAM KURT. Challenges and Advances in Targeting Remission in Axial Spondyloarthritis. J Rheumatol 2018; 45:153-157. [DOI: 10.3899/jrheum.170222] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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14
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Garrido-Cumbrera M, Hillmann O, Mahapatra R, Trigos D, Zajc P, Weiss L, Bostynets G, Gossec L, Coates LC. Improving the Management of Psoriatic Arthritis and Axial Spondyloarthritis: Roundtable Discussions with Healthcare Professionals and Patients. Rheumatol Ther 2017; 4:219-231. [PMID: 28600789 PMCID: PMC5696278 DOI: 10.1007/s40744-017-0066-2] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Indexed: 12/17/2022] Open
Abstract
Psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA) are both chronic, inflammatory conditions that result in a substantial burden of disease and reduced quality of life for patients. Patient involvement in developing optimal disease management strategies, including defining appropriate goals, therapies, and treatment options, as well as in setting policy priorities and agendas, is key. A working group of patient organization representatives and rheumatologists explored what patients consider to be unmet needs, important treatment gaps, and future priorities in PsA and AxSpA management. Reducing pain and fatigue, and improving physical and social functioning and work productivity were identified as important treatment goals for patients. Although the major treatment target for both PsA and AxSpA is remission, with low/minimal disease activity an alternative target for patients with established or long-standing disease, the meaning of remission from the patient's perspective needs to be explored further as it may differ considerably from the physician's perspective. Key recommendations from the working group to tackle unmet needs included reducing time to diagnosis, increasing patient and physician disease awareness, focusing on patients' priorities for treatment goals, and improving patient-physician communication. By addressing these key action points moving forward, the hope is that outcomes will continue to improve for patients with PsA and AxSpA.
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Affiliation(s)
- Marco Garrido-Cumbrera
- CEADE (Coordinadora Española de Asociaciones de Pacientes de Espondiloartritis), Universidad de Sevilla, Seville, Spain
| | - Ottfrid Hillmann
- EUROPSO (European Umbrella Organisation for Psoriasis Movements), Almere, The Netherlands
| | - Raj Mahapatra
- ASIF (Ankylosing Spondylitis International Federation), London, UK
| | | | - Petra Zajc
- Slovenian Association of Rheumatic Patients, Ljubljana, Slovenia
| | - Luisa Weiss
- Schweizerische Polyarthritiker-Vereinigung, Zurich, Switzerland
| | | | - Laure Gossec
- Sorbonne Université, Paris 06 Univ, Paris, France
- Rheumatology Department, Hôpital Pitié Salpêtrière, AP-HP, Paris, France
| | - Laura C Coates
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
- Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
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Han R, Yang X, Chen M, Zhang X, Yuan Y, Hu X, Wang M, Liu R, Ma Y, Yang J, Xu S, Shuai Z, Jiang S, Pan F. Changes and clinical significance of CD8+CD122+ T cells in the peripheral blood of patients with ankylosing spondylitis. Clin Rheumatol 2017; 37:639-646. [DOI: 10.1007/s10067-017-3887-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2017] [Revised: 10/11/2017] [Accepted: 10/23/2017] [Indexed: 01/01/2023]
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Danve A, Deodhar A. Treat to Target in Axial Spondyloarthritis: What Are the Issues? Curr Rheumatol Rep 2017; 19:22. [PMID: 28386759 DOI: 10.1007/s11926-017-0648-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE OF THE REVIEW Treat to Target (T2T) strategy has been widely used in the management of chronic medical conditions, such as hypertension, diabetes, and hypothyroidism, as well as rheumatic diseases, such as rheumatoid arthritis and gout. The purpose of this review is to discuss the importance, feasibility, and challenges in adopting the T2T strategy for the management of axial spondyloarthritis (axSpA). RECENT FINDINGS In 2014, a panel of international experts published recommendations for T2T in axSpA. Recent Tight Control of Inflammation in Early Psoriatic Arthritis (TICOPA) trial demonstrated efficacy of T2T in the management of the psoriatic arthritis. However, there are several issues in the adoption of T2T in axSpA. They include lack of evidence of the impact of aggressive management on clinical and radiographic outcomes in axSpA and unavailability of a definite target for the treatment, as well as limited therapeutic options. In this review, we discuss the intricacies of the T2T strategy in axSpA. We need more clinical evidence in the form of randomized clinical studies to assess the impact of T2T on outcomes in axSpA. We also need a definite target which is useful in the routine clinical practice, as well as for clinical trials.
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Affiliation(s)
- Abhijeet Danve
- Division of Rheumatology, Yale University School of Medicine, New Haven, CT, 06519, USA
| | - Atul Deodhar
- Division of Arthritis & Rheumatic diseases, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
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Dougados M, Perrot S. Fibromyalgia and central sensitization in chronic inflammatory joint diseases. Joint Bone Spine 2017; 84:511-513. [DOI: 10.1016/j.jbspin.2017.03.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/14/2016] [Indexed: 10/20/2022]
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18
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Monti S, Todoerti M, Codullo V, Favalli EG, Biggioggero M, Becciolini A, Montecucco C, Caporali R. Prevalence of Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease in a cohort of patients treated with TNF-alpha inhibitors. Mod Rheumatol 2017; 28:542-549. [PMID: 28880727 DOI: 10.1080/14397595.2017.1367076] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Treat to target (T2T), aiming at inactive disease (ID), has become the recommended strategy for axial-SpA (ax-SpA). Using the Ankylosing Spondylitis Disease Activity Score (ASDAS), we assessed the prevalence of ID in ax-SpA patients treated with TNFα inhibitors (TNFi). METHODS A multicentric, cross-sectional study was performed assessing disease activity status (BASDAI and ASDAS) of consecutive patients with ax-SpA on stable treatment with TNFi for at least six months. We analyzed differences with nonradiographic axSpA (nr-ax-SpA) and the influence of population characteristics and comorbidities in reaching ID. ID was defined as ASDAS-CRP <1.3. RESULTS A total of 218 patients were enrolled, 165 with AS and 53 with nr-ax-SpA. ASDAS-CRP ID was reached by 89 (40.8%) patients, while 163 (74.8%) of patients achieved good disease control with BASDAI. There were no significant differences between the two diagnostic groups. Multivariate logistic regression demonstrated a negative correlation of concomitant fibromyalgia, higher BASMI and current NSAIDs with the chances of reaching ASDAS-CRP ID or BASDAI <4. CONCLUSION T2T represents a new challenge in the management of ax-SpA, with recently introduced disease activity measures being significantly more stringent. The prevalence of ID was affected by concomitant fibromyalgia, decreased spine mobility and concomitant NSAIDs.
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Affiliation(s)
- Sara Monti
- a Department of Rheumatology , University of Pavia, IRCCS Policlinico S. Matteo Foundation , Pavia , Italy
| | - Monica Todoerti
- a Department of Rheumatology , University of Pavia, IRCCS Policlinico S. Matteo Foundation , Pavia , Italy
| | - Veronica Codullo
- a Department of Rheumatology , University of Pavia, IRCCS Policlinico S. Matteo Foundation , Pavia , Italy
| | | | | | - Andrea Becciolini
- b Department of Rheumatology , Gaetano Pini Institute , Milan , Italy
| | - Carlomaurizio Montecucco
- a Department of Rheumatology , University of Pavia, IRCCS Policlinico S. Matteo Foundation , Pavia , Italy
| | - Roberto Caporali
- a Department of Rheumatology , University of Pavia, IRCCS Policlinico S. Matteo Foundation , Pavia , Italy
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Wendling D, Guillot X, Gossec L, Prati C, Saraux A, Dougados M. Remission is related to CRP and smoking in early axial spondyloarthritis. The DESIR cohort. Joint Bone Spine 2017; 84:473-476. [DOI: 10.1016/j.jbspin.2016.06.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Accepted: 06/15/2016] [Indexed: 01/20/2023]
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20
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[Treat-to-target (T2T) recommendation for patients with spondyloarthritis - translation into German]. Z Rheumatol 2016; 75:903-909. [PMID: 27488447 DOI: 10.1007/s00393-016-0124-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
The management of patients with spondyloarthritis (SpA) has experienced a paradigm shift in recent years. This is true for the treatment of axial as well as peripheral manifestations. International treat to target (T2T) recommendations for SpA based on the T2T strategy have now also been published, which contain 5 higher level principles (A-E) in addition to the 15 recommendations. In order to make the recommendations known and to promote national distribution, German experts have now issued a translation of the T2T recommendations for SpA into German.
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Wendling D, Prati C. Remission in axial spondyloarthritis: The ultimate treatment goal? Joint Bone Spine 2016; 83:117-9. [DOI: 10.1016/j.jbspin.2015.08.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2015] [Indexed: 01/15/2023]
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22
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Wendling D. Treating to target in axial spondyloarthritis: defining the target and the arrow. Expert Rev Clin Immunol 2015; 11:691-3. [DOI: 10.1586/1744666x.2015.1039514] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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23
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GODFRIN-VALNET MARIE, PUYRAVEAU MARC, WENDLING DANIEL. Remission Thresholds in Spondyloarthritis: A Prospective Study in Current Practice. J Rheumatol 2014; 41:617-8. [DOI: 10.3899/jrheum.131092] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Tins BJ, Butler R. Imaging in rheumatology: reconciling radiology and rheumatology. Insights Imaging 2013; 4:799-810. [PMID: 24127271 PMCID: PMC3846932 DOI: 10.1007/s13244-013-0293-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2013] [Revised: 09/17/2013] [Accepted: 09/19/2013] [Indexed: 02/07/2023] Open
Abstract
Imaging in rheumatology was in the past largely confined to radiographs of the hands and sacroiliac joints (SIJs) helping to establish the diagnosis and then monitoring disease progression. Radiographs are not very sensitive for early inflammation in inflammatory rheumatic disorders and the demand on imaging services was therefore limited. However, over the last 10-15 years new drugs and new technologies have brought new challenges and opportunities to rheumatology and radiology as specialties. New drug treatments allow more effective treatment, preventing many complications. Early diagnosis and disease monitoring has become the challenge for the rheumatologist and radiologist alike. The best possible patient outcome is only achieved if the two specialties understand each other's viewpoint. This article reviews the role of imaging-in particular radiography, magnet resonance imaging, computer tomography, ultrasound and nuclear medicine-for the diagnosis and monitoring of rheumatological disorders, concentrating on rheumatoid arthritis, inflammatory spondylarthropathies and gout. Teaching Points • New drugs for the treatment of inflammatory disorders has led to greatly improved outcomes. • Imaging often allows for earlier diagnosis of inflammatory disorders. • Early diagnosis and treatment can often prevent the development of crippling disease manifestations. • Tailored imaging examinations are best achieved by consultation of rheumatologist and radiologist.
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Affiliation(s)
- Bernhard J Tins
- Robert Jones and Agnes Hunt Orthopaedic Hospital, NHS Trust, Twmpath Lane, Oswestry, SY10 7AG, UK,
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Evaluation of spondylarthritis activity by patients and physicians: ASDAS, BASDAI, PASS, and flares in 200 patients. Joint Bone Spine 2013; 80:393-8. [PMID: 23453478 DOI: 10.1016/j.jbspin.2013.01.003] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2012] [Indexed: 01/26/2023]
Abstract
OBJECTIVES In patients with spondyloarthritis, to determine Ankylosing Spondylitis Disease Activity Score (ASDAS) cutoffs matching the patient-acceptable symptom state (PASS) and patient-reported levels of disease activity, to assess associations between disease activity levels and presence of depression, and to identify ASDAS and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) cutoffs indicating a flare and indicating a remission. METHODS Prospective single-center study of patients meeting ASAS criteria for spondyloarthritis receiving follow-up at the Besançon teaching hospital, France, between February 2011 and February 2012. In each patient, the BASDAI, ASDAS, Bath Ankylosing Spondylitis Functional Index (BASFI), patient-acceptable symptom state (PASS) and signs of depression were assessed. Receiver-operating characteristic (ROC) curves were drawn to identify the ASDAS cutoffs separating different levels of disease activity. The kappa coefficient was computed to evaluate agreement between patients and physicians regarding the presence of flares. RESULTS Two hundred patients with a mean age of 44.4 ± 12.5 years and mean disease duration of 12.9 ± 10.5 years were included. Mean BASDAI was 4.1 ± 2.2, mean ASDAS-C-reactive protein (CRP) was 2.4 ± 1, mean BASFI was 3.3 ± 2.7, and 58.9% of patients reported being in the PASS. The PASS was associated with BASDAI values inferior or equal to 4.1 and ASDAS-CRP values inferior or equal to 2.3. Mild patient-reported disease activity was associated with BASDAI values inferior or equal to 3.8 and ASDAS-CRP values inferior or equal to 2.3; corresponding values for high patient-reported disease activity were superior to 5.2 and superior to 3.1. Among patients reporting high disease activity, 64.5% had Beck Depression Inventory scores consistent with severe depression. At the time of the visit, 36.9% of the patients and 28.3% of the physicians felt there was a flare. Cutoffs indicating a flare were superior or equal to 5.2 for the BASDAI and superior or equal to 2.3 for the ASDAS-CRP. Agreement between patients and physicians regarding flares was good (Kappa, 0.61). An evaluation in 43 patients indicated that an ASDAS-CRP cutoff inferior or equal to 2.2 separated the 25.6% of patients who reported being in remission from the other patients. CONCLUSION Our results show a significant association between disease activity and depression severity, as well as good agreement between BASDAI and ASDAS. The ASDAS cutoffs for the various levels of patient-reported disease activity differed from the cutoffs suggested by ASAS; a 2.3 cutoff was found for both patient-reported absence of disease activity and PASS, indicating that achieving PASS should be included among our treatment objectives.
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