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Nicola Dalbeth - One of the best experts on this subject based on the ideXlab platform.
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relationship of bone erosion with the urate and soft tissue components of the Tophus in gout a dual energy computed tomography study
Rheumatology, 2017Co-Authors: Mark Sapsford, Greg D Gamble, Anthony Doyle, Opetaia Aati, Julie Knight, Anne Horne, Nicola DalbethAbstract:OBJECTIVES Imaging and pathology studies have established a close relationship between Tophus and bone erosion in gout. The Tophus is an organized structure consisting of urate crystals and chronic inflammatory tissue. The aim of this work was to examine the relationship between bone erosion and each component of the Tophus. METHODS Plain radiographs and dual energy CT scans of the feet were prospectively obtained from 92 people with tophaceous gout. The 10 MTP joints were scored for erosion score, Tophus urate and soft tissue volume. Data were analysed using generalized estimating equations and mediation analysis. RESULTS Tophus was visualized in 80.2% of all joints with radiographic (XR) erosion [odds ratio (OR) = 7.1 (95% CI: 4.8, 10.6)] and urate was visualized in 78.6% of all joints with XR erosion [OR = 6.6 (95% CI: 4.7, 9.3)]. In mediation analysis, Tophus urate volume and soft tissue volume were directly associated with XR erosion score. About a third of the association of the Tophus urate volume with XR erosion score was indirectly mediated through the strong association between Tophus urate volume and Tophus soft tissue volume. CONCLUSION Urate and soft tissue components of the Tophus are strongly and independently associated with bone erosion in gout.
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Additional file 1: of Population-specific association between ABCG2 variants and tophaceous disease in people with gout
2017Co-Authors: Amanda Phipps-green, Lisa Stamp, Tony Merriman, Nicola DalbethAbstract:Full SLC2A9 and ABCG2 genotype distributions according to Tophus status. (PDF 42 kb
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Tophus resolution with pegloticase a prospective dual energy ct study
RMD Open, 2015Co-Authors: Elizabeth G Araujo, Sara Bayat, Matthias Englbrecht, Alexander Cavallaro, Michael Lell, Christina Petsch, Francesca Faustini, Arnd Kleyer, Axel J Hueber, Nicola DalbethAbstract:Objective To investigate the effect of intensive lowering of serum uric acid (SUA) levels by pegloticase on the resolution of tophi in patients with refractory gout. Methods Descriptive study in patients with refractory gout receiving pegloticase treatment. SUA levels were measured before and after each infusion. Dual-energy CT (DECT) scans were taken from all patients before the first infusion and after the last infusion. Computerised Tophus volumes were calculated for the baseline and follow-up assessments and compared with each other. Results 10 patients with refractory gout and baseline mean SUA level of 8.1 mg/dL were enrolled. Patients were treated for a mean of 13.3 weeks. Pegloticase effectively reduced tophi in all patients showing a decrease in volume by 71.4%. Responders, showing reduction of SUA level below 6 mg/dL during at least 80% of the treatment time, were virtually cleared from tophi (−94.8%). Dependent on their anatomical localisation, resolution of tophi showed different dynamics, with articular tophi showing fast, and tendon tophi slow, resolution. Conclusions Tophi are highly sensitive to pegloticase treatment, particularly when located at articular sites. Debulking of disease and a Tophus-free state can be reached within a few months of pegloticase treatment. DECT allows for comprehensively assessing Tophus burden and monitoring treatment responses.
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development of a patient reported outcome measure of Tophus burden the Tophus impact questionnaire tiq 20
Annals of the Rheumatic Diseases, 2014Co-Authors: Opetaia Aati, Anne Horne, Lisa K Stamp, William J Taylor, Richard J Siegert, Meaghan E House, Paul Tan, Jill Drake, Nicola DalbethAbstract:Background Tophus burden is currently measured using physical examination and imaging methods. The aim of this study was to develop a patient-reported outcome (PRO) tool to assess Tophus burden in people with gout. Methods The responses from interviews with 25 people with tophaceous gout were used to generate items for a preliminary PRO tool. Following cognitive testing of each item, a preliminary 34-item questionnaire was administered to 103 people with tophaceous gout. Rasch analysis generated a 20-item Tophus Impact Questionnaire (TIQ-20). Test-retest reproducibility and construct validity of the TIQ-20 were assessed. Results The TIQ-20 responses fit the Rasch model and demonstrated unidimensionality, adequate precision, absence of differential item functioning and adequate person separation index. The TIQ-20 included items related to pain, activity limitation, footwear modification, participation, psychological impact and healthcare use due to tophi. In the 103 patients with tophaceous gout, floor effects were observed in 4.9% and ceiling effects in 1%. The TIQ-20 test-retest intraclass correlation coefficient was 0.76 (95% CI 0.61 to 0.85). All predicted correlations for construct validity testing were observed, including weak correlation with serum urate concentrations (r 0.50). Conclusions We have developed a Tophus-specific PRO in patients with tophaceous gout. The TIQ-20 demonstrates acceptable psychometric properties. Initial results show internal, face and construct validity, reproducibility and feasibility. Further research is required to determine responsiveness to change.
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characterization of new bone formation in gout a quantitative site by site analysis using plain radiography and computed tomography
Arthritis Research & Therapy, 2012Co-Authors: Nicola Dalbeth, Barnaby Clark, Anthony Doyle, Aaron Milligan, Fiona M McqueenAbstract:Introduction: Radiographic descriptions of gout have noted the tendency to hypertrophic bone changes. The aim of this study was to characterize the features of new bone formation (NBF) in gout, and to determine the relationship between NBF and other radiographic features of disease, particularly erosion and Tophus. Methods: Paired plain radiographs (XR) and computed tomography (CT) scans of 798 individual hand and wrist joints from 20 patients with gout were analyzed. Following a structured review of a separate set of images, films were scored for the presence of the following features of NBF: spur, osteophyte, periosteal NBF, ankylosis and sclerosis. The relationship between NBF and other radiographic features was analyzed. Results: The most frequent forms of NBF were bone sclerosis and osteophyte. Spur and periosteal NBF were less common, and ankylosis was rare. On both XR and CT, joints with bone erosion were more likely to have NBF; for CT, if erosion was present, the odds ratios (OR) was 45.1 for spur, 3.3 for osteophyte, 16.6 for periosteal NBF, 26.6 for ankylosis and 32.3 for sclerosis, P for all < 0.01. Similarly, on CT, joints with intraosseous Tophus were more likely to have NBF; if Tophus was present, the OR was 48.4 for spur, 3.3 for osteophyte, 14.5 for periosteal NBF, 35.1 for ankylosis and 39.1 for sclerosis; P for all < 0.001. Conclusions: This detailed quantitative analysis has demonstrated that NBF occurs more frequently in joints affected by other features of gout. This work suggests a connection between bone loss, Tophus, and formation of new bone during the process of joint remodelling in gout.
Ya-ting Chang - One of the best experts on this subject based on the ideXlab platform.
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Characteristics of scrub typhus, murine typhus, and Q fever among elderly patients: Prolonged prothrombin time as a predictor for severity
Elsevier, 2019Co-Authors: Ko Chang, Nan-yao Lee, Wei-ru Lin, Yen-hsu Chen, Jih-jin Tsai, Tun-chieh Chen, Chun-yu Lin, Ya-ting ChangAbstract:Background/purpose: The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear. Methods: We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18–64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002–2011. Results: Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01–0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33–9.99). Conclusion: The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications. Keywords: Elderly, Scrub typhus, Acute Q fever, Murine typhus, Complication
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characteristics of scrub typhus murine typhus and q fever among elderly patients prolonged prothrombin time as a predictor for severity
Journal of Microbiology Immunology and Infection, 2017Co-Authors: Ko Chang, Nan-yao Lee, Wei-ru Lin, Yen-hsu Chen, Jih-jin Tsai, Tun-chieh Chen, Chun-yu Lin, Ya-ting ChangAbstract:Abstract Background/purpose The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear. Methods We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18–64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002–2011. Results Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly ( p = 0.022), dyspnea ( p = 0.006), less relative bradycardia ( p = 0.004), less febrile illness ( p = 0.004), prolonged prothrombin time (PT) ( p = 0.002), higher levels of initial C-reactive protein ( p = 0.039), blood leukocyte counts ( p = 0.01), and lower platelet counts ( p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis ( p = 0.018, CI 95% 0.01–0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly ( p = 0.012, 95% confidence interval [CI]: 1.33–9.99). Conclusion The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications.
Fiona M Mcqueen - One of the best experts on this subject based on the ideXlab platform.
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path analysis identifies receptor activator of nuclear factor κb ligand osteoprotegerin and sclerostin as potential mediators of the Tophus bone erosion relationship in gout
The Journal of Rheumatology, 2016Co-Authors: Ashika Chhana, Karen E Callon, Fiona M Mcqueen, Anthony Doyle, Opetaia Aati, Anne Horne, Gregory D Gamble, Mark Roger, Ian R Reid, Jillian CornishAbstract:Objective. To determine the relationship between Tophus, erosion and bone remodeling factors in gout. Methods. Computed tomography bone erosion and circulating bone factors were measured in adults with tophaceous gout. Multiple regression modeling and path analysis were used to determine predictors of erosion. Results. Tophus number, Māori or Pacific ethnicity, creatinine, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin were independently associated with erosion. Path analysis showed a direct effect of Tophus number on erosion, partially mediated through OPG, RANKL, and sclerostin. Conclusion. Tophus number is strongly associated with bone erosion in gout. Circulating RANKL, OPG, and sclerostin are potential mediators of Tophus-related erosion.
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characterization of new bone formation in gout a quantitative site by site analysis using plain radiography and computed tomography
Arthritis Research & Therapy, 2012Co-Authors: Nicola Dalbeth, Barnaby Clark, Anthony Doyle, Aaron Milligan, Fiona M McqueenAbstract:Introduction: Radiographic descriptions of gout have noted the tendency to hypertrophic bone changes. The aim of this study was to characterize the features of new bone formation (NBF) in gout, and to determine the relationship between NBF and other radiographic features of disease, particularly erosion and Tophus. Methods: Paired plain radiographs (XR) and computed tomography (CT) scans of 798 individual hand and wrist joints from 20 patients with gout were analyzed. Following a structured review of a separate set of images, films were scored for the presence of the following features of NBF: spur, osteophyte, periosteal NBF, ankylosis and sclerosis. The relationship between NBF and other radiographic features was analyzed. Results: The most frequent forms of NBF were bone sclerosis and osteophyte. Spur and periosteal NBF were less common, and ankylosis was rare. On both XR and CT, joints with bone erosion were more likely to have NBF; for CT, if erosion was present, the odds ratios (OR) was 45.1 for spur, 3.3 for osteophyte, 16.6 for periosteal NBF, 26.6 for ankylosis and 32.3 for sclerosis, P for all < 0.01. Similarly, on CT, joints with intraosseous Tophus were more likely to have NBF; if Tophus was present, the OR was 48.4 for spur, 3.3 for osteophyte, 14.5 for periosteal NBF, 35.1 for ankylosis and 39.1 for sclerosis; P for all < 0.001. Conclusions: This detailed quantitative analysis has demonstrated that NBF occurs more frequently in joints affected by other features of gout. This work suggests a connection between bone loss, Tophus, and formation of new bone during the process of joint remodelling in gout.
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Tophus measurement as an outcome measure for clinical trials of chronic gout progress and research priorities
The Journal of Rheumatology, 2011Co-Authors: Nicola Dalbeth, Fiona M Mcqueen, J B Singh, Patricia A Macdonald, Lawrence N Edwards, Ralph H Schumacher, Lee S Simon, Lisa K Stamp, Tuhina Neogi, Angelo L GaffoAbstract:Despite the recognition that Tophus regression is an important outcome measure in clinical trials of chronic gout, there is no agreed upon method of Tophus measurement. A number of methods have been used in clinical trials of chronic gout, from simple physical measurement techniques to more complex advanced imaging methods. This article summarizes methods of Tophus measurement and discusses their properties. Physical measurement using Vernier calipers meets most aspects of the Outcome Measures in Rheumatology (OMERACT) filter. Rigorous testing of the complex methods, particularly with respect to reliability and sensitivity to change, is needed to determine the appropriate use of these methods. Further information is also required regarding which method of physical measurement is best for use in future clinical trials. The need to develop and test a patient-reported outcome measure of Tophus burden is also highlighted.
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methods of Tophus assessment in clinical trials of chronic gout a systematic literature review and pictorial reference guide
Annals of the Rheumatic Diseases, 2011Co-Authors: Nicola Dalbeth, Hyon K Choi, Fiona M Mcqueen, Anthony Doyle, Patricia A Macdonald, Ralph H Schumacher, Cameron Schauer, Fernando Perezruiz, Steve Hamburger, William J TaylorAbstract:Objective To identify methods of Tophus measurement for gout studies, summarise the properties of these methods and compile a detailed pictorial reference guide to demonstrate the methods. Methods A systematic search strategy for methods of Tophus measurement was formulated. For each method, papers were assessed by two reviewers to summarise information according to the specific components of the Outcomes Measures in Rheumatology (OMERACT) filter: feasibility, truth and discrimination. Detailed images were obtained to construct the reference guide. Results Eight methods of Tophus measurement were identified: counting the total number of tophi, physical measurement using tape measure, physical measurement using Vernier callipers, digital photography, ultrasonography (US), MRI, CT and dual energy CT. Feasibility aspects of the methods are well documented. Physical measurement techniques are more feasible than advanced imaging methods, but do not allow for assessment of intra-articular tophi or for data storage and central reading. The truth aspect of the filter has been documented for many methods, particularly Vernier callipers, US, MRI and CT. Reliability of most methods has been reported as very good or excellent. Sensitivity to change has been reported for all methods except MRI and CT. Conclusion A variety of methods of Tophus assessment have been described for use in clinical trials of chronic gout. Physical measurement techniques (particularly the Vernier calliper method) and US measurement of Tophus size appear to meet most aspects of the OMERACT filter.
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cellular characterization of the gouty Tophus a quantitative analysis
Arthritis & Rheumatism, 2010Co-Authors: Nicola Dalbeth, Bregina Pool, Greg D Gamble, Timothy M Smith, Karen E Callon, Fiona M Mcqueen, Jillian CornishAbstract:Objective To characterize the cellular architecture of the Tophus and to determine the presence of cytokines implicated in the initiation and resolution of gouty inflammation. Methods Sixteen fixed, paraffin-embedded, uninfected Tophus samples were surgically obtained from 12 patients with microscopically proven gout and were analyzed by quantitative immunohistochemistry. The number of cells present in the corona and fibrovascular zones of the Tophus was analyzed by Genmod mixed models analysis. Results Numerous CD68+ mononucleated and multinucleated cells were present within the corona zone. Mast cells were identified in all Tophus samples and at similar densities throughout the corona and fibrovascular zones. In contrast, neutrophils were rarely observed. Plasma cells were present in very high numbers within the corona zone. The overall number of CD20+ B cells was much lower. However, in 6 of 12 patients (50%), at least 1 B cell aggregate was present in the fibrovascular zone. Large numbers of cells expressing interleukin-1β (IL-1β) were observed in the corona zone. Transforming growth factor β1 (TGFβ1)–expressing mononucleated cells were also identified. The number of CD68+ cells correlated with the number of cells expressing IL-1β (r = 0.691, P = 0.009) and the number expressing TGFβ1 (r = 0.518, P = 0.04). Conclusion The Tophus represents a complex and organized chronic inflammatory tissue response to monosodium urate monohydrate crystals involving both innate and adaptive immune cells. The coexpression of IL-1β and TGFβ1 suggests that both proinflammatory and antiinflammatory factors present within the Tophus contribute to a cycle of chronic inflammation, attempted resolution, and tissue remodeling.
Anthony Doyle - One of the best experts on this subject based on the ideXlab platform.
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relationship of bone erosion with the urate and soft tissue components of the Tophus in gout a dual energy computed tomography study
Rheumatology, 2017Co-Authors: Mark Sapsford, Greg D Gamble, Anthony Doyle, Opetaia Aati, Julie Knight, Anne Horne, Nicola DalbethAbstract:OBJECTIVES Imaging and pathology studies have established a close relationship between Tophus and bone erosion in gout. The Tophus is an organized structure consisting of urate crystals and chronic inflammatory tissue. The aim of this work was to examine the relationship between bone erosion and each component of the Tophus. METHODS Plain radiographs and dual energy CT scans of the feet were prospectively obtained from 92 people with tophaceous gout. The 10 MTP joints were scored for erosion score, Tophus urate and soft tissue volume. Data were analysed using generalized estimating equations and mediation analysis. RESULTS Tophus was visualized in 80.2% of all joints with radiographic (XR) erosion [odds ratio (OR) = 7.1 (95% CI: 4.8, 10.6)] and urate was visualized in 78.6% of all joints with XR erosion [OR = 6.6 (95% CI: 4.7, 9.3)]. In mediation analysis, Tophus urate volume and soft tissue volume were directly associated with XR erosion score. About a third of the association of the Tophus urate volume with XR erosion score was indirectly mediated through the strong association between Tophus urate volume and Tophus soft tissue volume. CONCLUSION Urate and soft tissue components of the Tophus are strongly and independently associated with bone erosion in gout.
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path analysis identifies receptor activator of nuclear factor κb ligand osteoprotegerin and sclerostin as potential mediators of the Tophus bone erosion relationship in gout
The Journal of Rheumatology, 2016Co-Authors: Ashika Chhana, Karen E Callon, Fiona M Mcqueen, Anthony Doyle, Opetaia Aati, Anne Horne, Gregory D Gamble, Mark Roger, Ian R Reid, Jillian CornishAbstract:Objective. To determine the relationship between Tophus, erosion and bone remodeling factors in gout. Methods. Computed tomography bone erosion and circulating bone factors were measured in adults with tophaceous gout. Multiple regression modeling and path analysis were used to determine predictors of erosion. Results. Tophus number, Māori or Pacific ethnicity, creatinine, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin were independently associated with erosion. Path analysis showed a direct effect of Tophus number on erosion, partially mediated through OPG, RANKL, and sclerostin. Conclusion. Tophus number is strongly associated with bone erosion in gout. Circulating RANKL, OPG, and sclerostin are potential mediators of Tophus-related erosion.
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characterization of new bone formation in gout a quantitative site by site analysis using plain radiography and computed tomography
Arthritis Research & Therapy, 2012Co-Authors: Nicola Dalbeth, Barnaby Clark, Anthony Doyle, Aaron Milligan, Fiona M McqueenAbstract:Introduction: Radiographic descriptions of gout have noted the tendency to hypertrophic bone changes. The aim of this study was to characterize the features of new bone formation (NBF) in gout, and to determine the relationship between NBF and other radiographic features of disease, particularly erosion and Tophus. Methods: Paired plain radiographs (XR) and computed tomography (CT) scans of 798 individual hand and wrist joints from 20 patients with gout were analyzed. Following a structured review of a separate set of images, films were scored for the presence of the following features of NBF: spur, osteophyte, periosteal NBF, ankylosis and sclerosis. The relationship between NBF and other radiographic features was analyzed. Results: The most frequent forms of NBF were bone sclerosis and osteophyte. Spur and periosteal NBF were less common, and ankylosis was rare. On both XR and CT, joints with bone erosion were more likely to have NBF; for CT, if erosion was present, the odds ratios (OR) was 45.1 for spur, 3.3 for osteophyte, 16.6 for periosteal NBF, 26.6 for ankylosis and 32.3 for sclerosis, P for all < 0.01. Similarly, on CT, joints with intraosseous Tophus were more likely to have NBF; if Tophus was present, the OR was 48.4 for spur, 3.3 for osteophyte, 14.5 for periosteal NBF, 35.1 for ankylosis and 39.1 for sclerosis; P for all < 0.001. Conclusions: This detailed quantitative analysis has demonstrated that NBF occurs more frequently in joints affected by other features of gout. This work suggests a connection between bone loss, Tophus, and formation of new bone during the process of joint remodelling in gout.
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methods of Tophus assessment in clinical trials of chronic gout a systematic literature review and pictorial reference guide
Annals of the Rheumatic Diseases, 2011Co-Authors: Nicola Dalbeth, Hyon K Choi, Fiona M Mcqueen, Anthony Doyle, Patricia A Macdonald, Ralph H Schumacher, Cameron Schauer, Fernando Perezruiz, Steve Hamburger, William J TaylorAbstract:Objective To identify methods of Tophus measurement for gout studies, summarise the properties of these methods and compile a detailed pictorial reference guide to demonstrate the methods. Methods A systematic search strategy for methods of Tophus measurement was formulated. For each method, papers were assessed by two reviewers to summarise information according to the specific components of the Outcomes Measures in Rheumatology (OMERACT) filter: feasibility, truth and discrimination. Detailed images were obtained to construct the reference guide. Results Eight methods of Tophus measurement were identified: counting the total number of tophi, physical measurement using tape measure, physical measurement using Vernier callipers, digital photography, ultrasonography (US), MRI, CT and dual energy CT. Feasibility aspects of the methods are well documented. Physical measurement techniques are more feasible than advanced imaging methods, but do not allow for assessment of intra-articular tophi or for data storage and central reading. The truth aspect of the filter has been documented for many methods, particularly Vernier callipers, US, MRI and CT. Reliability of most methods has been reported as very good or excellent. Sensitivity to change has been reported for all methods except MRI and CT. Conclusion A variety of methods of Tophus assessment have been described for use in clinical trials of chronic gout. Physical measurement techniques (particularly the Vernier calliper method) and US measurement of Tophus size appear to meet most aspects of the OMERACT filter.
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mechanisms of bone erosion in gout a quantitative analysis using plain radiography and computed tomography
Annals of the Rheumatic Diseases, 2009Co-Authors: Nicola Dalbeth, Greg D Gamble, Barnaby Clark, Kate Gregory, Timothy Sheehan, Anthony Doyle, Fiona M McqueenAbstract:Objective: The underlying basis of bone erosion in gout remains speculative. The aim of this study was to understand the mechanisms of bone erosion in gout using non-invasive imaging techniques. Methods: Paired plain radiographs and computed tomography (CT) scans of 798 individual hand and wrist joints from 20 patients with gout were analysed. Radiographs were scored for erosion (0–5) using the Sharp/van der Heijde method. CT scans were scored for the presence and diameter of bone erosions and tophi. The presence of intraosseous Tophus (Tophus visualised within bone) was recorded. The relationships between radiographic erosion, CT erosion and Tophus scores were analysed. Results: With increasing radiographic erosion scores, the percentage of joints with intraosseous Tophus increased (p Conclusion: There is a strong relationship between bone erosion and the presence of intraosseous Tophus. These results strongly implicate Tophus infiltration into bone as the dominant mechanism for the development of bone erosion and joint damage in gout.
Brian F Mandell - One of the best experts on this subject based on the ideXlab platform.
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Tophus resolution in patients with chronic refractory gout who have persistent urate lowering responses to pegloticase
Arthritis Research & Therapy, 2018Co-Authors: Brian F Mandell, Anthony E Yeo, Peter E LipskyAbstract:Pegloticase is a recombinant mammalian uricase conjugated to polyethylene glycol approved in the United States for treatment of chronic refractory gout. It can profoundly decrease serum urate to < 1 mg/dl. In patients receiving pegloticase who did not generate high-titer antidrug antibodies (responders), the serum urate remained low for the duration of therapy, 6 months in the phase III clinical trials plus the open-label extension. The objective of this study was to assess the velocity of Tophus resolution in subjects treated with pegloticase. Data from two randomized controlled trials of pegloticase in chronic refractory gout were analyzed. Tophi were assessed by computer-assisted measurements of standardized digital photographs. Subjects were designated as responders and nonresponders based on maintenance of serum urate < 6 mg/dl at months 3 and 6 of treatment. The projected time of complete resolution of all tophi was determined by linear regression analysis. The mean total Tophus area at baseline was 585.8 mm2 for responders, 661.5 mm2 for nonresponders, and 674.4 mm2 for placebo-treated patients. Complete resolution at 6 months of at least one Tophus was achieved by 69.6% of 23 responders, 27.9% of 43 nonresponders, and 14.3% of 21 patients who received placebo. Complete resolution of all photographed tophi was achieved by 34.8% of biochemical responders, 11.6% of nonresponders, and 0% of placebo-treated patients. The mean velocity of resolution of all tophi was 60.1 mm2/month in responders with a mean projected time of complete resolution of 9.9 months (4.6–32.6 months). There was a significant inverse correlation between serum urate AUC and Tophus resolution velocity (r = − 0.40, P = 0.0002), although considerable heterogeneity in the velocity of resolution was noted. The only patient characteristic that correlated with the velocity of Tophus resolution was the baseline Tophus area. Pegloticase treatment caused a rapid resolution of tophi in responders that correlated with the serum urate lowering associated with this therapy.
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sat0356 factors influencing Tophus resolution in patients with persistent urate lowering responses to pegloticase
Annals of the Rheumatic Diseases, 2018Co-Authors: Brian F Mandell, Anthony E Yeo, P LipskyAbstract:Background Pegloticase is a recombinant mammalian uricase conjugated to polyethylene glycol approved for treatment of chronic refractory gout. It profoundly decreases serum urate levels and also causes rapid resolution of tophi. However, there is considerable heterogeneity in the velocity of Tophus resolution. Objectives To assess factors that may influence the velocity of Tophus resolution in subjects with persistent lowering of serum urate levels. Methods This analysis used results from two randomised controlled trials (RCT) of 6 months duration.1,2 Tophus assessment was carried out using Computer-Assisted Photographic Evaluation in Rheumatology (CAPER) methodology.3 Photographs of hands and feet and two other area of visually apparent tophi were taken and assessed for total Tophus area and also resolution of tophi in response to therapy. Subjects were defined as responders based upon maintenance of serum urate 1690 mm2), and the velocity of Tophus resolution was determined for each of these groups. Results The mean measured total Tophus area at baseline was 585.8 mm2 for biochemical responders and complete resolution of all tophi photographed was achieved by 34.8% of this group during the RCT. The velocity of Tophus resolution for the pegloticase responders was 60.1 mm2 per month. Clinical features including, age, body mass index, gender, race, and Tophus location did not significantly influence the velocity of Tophus resolution. The mean (standard deviation [SD]) baseline Tophus areas at baseline were 419.4 mm2 (202.4) for subjects with low baseline Tophus burden, 1176.9 mm2 (238.7) for those with moderate Tophus burden, and 4260.4 mm2 (2784.9) for those with high baseline Tophus burden. The mean (SD) velocity of Tophus resolution was 28.7 mm2/month (13.6) for patients with low baseline Tophus burden, 60.2 mm2/month (53.5) for those with moderate baseline Tophus burden, and 89.5 mm2/month (38.7) for those with high baseline Tophus burden. Even though the velocity of resolution was greater for those with a larger Tophus burden, the time required for complete Tophus resolution was substantially less for those with a smaller Tophus burden. The projected times to resolution of all visualised tophi determined by linear regression analysis were 6.98, 7.14 and 12.02 months for the subjects with low, medium and high baseline Tophus burden (p Conclusions Pegloticase treatment causes a rapid resolution of tophi in biochemical responders and the rate of decrease is not significantly associated with age, body mass index, gender, race, or Tophus location. However, the rate of Tophus resolution is inversely correlated with the total Tophus burden at the beginning of treatment. References [1] Sundy JS, et al. JAMA2011;306:711–720. [2] Becker MA, et al. Ann Rheum Dis2013;72:1469–1474. [3] Maroli AN, et al. Arthritis Rheum2009;60:1111. Disclosure of Interest B. Mandell Grant/research support from: Horizon Pharma, Consultant for: Horizon Pharma, Ironwood, A. Yeo Consultant for: Horizon Pharma, P. Lipsky Consultant for: Horizon Pharma
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thu0416 rapid Tophus resolution in chronic refractory gout patients treated with pegloticase
Annals of the Rheumatic Diseases, 2017Co-Authors: Brian F Mandell, Anthony E Yeo, P LipskyAbstract:Background It has been suggested that the velocity of resolution of tophi in persons with chronic tophaceous gout is related to the serum urate levels.1 However, few subjects with a persistent serum urate less than 4.0 mg/dL were studied. Pegloticase is a recombinant uricase conjugated to polyethylene glycol approved in the US for treatment of patients with chronic refractory gout. It profoundly decreases serum uric acid in responders to Objectives To assess the velocity of Tophus resolution in subjects treated with pegloticase for chronic refractory gout. Methods This analysis used results from two randomized controlled trials (RCTs) of 6 months duration.2,3 For Tophus measurements, serial standardized digital photographs were analyzed by a blinded reader using computer-assisted quantitative measurement software. Subjects were defined as responders and nonresponders based upon maintenance of a serum urate Results During the 6 months of the RCTs, a total of 952 Tophus measurements were analyzed in 87 subjects, including 341 in 30 responders; 361 in 36 nonresponders receiving pegloticase infusions; and 250 in 21 subjects receiving placebo infusions. Mean serum urate levels in these subjects were 10.1, 0.3 and 0.3 mg/dL at baseline, 3 months and 6 months in responders; 10.7, 8.9 and 9.6 mg/dL in nonresponders; and 10.2, 9.8 and 9.7 mg/dL in placebo treated patients, respectively. At baseline, the mean Tophus area in responders was 581.6 +/- 742.7 mm2 (mean ± SD; n=90 tophi); in nonresponders it was 676.5+/-1416.6 mm2 (n=93 tophi); and in placebo treated subjects it was 672.9+/-1039.5 mm2 (n=66 tophi). By regression analysis, the velocity of Tophus resolution over the 6 months of treatment was 50.1 mm2/month in responders; 14.0 mm2/month in nonresponders; and 13.9 mm2/month in placebo treated patients (responders versus nonresponders or responders vs placebo treated subjects (p=0.001)). In responders, the mean time to total Tophus resolution was estimated to be 347 days (11.5 months, with a range of 5.6–36.4 months). During the 6 month treatment period, the area under the curve (AUC) of multiple serum urate measurements in responders was 6,067.9+/-6,781.6 mg/dL hr compared with 34,647.4+/-8,586.7 and 42,451.1+/-6,396.1 mg/dL·hr in nonresponders and placebo treated subjects, respectively (p Conclusions Pegloticase treatment causes a rapid resolution of tophi in responders as predicted from the profound and persistent serum urate lowering associated with this therapy. References Perez-Ruiz F et al, Arthritis Rheum 2002; 47:356–60. Sundy JS, et al. JAMA. 2011;306:711–720. Becker MA, et al. Ann Rheum Dis. 2013;72:1469–1474. Disclosure of Interest B. Mandell Grant/research support from: Horizon, Consultant for: Horizon, Ironwood, A. Yeo Consultant for: Horizon Pharma, P. Lipsky Consultant for: AstraZeneca, Celgene, EMD Serono, GSK, Horizon Pharma, Janssen, Medimmune, Pfizer, Roche, Sanofi, UCB
