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Jurgen Braun - One of the best experts on this subject based on the ideXlab platform.
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successful treatment of active ankylosing spondylitis with the anti tumor necrosis factor α monoclonal antibody infliximab
Arthritis & Rheumatism, 2000Co-Authors: Jan Brandt, J Sieper, Hildrun Haibel, Daniel Cornely, W. Golder, Jaqueline Reddig, Wolfgang Thriene, J A Gonzalez, Jurgen BraunAbstract:Objective Tumor necrosis factor α (TNFα) has been detected in sacroiliac Joint Biopsy specimens from patients with spondylarthropathy. The present open pilot study was undertaken to test the efficacy of the anti-TNFα monoclonal antibody infliximab in the treatment of active ankylosing spondylitis (AS). Methods Eleven patients with AS of short duration (median 5 years, range 0.5–13 years) that had been active for at least 3 months (range 3–72 months) were treated with 3 infusions of infliximab (at weeks 0, 2, and 6), in a dosage of 5 mg/kg. Ten of the 11 patients had elevated C-reactive protein (CRP) levels (>6 mg/liter) before treatment; these elevations were known to have had persisted >1 year in at least 3 patients. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI), pain as measured on a visual analog scale, and the Bath AS Metrology Index (BASMI) were assessed. Quality of life was assessed using the Short Form 36 instrument. Laboratory markers of disease activity, including interleukin-6 (IL-6) levels, were determined. Dynamic magnetic resonance imaging (MRI) of the spine was performed in 5 patients. Results One patient withdrew from the study due to the occurrence of urticarial xanthoma 8 days after the first infusion. At study enrollment, 3 of 5 patients had evidence of spinal inflammation (spondylitis and spondylodiscitis) as detected by MRI; followup MRI 2–6 weeks after the third infusion revealed improvement in 2. Improvement of ≥50% in activity, function, and pain scores was documented in 9 of 10 patients; the median improvement in the BASDAI after 4 weeks was 70% (range 41–94%). This clear-cut benefit lasted for 6 weeks after the third infusion in 8 of 10 patients. The median CRP level decreased from 15.5 mg/liter (range <6–90.8) to normal, and the median IL-6 level from 12.4 mg/liter (range 0–28.4) to normal (<5). There was improvement in all 9 SF-36 concepts; the improvement was significant for 6 concepts. Conclusion These data suggest that anti-TNFα therapy is very effective for several weeks in AS. Whether this therapy, in addition to its antiinflammatory effect, prevents ankylosis remains to be determined.
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Successful treatment of active ankylosing spondylitis with the anti–tumor necrosis factor α monoclonal antibody infliximab
Arthritis and rheumatism, 2000Co-Authors: Jan Brandt, Hildrun Haibel, Daniel Cornely, W. Golder, Jose Gonzalez, Jaqueline Reddig, Wolfgang Thriene, Joachim Sieper, Jurgen BraunAbstract:Objective Tumor necrosis factor α (TNFα) has been detected in sacroiliac Joint Biopsy specimens from patients with spondylarthropathy. The present open pilot study was undertaken to test the efficacy of the anti-TNFα monoclonal antibody infliximab in the treatment of active ankylosing spondylitis (AS). Methods Eleven patients with AS of short duration (median 5 years, range 0.5–13 years) that had been active for at least 3 months (range 3–72 months) were treated with 3 infusions of infliximab (at weeks 0, 2, and 6), in a dosage of 5 mg/kg. Ten of the 11 patients had elevated C-reactive protein (CRP) levels (>6 mg/liter) before treatment; these elevations were known to have had persisted >1 year in at least 3 patients. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI), pain as measured on a visual analog scale, and the Bath AS Metrology Index (BASMI) were assessed. Quality of life was assessed using the Short Form 36 instrument. Laboratory markers of disease activity, including interleukin-6 (IL-6) levels, were determined. Dynamic magnetic resonance imaging (MRI) of the spine was performed in 5 patients. Results One patient withdrew from the study due to the occurrence of urticarial xanthoma 8 days after the first infusion. At study enrollment, 3 of 5 patients had evidence of spinal inflammation (spondylitis and spondylodiscitis) as detected by MRI; followup MRI 2–6 weeks after the third infusion revealed improvement in 2. Improvement of ≥50% in activity, function, and pain scores was documented in 9 of 10 patients; the median improvement in the BASDAI after 4 weeks was 70% (range 41–94%). This clear-cut benefit lasted for 6 weeks after the third infusion in 8 of 10 patients. The median CRP level decreased from 15.5 mg/liter (range
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use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac Joint Biopsy specimens from patients with ankylosing spondylitis
Arthritis & Rheumatism, 1995Co-Authors: Jurgen Braun, Matthias Bollow, Lucia Neure, Eva Seipelt, Fikret Seyrekbasan, H Herbst, U Eggens, A Distler, J SieperAbstract:OBJECTIVE: To investigate mechanisms involved in inflammation and new bone formation in the sacroiliac (SI) Joints of patients with ankylosing spondylitis (AS). PATIENTS AND METHODS: Computed tomography-assisted Biopsy of the SI Joint was performed in 5 patients with AS with a mean disease duration of 4.5 years and radiographic stage 2-3 disease. Immunohistologic studies were performed with the alkaline phosphatase-anti-alkaline phosphatase technique, and cytokine messenger RNA (mRNA) was detected by in situ hybridization. RESULTS: Dense cellular infiltrates with varying amounts of CD3+ cells (mean +/- SD 53.3 +/- 24.1%), CD4+ cells (29.7 +/- 17.6%), CD8+ cells (15.8 +/- 11.4%), CD14+ cells (23.6 +/- 16.9%), CD45RO+ cells (48.4 +/- 23.6%), and CD45RA+ cells (4.5 +/- 2.9%) were found in the synovial portion of the SI Joints of all 5 patients. In these infiltrates a high amount of tumor necrosis factor alpha (TNF alpha) mRNA and, near the site of new bone formation, a lower amount of transforming growth factor beta (TGF beta) mRNA, were detected, while no message for interleukin-1 was found in the 3 patients examined by this technique. CONCLUSION: The presence of T cells and macrophages was demonstrated in cellular infiltrates in the SI Joints of 5 patients with active AS. The finding of abundant TNF alpha message in these Joints could have implications regarding potential immunotherapeutic approaches to this disease. TGF beta might be involved in new bone formation in AS.
Frances Humby - One of the best experts on this subject based on the ideXlab platform.
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OP0217 INVOLVEMENT OF LARGE JointS AT DISEASE PRESENTATION IS ASSOCIATED WITH DIVERSE HISTOPATHOLOGICAL FEATURES AND CLINICAL OUTCOMES IN EARLY RHEUMATOID ARTHRITIS
Annals of the Rheumatic Diseases, 2020Co-Authors: Felice Rivellese, Frances Humby, Rebecca Hands, G. Lliso Ribera, Alessandra Nerviani, E. Sciacca, Giovanni Giorli, Liliane Fossati-jimack, Georgina Thorborn, Myles LewisAbstract:Background: The involvement of large Joints at disease presentation in early Rheumatoid Arthritis (RA) has been associated with severe disease activity. At the same time, the clinical heterogeneity of RA is known to be mirrored by heterogeneity of synovial inflammation, with specific histological patterns (pathotypes) associated with treatment response and disease progression. However, it is not known whether Joint size is associated with specific pathotypes. Objectives: To analyse histopathological features of synovial biopsies from Joints of different sizes and establish the relationship with clinical outcomes in patients with early RA. Methods: 167 patients with early ( Results: The majority of synovial biopsies were performed on medium and small Joints (60.6% and 19.4%) as compared to 21.3% in large Joints (Table 1). At baseline, patients who underwent large Joint Biopsy showed significantly higher levels of inflammation (CRP 27.9±32.4 large, 20.7±26.9 medium, 10.4±9.8 small, p=0.007) and higher HAQ (1.8 ± 0.7 large, 1.4 ± 0.8 medium, 1.2 ±0.9 small, p=0.012), with no differences in DAS28. Significantly higher inflammatory scores and higher proportion of lympho-myeloid pathotype were observed in large Joints (Table 1 and Figure 1). 6 months after treat-to-target treatment with csDMARDs, large Joints patients had significantly higher HAQ and lower response (RR for low disease activity in large vs medium Joints 0.5, 95%CI 0.2-0.9, p=0.03). Finally, differentially expressed genes by RNA-seq showed segregation according to Joint size (Figure 2), with upregulation of genes of the Homeobox transcription factors family in large Joints. Conclusion: Synovial Biopsy of large Joints as the most inflamed Joints at disease presentation identified patients with early RA with specific histopathological features and clinical outcomes. Together with clustering of differentially expressed genes according to Joint size, this suggests that the involvement of different Joint compartments in early RA contributes to disease heterogeneity with potential physiopathological and clinical implications. References: [1]Humby et al Ann Rheum Dis. 2019 Jun;78(6):761-772 [2]Lewis et al Cell Rep. 2019 Aug 27;28(9):2455-2470.e5 [3]Linn-Rasker SP et al Ann Rheum Dis. 2007 May;66(5):646-50 Acknowledgments: PEAC http://www.peac-mrc.mds.qmul.ac.uk MRC grant 36661 & ARUK Grant 20022 F. Rivellese NIHR Fellowship TRF-2018-11-ST2-002 Disclosure of Interests: None declared
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use of ultrasound guided small Joint Biopsy to evaluate the histopathologic response to rheumatoid arthritis therapy recommendations for application to clinical trials
Arthritis & Rheumatism, 2015Co-Authors: Frances Humby, Stephen Kelly, Rebecca Hands, V. Rocher, Maria Dicicco, Lu Zou, Serena Bugatti, Antonio Manzo, Roberto Caporali, Carlomaurizio MontecuccoAbstract:Medical Research Council to develop the Pathobiology of Early Arthritis Cohort. Grant Number: 86661. The Clinical and Pathological Response to Certolizumab Pegol (CLiPCert). UCB.
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Use of Ultrasound‐Guided Small Joint Biopsy to Evaluate the Histopathologic Response to Rheumatoid Arthritis Therapy: Recommendations for Application to Clinical Trials
Arthritis & rheumatology (Hoboken N.J.), 2015Co-Authors: Frances Humby, Stephen Kelly, Rebecca Hands, V. Rocher, Maria Dicicco, Lu Zou, Serena Bugatti, Antonio Manzo, Roberto CaporaliAbstract:Medical Research Council to develop the Pathobiology of Early Arthritis Cohort. Grant Number: 86661. The Clinical and Pathological Response to Certolizumab Pegol (CLiPCert). UCB.
Carlomaurizio Montecucco - One of the best experts on this subject based on the ideXlab platform.
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use of ultrasound guided small Joint Biopsy to evaluate the histopathologic response to rheumatoid arthritis therapy recommendations for application to clinical trials
Arthritis & Rheumatism, 2015Co-Authors: Frances Humby, Stephen Kelly, Rebecca Hands, V. Rocher, Maria Dicicco, Lu Zou, Serena Bugatti, Antonio Manzo, Roberto Caporali, Carlomaurizio MontecuccoAbstract:Medical Research Council to develop the Pathobiology of Early Arthritis Cohort. Grant Number: 86661. The Clinical and Pathological Response to Certolizumab Pegol (CLiPCert). UCB.
Rebecca Hands - One of the best experts on this subject based on the ideXlab platform.
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OP0217 INVOLVEMENT OF LARGE JointS AT DISEASE PRESENTATION IS ASSOCIATED WITH DIVERSE HISTOPATHOLOGICAL FEATURES AND CLINICAL OUTCOMES IN EARLY RHEUMATOID ARTHRITIS
Annals of the Rheumatic Diseases, 2020Co-Authors: Felice Rivellese, Frances Humby, Rebecca Hands, G. Lliso Ribera, Alessandra Nerviani, E. Sciacca, Giovanni Giorli, Liliane Fossati-jimack, Georgina Thorborn, Myles LewisAbstract:Background: The involvement of large Joints at disease presentation in early Rheumatoid Arthritis (RA) has been associated with severe disease activity. At the same time, the clinical heterogeneity of RA is known to be mirrored by heterogeneity of synovial inflammation, with specific histological patterns (pathotypes) associated with treatment response and disease progression. However, it is not known whether Joint size is associated with specific pathotypes. Objectives: To analyse histopathological features of synovial biopsies from Joints of different sizes and establish the relationship with clinical outcomes in patients with early RA. Methods: 167 patients with early ( Results: The majority of synovial biopsies were performed on medium and small Joints (60.6% and 19.4%) as compared to 21.3% in large Joints (Table 1). At baseline, patients who underwent large Joint Biopsy showed significantly higher levels of inflammation (CRP 27.9±32.4 large, 20.7±26.9 medium, 10.4±9.8 small, p=0.007) and higher HAQ (1.8 ± 0.7 large, 1.4 ± 0.8 medium, 1.2 ±0.9 small, p=0.012), with no differences in DAS28. Significantly higher inflammatory scores and higher proportion of lympho-myeloid pathotype were observed in large Joints (Table 1 and Figure 1). 6 months after treat-to-target treatment with csDMARDs, large Joints patients had significantly higher HAQ and lower response (RR for low disease activity in large vs medium Joints 0.5, 95%CI 0.2-0.9, p=0.03). Finally, differentially expressed genes by RNA-seq showed segregation according to Joint size (Figure 2), with upregulation of genes of the Homeobox transcription factors family in large Joints. Conclusion: Synovial Biopsy of large Joints as the most inflamed Joints at disease presentation identified patients with early RA with specific histopathological features and clinical outcomes. Together with clustering of differentially expressed genes according to Joint size, this suggests that the involvement of different Joint compartments in early RA contributes to disease heterogeneity with potential physiopathological and clinical implications. References: [1]Humby et al Ann Rheum Dis. 2019 Jun;78(6):761-772 [2]Lewis et al Cell Rep. 2019 Aug 27;28(9):2455-2470.e5 [3]Linn-Rasker SP et al Ann Rheum Dis. 2007 May;66(5):646-50 Acknowledgments: PEAC http://www.peac-mrc.mds.qmul.ac.uk MRC grant 36661 & ARUK Grant 20022 F. Rivellese NIHR Fellowship TRF-2018-11-ST2-002 Disclosure of Interests: None declared
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use of ultrasound guided small Joint Biopsy to evaluate the histopathologic response to rheumatoid arthritis therapy recommendations for application to clinical trials
Arthritis & Rheumatism, 2015Co-Authors: Frances Humby, Stephen Kelly, Rebecca Hands, V. Rocher, Maria Dicicco, Lu Zou, Serena Bugatti, Antonio Manzo, Roberto Caporali, Carlomaurizio MontecuccoAbstract:Medical Research Council to develop the Pathobiology of Early Arthritis Cohort. Grant Number: 86661. The Clinical and Pathological Response to Certolizumab Pegol (CLiPCert). UCB.
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Use of Ultrasound‐Guided Small Joint Biopsy to Evaluate the Histopathologic Response to Rheumatoid Arthritis Therapy: Recommendations for Application to Clinical Trials
Arthritis & rheumatology (Hoboken N.J.), 2015Co-Authors: Frances Humby, Stephen Kelly, Rebecca Hands, V. Rocher, Maria Dicicco, Lu Zou, Serena Bugatti, Antonio Manzo, Roberto CaporaliAbstract:Medical Research Council to develop the Pathobiology of Early Arthritis Cohort. Grant Number: 86661. The Clinical and Pathological Response to Certolizumab Pegol (CLiPCert). UCB.
J Sieper - One of the best experts on this subject based on the ideXlab platform.
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successful treatment of active ankylosing spondylitis with the anti tumor necrosis factor α monoclonal antibody infliximab
Arthritis & Rheumatism, 2000Co-Authors: Jan Brandt, J Sieper, Hildrun Haibel, Daniel Cornely, W. Golder, Jaqueline Reddig, Wolfgang Thriene, J A Gonzalez, Jurgen BraunAbstract:Objective Tumor necrosis factor α (TNFα) has been detected in sacroiliac Joint Biopsy specimens from patients with spondylarthropathy. The present open pilot study was undertaken to test the efficacy of the anti-TNFα monoclonal antibody infliximab in the treatment of active ankylosing spondylitis (AS). Methods Eleven patients with AS of short duration (median 5 years, range 0.5–13 years) that had been active for at least 3 months (range 3–72 months) were treated with 3 infusions of infliximab (at weeks 0, 2, and 6), in a dosage of 5 mg/kg. Ten of the 11 patients had elevated C-reactive protein (CRP) levels (>6 mg/liter) before treatment; these elevations were known to have had persisted >1 year in at least 3 patients. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI), pain as measured on a visual analog scale, and the Bath AS Metrology Index (BASMI) were assessed. Quality of life was assessed using the Short Form 36 instrument. Laboratory markers of disease activity, including interleukin-6 (IL-6) levels, were determined. Dynamic magnetic resonance imaging (MRI) of the spine was performed in 5 patients. Results One patient withdrew from the study due to the occurrence of urticarial xanthoma 8 days after the first infusion. At study enrollment, 3 of 5 patients had evidence of spinal inflammation (spondylitis and spondylodiscitis) as detected by MRI; followup MRI 2–6 weeks after the third infusion revealed improvement in 2. Improvement of ≥50% in activity, function, and pain scores was documented in 9 of 10 patients; the median improvement in the BASDAI after 4 weeks was 70% (range 41–94%). This clear-cut benefit lasted for 6 weeks after the third infusion in 8 of 10 patients. The median CRP level decreased from 15.5 mg/liter (range <6–90.8) to normal, and the median IL-6 level from 12.4 mg/liter (range 0–28.4) to normal (<5). There was improvement in all 9 SF-36 concepts; the improvement was significant for 6 concepts. Conclusion These data suggest that anti-TNFα therapy is very effective for several weeks in AS. Whether this therapy, in addition to its antiinflammatory effect, prevents ankylosis remains to be determined.
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use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac Joint Biopsy specimens from patients with ankylosing spondylitis
Arthritis & Rheumatism, 1995Co-Authors: Jurgen Braun, Matthias Bollow, Lucia Neure, Eva Seipelt, Fikret Seyrekbasan, H Herbst, U Eggens, A Distler, J SieperAbstract:OBJECTIVE: To investigate mechanisms involved in inflammation and new bone formation in the sacroiliac (SI) Joints of patients with ankylosing spondylitis (AS). PATIENTS AND METHODS: Computed tomography-assisted Biopsy of the SI Joint was performed in 5 patients with AS with a mean disease duration of 4.5 years and radiographic stage 2-3 disease. Immunohistologic studies were performed with the alkaline phosphatase-anti-alkaline phosphatase technique, and cytokine messenger RNA (mRNA) was detected by in situ hybridization. RESULTS: Dense cellular infiltrates with varying amounts of CD3+ cells (mean +/- SD 53.3 +/- 24.1%), CD4+ cells (29.7 +/- 17.6%), CD8+ cells (15.8 +/- 11.4%), CD14+ cells (23.6 +/- 16.9%), CD45RO+ cells (48.4 +/- 23.6%), and CD45RA+ cells (4.5 +/- 2.9%) were found in the synovial portion of the SI Joints of all 5 patients. In these infiltrates a high amount of tumor necrosis factor alpha (TNF alpha) mRNA and, near the site of new bone formation, a lower amount of transforming growth factor beta (TGF beta) mRNA, were detected, while no message for interleukin-1 was found in the 3 patients examined by this technique. CONCLUSION: The presence of T cells and macrophages was demonstrated in cellular infiltrates in the SI Joints of 5 patients with active AS. The finding of abundant TNF alpha message in these Joints could have implications regarding potential immunotherapeutic approaches to this disease. TGF beta might be involved in new bone formation in AS.
