28 results on '"Bruchfeld A."'
Search Results
2. Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial
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Smith, Rona M, primary, Jones, Rachel B, additional, Specks, Ulrich, additional, Bond, Simon, additional, Nodale, Marianna, additional, Al-jayyousi, Reem, additional, Andrews, Jacqueline, additional, Bruchfeld, Annette, additional, Camilleri, Brian, additional, Carette, Simon, additional, Cheung, Chee Kay, additional, Derebail, Vimal, additional, Doulton, Tim, additional, Ferraro, Alastair, additional, Forbess, Lindsy, additional, Fujimoto, Shouichi, additional, Furuta, Shunsuke, additional, Gewurz-Singer, Ora, additional, Harper, Lorraine, additional, Ito-Ihara, Toshiko, additional, Khalidi, Nader, additional, Klocke, Rainer, additional, Koening, Curry, additional, Komagata, Yoshinori, additional, Langford, Carol, additional, Lanyon, Peter, additional, Luqmani, Raashid, additional, McAlear, Carol, additional, Moreland, Larry W, additional, Mynard, Kim, additional, Nachman, Patrick, additional, Pagnoux, Christian, additional, Peh, Chen Au, additional, Pusey, Charles, additional, Ranganathan, Dwarakanathan, additional, Rhee, Rennie L, additional, Spiera, Robert, additional, Sreih, Antoine G, additional, Tesar, Vladamir, additional, Walters, Giles, additional, Wroe, Caroline, additional, Jayne, David, additional, and Merkel, Peter A, additional
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- 2023
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3. AB0616 Myeloperoxidase (MPO) positive extracellular vesicles (EVs) expressing complement split products in Anti - Neutrophil Cytoplasmic Antibody (ANCA) -associated Vasculitis (AAV)
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Juto, A., primary, Mahmoud Hourani Soutari, N., additional, Taxiarchis, A., additional, Malmström, V., additional, Bruchfeld, A., additional, Antovic, A., additional, and Gunnarsson, I., additional
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- 2022
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4. Rituximab versus azathioprine for maintenance of remission for patients with ANCA-associated vasculitis and relapsing disease: an international randomised controlled trial
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Rona M Smith, Rachel B Jones, Ulrich Specks, Simon Bond, Marianna Nodale, Reem Al-jayyousi, Jacqueline Andrews, Annette Bruchfeld, Brian Camilleri, Simon Carette, Chee Kay Cheung, Vimal Derebail, Tim Doulton, Alastair Ferraro, Lindsy Forbess, Shouichi Fujimoto, Shunsuke Furuta, Ora Gewurz-Singer, Lorraine Harper, Toshiko Ito-Ihara, Nader Khalidi, Rainer Klocke, Curry Koening, Yoshinori Komagata, Carol Langford, Peter Lanyon, Raashid Luqmani, Carol McAlear, Larry W Moreland, Kim Mynard, Patrick Nachman, Christian Pagnoux, Chen Au Peh, Charles Pusey, Dwarakanathan Ranganathan, Rennie L Rhee, Robert Spiera, Antoine G Sreih, Vladamir Tesar, Giles Walters, Caroline Wroe, David Jayne, and Peter A Merkel
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Rheumatology ,Immunology ,Immunology and Allergy ,General Biochemistry, Genetics and Molecular Biology - Abstract
ObjectiveFollowing induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab.MethodsRITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse).ResultsRituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, pConclusionsFollowing induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse.Trial registration numberNCT01697267; ClinicalTrials.gov identifier
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- 2023
5. AB0616 Myeloperoxidase (MPO) positive extracellular vesicles (EVs) expressing complement split products in Anti - Neutrophil Cytoplasmic Antibody (ANCA) -associated Vasculitis (AAV)
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A. Juto, N. Mahmoud Hourani Soutari, A. Taxiarchis, V. Malmström, A. Bruchfeld, A. Antovic, and I. Gunnarsson
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Rheumatology ,Immunology ,Immunology and Allergy ,General Biochemistry, Genetics and Molecular Biology - Abstract
BackgroundComplement activation has a critical role for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We have previously shown increased expression of complement split products C3a and C5a on myeloperoxidase (MPO) positive EVs (MPO+EVs) in plasma from AAV patients with kidney involvement compared to the patients with non-renal disease and the EV-levels correlated with disease activity (1).ObjectivesTo investigate the expression of a larger set of complement components on circulating MPO+EVs in relation to disease activity and kidney involvement in patients with AAV.MethodsEighty-nine patients with AAV and 23 healthy controls were included. The concentration of MPO+EVs expressing complement split products C3a, C4d, C5a, terminal complement complex-TCC (C5b-9) or complement factor B (CFB) were analyzed from citrate plasma by flow cytometry. The assessment of vasculitis disease activity was performed using the Birmingham Vasculitis Activity Score (BVAS).ResultsIn the AAV group, there were 47 males (52.8%), the median age was 56 years and 33 (37.1%) patients were anti-MPO-positive and 54 (60.7%) were anti-PR3-positive. Two patients were positive for both antibodies. Median disease duration for patients with active AAV (BVAS>0; n=81) was 4 days and for patients in remission (BVAS 0; n=8) 1259 days. 64% had kidney involvement (n=52). Highly active AAV (BVAS ≥12) was noted in 62 patients, of whom 49 patients had kidney involvement. Active disease (0+, MPO+C3a+, MPO+C4d+ and MPO+TCC+ EVs compared to healthy controls (all p+, MPO+C4d+ and MPO+TCC+ EVs compared to healthy controls (all p≤0.001). There was a significant difference in levels of MPO+(p=0.02), MPO+C3a+(p+C4d+(p+TCC+ EVs (p0 there was a weak correlation between MPO+, MPO+C3a+, MPO+C4d+, MPO+TCC+ EVs and BVAS. Kidney biopsies from 34 patients were classified according to histopathological class (2): crescentic (n=6), focal (n=18), mixed (n=6), sclerotic (n=4). The level of MPO+C4d+EVs was higher in the sclerotic type compared to focal (p=0.04, 95% CI [2.4–103.7]) and mixed (p=0.04, 95% CI [1.4–119.1]).ConclusionLevels of EVs expressing complement split products were generally increased in AAV patients and patients with kidney involvement had higher levels of total MPO+EVs exposing C3a, C4d or TCC compared with patients without suggesting a role in kidney AAV pathogenesis. Patients with sclerotic kidney histotype had higher levels of MPO+C4d EVs compared with focal and mixed subgroups pointing to that activation of the classical complement pathway may be of importance in severe forms of kidney AAV.References[1]Antovic A et al. J Rheumatol. 2020 May 1;47(5):714-721. doi: 10.3899/jrheum.181347. Epub 2019 Aug 1. PMID: 31371653.[2]Berden AE et al. J Am Soc Nephrol. 2010 Oct;21(10):1628-36. doi: 10.1681/ASN.2010050477. Epub 2010 Jul 8. PMID: 20616173.Disclosure of InterestsNone declared
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- 2022
6. Are patients with rheumatoid arthritis still at an increased risk of tuberculosis and what is the role of biological treatments?
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Arkema, Elizabeth V, Jonsson, Jerker, Baecklund, Eva, Bruchfeld, Judith, Feltelius, Nils, Askling, Johan, Cöster, Lars, Forsblad, Helena, Geborek, Peirre, Jacobsson, Lennart, Klarskog, Lars, Kristensen, Lars-Erik, Lindblad, Staffan, Rantapää-Dahlqvist, Solbritt, and van Vollenhoven, Ronald
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- 2015
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7. POS1230 OUTCOME FOLLOWING COVID-19 INFECTION IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-ASSOCIATED VASCULITIS
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Antovic, A., primary, Lövström, B., additional, Hugelius, A., additional, Borjesson, O., additional, Bruchfeld, A., additional, and Gunnarsson, I., additional
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- 2021
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8. OP0003 AUTOREACTIVE CD4+ T CELLS AND THEIR TCR REPERTOIRE IN PR3-ANCA ASSOCIATED VASCULITIS
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Kumar, R., primary, Yoosuf, N., additional, Bartoletti, A., additional, Avik, A., additional, Raposo, B., additional, Jonasdottir, A., additional, Lövström, B., additional, Chemin, K., additional, Bruchfeld, A., additional, Gunnarsson, I., additional, and Malmström, V., additional
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- 2021
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9. Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis
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Smith, Rona M, primary, Jones, Rachel Bronwen, additional, Specks, Ulrich, additional, Bond, Simon, additional, Nodale, Marianna, additional, Aljayyousi, Reem, additional, Andrews, Jacqueline, additional, Bruchfeld, Annette, additional, Camilleri, Brian, additional, Carette, Simon, additional, Cheung, Chee Kay, additional, Derebail, Vimal, additional, Doulton, Tim, additional, Forbess, Lindsy, additional, Fujimoto, Shouichi, additional, Furuta, Shunsuke, additional, Gewurz-Singer, Ora, additional, Harper, Lorraine, additional, Ito-Ihara, Toshiko, additional, Khalidi, Nader, additional, Klocke, Rainer, additional, Koening, Curry, additional, Komagata, Yoshinori, additional, Langford, Carol, additional, Lanyon, Peter, additional, Luqmani, Raashid Ahmed, additional, Makino, Hirofumi, additional, McAlear, Carole, additional, Monach, Paul, additional, Moreland, Larry W, additional, Mynard, Kim, additional, Nachman, Patrick, additional, Pagnoux, Christian, additional, Pearce, Fiona, additional, Peh, Chen Au, additional, Pusey, Charles, additional, Ranganathan, Dwarakanathan, additional, Rhee, Rennie L, additional, Spiera, Robert, additional, Sreih, Antoine G, additional, Tesar, Vladimir, additional, Walters, Giles, additional, Weisman, Michael H, additional, Wroe, Caroline, additional, Merkel, Peter, additional, and Jayne, David, additional
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- 2020
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10. SAT0069 TUBERCULOSIS IN BIOLOGIC-NAÏVE PATIENTS WITH RHEUMATOID ARTHRITIS - RISK FACTORS AND TUBERCULOSIS CHARACTERISTICS
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Sundbaum, J., primary, Arkema, E., additional, Bruchfeld, J., additional, Jonsson, J., additional, Askling, J., additional, and Baecklund, E., additional
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- 2020
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11. POS1230 OUTCOME FOLLOWING COVID-19 INFECTION IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-ASSOCIATED VASCULITIS
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Iva Gunnarsson, A. Bruchfeld, Aleksandra Antovic, B. Lövström, A. Hugelius, and Ola Börjesson
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medicine.medical_specialty ,business.industry ,Immunology ,medicine.disease ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,Rheumatology ,Maintenance therapy ,Internal medicine ,Intensive care ,Cohort ,Prednisolone ,Immunology and Allergy ,Medicine ,Rituximab ,business ,Microscopic polyangiitis ,Granulomatosis with polyangiitis ,Anti-neutrophil cytoplasmic antibody ,medicine.drug - Abstract
Background:Patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) require immunosuppressive therapy for disease control and reduction of disease relapse and may be at risk for complications during Sars-CoV-2 (COVID-19) infection.Objectives:To analyze the consequences of COVID-19 in a large cohort of AAV patients regarding occurrence, need of hospitalization, treatment at the intensive care units (ICU), or death.Methods:Data were retrieved from March 2020 to mid-January 2021 from medical records from the AAV cohort (n=233). Patients diagnosed with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA) were included. Data included age, gender, diagnosis, ongoing immunosuppressive medication at onset of COVID-19 or at last follow-up in non-COVID individuals. Renal involvement (ever) and estimated glomerular filtration rate (eGFR) were included. COVID-19 was confirmed either by a positive PCR test in the upper airways or by serology. Severe COVID-19 was defined as need of non-invasive ventilation, ICU care, and/or death.Results:The cohort comprised of 172 patients with GPA, 50 with MPA and 11 with EGPA. There were 121 females (52%). During the study period, 20 patients (8.6%) were diagnosed with COVID-19. The median age at data retrieval in all patients was 68 years (21-93), in the COVID-19 group 63 (29-93) and 68.5 (21-90) years in the non-COVID patients.Fourty-three patients in all (18%) were hospitalized during the study period of which 11 (4.7%) due to COVID-19 infection. In all, 8 deaths occurred of which 3 were related to COVID-19.At data retrieval, 110 (47%) patients were on prednisolone treatment, 10/20 (50%) in the COVID-19 group and 100 (47%) in the non-COVID-19 group (p=0.5), with significantly higher doses in COVID-19 patients (pOf the 20 COVID-19 cases, 8 had severe COVID-19. Of these, 2 were inactive without immunosuppressive treatment, 4 had stable disease with prednisolone (5-7.5 mg/day) in combination with DMARDs, and 2 were active treated with high dose prednisolone (25-50 mg/day) in combination with cyclophosphamide and rituximab (n=1) or rituximab (n=1).A higher proportion of patients had active AAV (p=0.03) in the severe COVID-19 then in the non-COVID group (10/213 patients).In the group with the severe COVID-19, 1/8 (12%) patient had rituximab as maintenance therapy, compared to 61/213 (28.6%) in the group of non-COVID-19 patients (p=0.5).Renal involvement (ever) was present in 144 patients (62%), in 6 patients (30%) with COVID- 19, from which 5 (62%) were in the group of severe COVID-19 patients. Median eGFR did not differ between severe COVID-19 and remaining patients with renal involvement independently of COVID-19 infection.Conclusion:We found a high rate of severe COVID-19 infection in our cohort of AAV patients which indicates risk for serious complications, especially in patients with active disease and intense immunosuppressive therapy. Maintenance therapy with rituximab did not seem to increase the risk for severe COVID-19. The findings stress the need for continued shielding and early vaccination in AAV patients.Disclosure of Interests:None declared
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- 2021
12. OP0003 AUTOREACTIVE CD4+ T CELLS AND THEIR TCR REPERTOIRE IN PR3-ANCA ASSOCIATED VASCULITIS
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Rajesh Kumar, Annette Bruchfeld, Iva Gunnarsson, Niyaz Yoosuf, Karine Chemin, Bruno Raposo, Björn Lövström, Asta Jonasdottir, V Malmström, A. Bartoletti, and Aune Avik
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business.industry ,medicine.medical_treatment ,T cell ,Immunology ,T-cell receptor ,Autoantibody ,General Biochemistry, Genetics and Molecular Biology ,Cytokine ,medicine.anatomical_structure ,Immunophenotyping ,Immune system ,Rheumatology ,Antigen ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,business - Abstract
Background:ANCA-associated vasculitis (AAV) with proteinase 3 (PR3) ANCA is genetically associated with HLA-DP [1], is often relapsing in nature, and has a predisposition for kidneys, lungs and ear-nose-throat involvement [2]. Despite the presence of PR3+ANCA, indicating CD4+T-cell help in the disease, the knowledge about autoreactive CD4+T cells is scarce. Activated T cells have been shown at site of inflammation [3] and involvement of proinflammatory cytokines in circulation is also reported [4, 5].Objectives:Identification of autoreactive T cells may help to identify the drivers of the immune responses and chronicity. We therefore aimed to investigate PR3-specific CD4+T-cell responses in peripheral blood of AAV patients with a focus on both phenotype and T-cell receptor (TCR) repertoires.Methods:The study included sixty-six patients: 26 with active PR3 autoantibody+ AAV, 21 with inactive but PR3+ AAV and 19 with inactive PR3- AAV. In-vitro cultures with PR3 protein were established to assess antigen-specific cytokine responses in a 3-color fluorospot assay. Deep immunophenotyping was performed by flow cytometry. Antigen-responsive CD4+ T cells were isolated and single cell TCRαβ sequences were generated and analyzed from PR3+ AAV patients (n=5) using a previously published protocol [6].Results:PBMCs from AAV patients demonstrated an HLA-DP associated cytokine responses to PR3 stimulation including IFN-γ and IL-10, but not IL-17A. This T-cell autoreactivity was found to be confined to a highly differentiated CD4+ T cell population characterized by perforin and GPR56 expression, implicating a cytotoxic feature of the response. Active disease involved a reduction in expression of several markers associated with cytotoxicity amongst the CD4+GPR56+ T cells. Their frequency was also negatively associated with the doses of prednisolone. A similar phenotype was shared with T cells activated by human cytomegalovirus (HCMV) peptides in the same patient cohort. Single cell sequencing of paired alpha beta T-cell receptors (TCRs) revealed different patterns of gene usage between PR3 and HCMV reactive T cells. Moreover, we could identify shared (public) PR3-reactive T-cell clones between different HLA-DPB1*04:01+ patients.Conclusion:PR3 is an autoantigen which provokes ANCA responses in AAV patients. Our study identified PR3-reactive CD4+ T cells at the level of their phenotype and TCR repertoire. The autoreactive CD4+ T cells, present in both active and inactive disease, implicate chronic antigen exposure and the persistence of long-lived T-cell clones. The presence of public autoreactive clones between HLA-DPB1*04:01+ patients suggests an active role for these cells in pathogenesis of AAV and validates the link with predisposed genotype.References:[1]Lyons PA, Rayner TF, Trivedi S, Holle JU, Watts RA, Jayne DR, et al. Genetically distinct subsets within ANCA-associated vasculitis. New England Journal of Medicine. 2012; 367(3):214-223.[2]Kumar Sharma R, Lövström B, Gunnarsson I, Malmström V. Proteinase 3 autoreactivity in Anti-Neutrophil Cytoplasmic Antibody-associated vasculitis–immunological versus clinical features. Scandinavian Journal of Immunology. 2020:e12958.[3]Wilde B, Thewissen M, Damoiseaux J, van Paassen P, Witzke O, Tervaert JWCJAr, et al. T cells in ANCA-associated vasculitis: what can we learn from lesional versus circulating T cells? 2010; 12(1):204.[4]Hoffmann JC, Patschan D, Dihazi H, Müller C, Schwarze K, Henze E, et al. Cytokine profiling in anti neutrophil cytoplasmic antibody-associated vasculitis: a cross-sectional cohort study. Rheumatology international. 2019; 39(11):1907-1917.[5]Berti A, Warner R, Johnson K, Cornec D, Schroeder D, Kabat B, et al. Circulating Cytokine Profiles and ANCA Specificity in Patients with ANCA-Associated Vasculitis. Arthritis & rheumatology (Hoboken, NJ). 2018; 70(7):1114.[6]Han A, Glanville J, Hansmann L, Davis MM. Linking T-cell receptor sequence to functional phenotype at the single-cell level. Nature biotechnology. 2014; 32(7):684-692.Disclosure of Interests:None declared
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- 2021
13. Deoxyspergualin in relapsing and refractory Wegener’s granulomatosis
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Flossmann, O, Baslund, B, Bruchfeld, A, Tervaert, J W Cohen, Hall, C, Heinzel, P, Hellmich, B, Luqmani, R A, Nemoto, K, Tesar, V, and Jayne, D R W
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- 2009
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14. SAT0069 TUBERCULOSIS IN BIOLOGIC-NAÏVE PATIENTS WITH RHEUMATOID ARTHRITIS - RISK FACTORS AND TUBERCULOSIS CHARACTERISTICS
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Johan Askling, Eva Baecklund, Judith Bruchfeld, Johanna Karlsson Sundbaum, Jerker Jonsson, and Elizabeth V. Arkema
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0301 basic medicine ,medicine.medical_specialty ,Tuberculosis ,Immunology ,Population ,Tuberculin ,Context (language use) ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Immunology and Allergy ,Medicine ,education ,030203 arthritis & rheumatology ,education.field_of_study ,business.industry ,Odds ratio ,medicine.disease ,Obstructive lung disease ,030104 developmental biology ,Rheumatoid arthritis ,Prednisolone ,business ,medicine.drug - Abstract
Background:The risk of tuberculosis (TB) has decreased in biologic disease modifying anti-rheumatic drugs (bDMARDs) treated rheumatoid arthritis (RA) patients, but remains unaltered 4-fold increased in bio-naïve RA patients compared to the general population in Sweden (1). In absolute numbers, most TB cases in contemporary RA patients occur in the group of bio-naïve patients. Knowledge about risk factors for TB and TB characteristics in bio-naïve RA patients is still limited.Objectives:To investigate risk factors for TB and TB characteristics in bio-naïve RA patients.Methods:Population-based case-control study. A national bio-naïve RA cohort was identified from the National Patient Register and the Swedish Rheumatology Quality Register. RA cases with TB were identified by linkage to the Swedish Tuberculosis Register (with mandatory TB registration) 2001-2014 (n=42). For each case, four matched RA controls without TB were identified. Clinical data were obtained from medical records. Univariate and multivariable logistic regression analyses were used to estimate risk for TB expressed as adjusted (adj) odds ratio (OR) with 95% confidence intervals (CI).Results:After review of the medical records and validation of diagnoses, 31 cases with RA and TB and 122 controls remained in the study. The TB cases had a median of 3 (1-6) reported TB risk factors, and almost 90% were born before 1950. Only one case was screened for TB (with negative result of tuberculin skin test). Active TB occurred at a mean of 15 years after RA diagnosis, and all except three cases were considered as reactivation of latent TB. Exposure to leflunomide (5 cases, 4 controls) (adj OR 6.02; 95% CI 1.47-24.65) and azathioprine (5 cases, 6 controls) (adj OR 3.85; 95% CI 1.06-13.79) were associated with increased risk for TB. Methotrexate, used in 67.7% of cases and 73.9% of controls, was not associated with increased risk of TB (adj OR 0.83; 95% CI 0.34-1.98). Exposure to corticosteroids was more common among cases than controls (74.2% vs 53.8%, p= 0.04), and was associated with an adj OR for TB of 2.44 (95% CI 1.00-5.92). No significant differences were identified between prednisolone-treated cases and controls in terms of maximum dose ever of prednisolone, treatment duration before TB, or cumulative dose of prednisolone during the last year before diagnosis of TB. Obstructive pulmonary disease was the only comorbidity linked to an increased TB risk (adj OR 3.94; 95% CI 1.45-10.69). Pulmonary TB dominated (84%) followed by TB lymphadenitis (19%). Treatment success was 94%, comparable to TB patients in general.Conclusion:Several RA-associated risk factors may contribute to increased TB risk in bio-naïve RA patients (treatment with leflunomide, azathioprine, or prednisolone and concomitant obstructive lung disease). We could not confirm previous findings of an association with the use of moderate to high doses of prednisolone (≥15 mg). TB risk seems difficult to predict with precision in the individual bio-naïve patient based on RA-associated risk factors. To further decrease the TB risk in RA patients TB screening should also be considered in the group of bio-naïve patients.References:[1] Arkema EV et al. Are patients with rheumatoid arthritis still at an increased risk of tuberculosis and what is the role of biological treatments? Ann Rheum Dis 2015;74:1212-17.Disclosure of Interests:Johanna Sundbaum: None declared, Elizabeth Arkema: None declared, Judith Bruchfeld: None declared, Jerker Jonsson: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma, Eva Baecklund: None declared
- Published
- 2020
15. Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial
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Thomas F. Hiemstra, Janak de Zoysa, David Jayne, Jose Ballarin, Augusto Vaglio, Paul A. Brogan, Karen Dahlsveen, Rachel B Jones, Chen Au Peh, Annette Bruchfeld, Daniel Engelbert Blockmans, D Walsh, Giles Walters, Michael Walsh, Peter Lanyon, Maria C. Cid, Georgina Espígol-Frigolé, Lorraine Harper, Vladimir Tesar, Hiemstra, Thomas [0000-0002-2115-8689], Jayne, David [0000-0002-1712-0637], and Apollo - University of Cambridge Repository
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Adult ,Male ,medicine.medical_specialty ,Cyclophosphamide ,Adolescent ,Immunology ,030232 urology & nephrology ,Azathioprine ,Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ,Rate ratio ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Randomized controlled trial ,law ,Recurrence ,Internal medicine ,Clinical endpoint ,Immunology and Allergy ,Medicine ,Humans ,Child ,Anti-neutrophil cytoplasmic antibody ,mycophenolate ,030203 arthritis & rheumatology ,business.industry ,induction therapy ,Induction Chemotherapy ,Mycophenolic Acid ,medicine.disease ,randomised trial ,Regimen ,Treatment Outcome ,Female ,business ,Vasculitis ,ANCA-associated vasculitis ,Immunosuppressive Agents ,medicine.drug - Abstract
ObjectivesCyclophosphamide induction regimens are effective for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but are associated with infections, malignancies and infertility. Mycophenolate mofetil (MMF) has shown high remission rates in small studies of AAV.MethodsWe conducted a randomised controlled trial to investigate whether MMF was non-inferior to cyclophosphamide for remission induction in AAV. 140 newly diagnosed patients were randomly assigned to MMF or pulsed cyclophosphamide. All patients received the same oral glucocorticoid regimen and were switched to azathioprine following remission. The primary endpoint was remission by 6 months requiring compliance with the tapering glucocorticoid regimen. Patients with an eGFR ResultsAt baseline, ANCA subtype, disease activity and organ involvement were similar between groups. Non-inferiority was demonstrated for the primary remission endpoint, which occurred in 47 patients (67%) in the MMF group and 43 patients (61%) in the cyclophosphamide group (risk difference 5.7%, 90% CI −7.5% to 19%). Following remission, more relapses occurred in the MMF group (23 patients, 33%) compared with the cyclophosphamide group (13 patients, 19%) (incidence rate ratio 1.97, 95% CI 0.96 to 4.23, p=0.049). In MPO-ANCA patients, relapses occurred in 12% of the cyclophosphamide group and 15% of the MMF group. In PR3-ANCA patients, relapses occurred in 24% of the cyclophosphamide group and 48% of the MMF group. Serious infections were similar between groups (26% MMF group, 17% cyclophosphamide group) (OR 1.67, 95% CI 0.68 to 4.19, p=0.3).ConclusionMMF was non-inferior to cyclophosphamide for remission induction in AAV, but resulted in higher relapse rate.Trial registration numberNCT00414128.
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- 2018
16. Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial
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Jones, Rachel B, primary, Hiemstra, Thomas F, additional, Ballarin, Jose, additional, Blockmans, Daniel Engelbert, additional, Brogan, Paul, additional, Bruchfeld, Annette, additional, Cid, Maria C, additional, Dahlsveen, Karen, additional, de Zoysa, Janak, additional, Espigol-Frigolé, Georgína, additional, Lanyon, Peter, additional, Peh, Chen Au, additional, Tesar, Vladimir, additional, Vaglio, Augusto, additional, Walsh, Michael, additional, Walsh, Dorothy, additional, Walters, Giles, additional, Harper, Lorraine, additional, and Jayne, David, additional
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- 2019
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17. Are patients with rheumatoid arthritis still at an increased risk of tuberculosis and what is the role of biological treatments?
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Johan Askling, Elizabeth V. Arkema, Eva Baecklund, Nils Feltelius, Judith Bruchfeld, and Jerker Jonsson
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Adult ,Male ,medicine.medical_specialty ,Tuberculosis ,Immunology ,Antibodies, Monoclonal, Humanized ,Receptors, Tumor Necrosis Factor ,General Biochemistry, Genetics and Molecular Biology ,Etanercept ,Arthritis, Rheumatoid ,Cohort Studies ,Rheumatology ,Risk Factors ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,In patient ,Aged ,Proportional Hazards Models ,Sweden ,Biological Products ,Tumor Necrosis Factor-alpha ,business.industry ,Adalimumab ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Infliximab ,Increased risk ,Antirheumatic Agents ,Case-Control Studies ,Immunoglobulin G ,Rheumatoid arthritis ,Female ,business - Abstract
ObjectiveTo estimate the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) both with and without exposure to biological therapy and to directly compare the risks between therapies.MethodsData from the Swedish National Population Registers, Tuberculosis Register and the Swedish Biologics Register were used to conduct a prospective population-based national cohort study (2002–2011). We estimated the rate of incident TB in the general population and in a cohort of biological-naïve and biological-exposed patients diagnosed with RA. Cox models were used to estimate HRs with particular attention to risks by calendar and follow-up time and individual biologics.ResultsCompared to the general population, RA patients not exposed to biologicals had a fourfold increased risk of TB (HR 4.2; 95% CI 2.7 to 6.7), which did not decline over calendar time. In contrast, the risk of TB in the biological-exposed RA population decreased since 2002 compared with biological-naïve; from HR=7.9 (95% CI 3.3 to 18.9) in 2002–2006 to HR=2.4 (95% CI 0.9 to 6.1) in 2007–2011. The HRs for most recent exposure to adalimumab and infliximab compared with etanercept were 3.1 (95% CI 0.8 to 12.5) and 2.7 (95% CI 0.7 to 10.9), respectively, and the HR for etanercept compared with biological-naïve RA was 1.7 (95% CI 0.6 to 4.6).ConclusionsIn the past decade, the risk of TB has decreased among biological-exposed RA patients but remains higher than in biological-naïve RA patients. Most cases of TB in RA occur in biological-naïve RA patients, underscoring the elevated risk also in these patients.
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- 2014
18. Deoxyspergualin in relapsing and refractory Wegener's granulomatosis
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B Hellmich, D. R. W. Jayne, Raashid Luqmani, P Heinzel, Annette Bruchfeld, J. W. Cohen Tervaert, K Nemoto, Oliver Flossmann, Vladimir Tesar, Bo Baslund, and Christopher Hall
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Adult ,Male ,medicine.medical_specialty ,Cyclophosphamide ,Gusperimus ,medicine.medical_treatment ,Immunology ,Guanidines ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,Rheumatology ,Refractory ,Recurrence ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Prospective Studies ,Aged ,business.industry ,Remission Induction ,Granulomatosis with Polyangiitis ,Middle Aged ,medicine.disease ,Surgery ,Discontinuation ,Treatment Outcome ,Immunosuppressive drug ,Prednisolone ,Female ,Methotrexate ,business ,Vasculitis ,Immunosuppressive Agents ,medicine.drug - Abstract
OBJECTIVES: Conventional therapy of Wegener's granulomatosis with cyclophosphamide and corticosteroids is limited by incomplete remissions and a high relapse rate. The efficacy and safety of an alternative immunosuppressive drug, deoxyspergualin, was evaluated in patients with relapsing or refractory disease. METHODS: A prospective, international, multicentre, single-limb, open-label study. Entry required active Wegener's granulomatosis with a Birmingham vasculitis activity score (BVAS) > or =4 and previous therapy with cyclophosphamide or methotrexate. Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status. Deoxyspergualin, 0.5 mg/kg per day, was self-administered by subcutaneous injection in six cycles of 21 days with a 7-day washout between cycles. Cycles were stopped early for white blood count less than 4000 cells/mm(3). The primary endpoint was complete remission (BVAS 0 for at least 2 months) or partial remission (BVAS or = grade 3) treatment-related adverse events occurred in 24 (53%) patients mostly due to leucopaenias. CONCLUSIONS: Deoxyspergualin achieved a high rate of disease remission and permitted prednisolone reduction in refractory or relapsing Wegener's granulomatosis. Adverse events were common but rarely led to treatment discontinuation.
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- 2008
19. URINARY INTERLEUKIN (IL)-16 IN ANTI - NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-ASSOCIATED VASCULITIS WITH KIDNEY INVOLVEMENT.
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Juto, A., Faustini, F., Häyry, A., Larsson, A., Malmström, V., Bruchfeld, A., Antovic, A., Oke, V., and Gunnarsson, I.
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- 2023
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20. ANALYSIS OF THE PLASMA PROTEOME PROVIDES MECHANISTIC INSIGHTS INTO THE PATHOPHYSIOLOGY OF ANCA-ASSOCIATED VASCULITIS.
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Hellbacher, E., Van Hoef, V., Johansson, A., Knight, A., Gunnarsson, I., Bruchfeld, A., Eriksson, P., Olsson, S., Mohammad, A. J., Soderbergh, A., Berglin, E., Dahlqvist, S. Rantapää, and Dahlqvist, J.
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- 2023
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21. IN-DEPTH ANALYSIS OF DISEASE MANIFESTATIONS IN ANCA-ASSOCIATED VASCULITIDES IDENTIFIES DISTINCT CLINICAL PHENOTYPES, EMPHASIZING THE IMPACT OF SEX AND AGE AT DIAGNOSIS.
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Lindberg, H., Dahlqvist, S. Rantapää, Norling, O., Hellbacher, E., Berglin, E., Stegmayr, B., Baslund, B., Palm, Ø., Haukeland, H., Gunnarsson, I., Bruchfeld, A., Segelmark, M., Olsson, S., Mohammad, A. J., Svärd, A., Pullerits, R., Herlitz, H., Soderbergh, A., Eriksson, P., and Knight, A.
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- 2023
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22. OP0227 Oral C5a Receptor Antagonist CCX168 Phase 2 Clinical TRIAL in Anca-Associated Renal Vasculitis
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Jayne, D.R., primary, Bruchfeld, A., additional, Schaier, M., additional, Ciechanowski, K., additional, Harper, L., additional, Jadoul, M., additional, Segelmark, M., additional, Selga, D., additional, Szombati, I., additional, Venning, M., additional, Hugo, C., additional, Van Daele, P.L., additional, Viklicky, O., additional, Potarca, A., additional, Schall, T.J., additional, and Bekker, P., additional
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- 2014
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23. Are patients with rheumatoid arthritis still at an increased risk of tuberculosis and what is the role of biological treatments?
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Arkema, Elizabeth V, primary, Jonsson, Jerker, additional, Baecklund, Eva, additional, Bruchfeld, Judith, additional, Feltelius, Nils, additional, and Askling, Johan, additional
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- 2014
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24. OP0227 Oral C5a Receptor Antagonist CCX168 Phase 2 Clinical TRIAL in Anca-Associated Renal Vasculitis
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K. Ciechanowski, Antonia Potarca, Istvan Szombati, O. Viklicky, D. R. W. Jayne, P L A van Daele, M. Venning, Pirow Bekker, Christian Hugo, Lorraine Harper, Michel Jadoul, M. Schaier, Annette Bruchfeld, Daina Selga, T. J. Schall, and Mårten Segelmark
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medicine.medical_specialty ,Creatinine ,Cyclophosphamide ,business.industry ,Urinary system ,Immunology ,Antagonist ,Phases of clinical research ,Renal function ,medicine.disease ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,Surgery ,chemistry.chemical_compound ,Rheumatology ,chemistry ,Prednisone ,Internal medicine ,medicine ,Immunology and Allergy ,business ,Vasculitis ,medicine.drug - Abstract
Background In ANCA vasculitis, the anaphylatoxin C5a amplifies neutrophil influx and activation through C5aR. CCX168, an oral specific C5aR antagonist, is in clinical development for ANCA-associated renal vasculitis (AARV). Objectives A Phase 2 clinical trial was conducted to investigate the potential of CCX168 to contribute to disease remission and permit glucocorticoid reduction or avoidance in patients with active AARV receiving cyclophosphamide (CYC). Methods This randomized, double-blind, placebo-controlled Phase 2 trial was performed in a stepwise manner. In Step 1 (N=12), CCX168+CYC+low dose prednisone (20 mg/day starting dose) was compared to standard-of-care (SOC) (CYC+high dose prednisone, 60 mg/day starting dose). In Step 2 (N=14), CCX168+CYC and no prednisone was compared to SOC. Eligible patients had GPA, MPA, or renal limited vasculitis, were PR3 or MPO-ANCA positive, and had active renal vasculitis with a GFR >30ml/min. The dose of CCX168 was 30 mg BID PO for 12 weeks and the dose of CYC was 15 mg/kg IV q2-3 wks. Results Baseline characteristics and efficacy results at Week 12 are shown in the table. The number of steroid rescue events was not higher in the CCX168 groups compared to SOC. The incidence of renal remission was higher in the CCX168 groups compared to the SOC control group. The percent decrease from baseline in BVAS, urinary ACR and urinary MCP-1/creatinine was higher in the CCX168 groups compared to SOC. Renal function, as measured by eGFR, increased in all 3 groups, with the largest increase (6.8 mL/min/1.73 m2) in the CCX168+low dose steroids group. CCX168 appeared to be well tolerated. No unexpected serious adverse reactions were observed with CCX168 use. There was one early withdrawal from study, in the control, SOC, group. Conclusions CCX168 plus CYC appear to be at least as effective, if not more effective, as full dose steroids plus CYC in treatment of patients with an ANCA associated renal vasculitis flare. Disclosure of Interest D. Jayne Consultant for: ChemoCentryx, Inc., A. Bruchfeld Consultant for: ChemoCentryx, Inc., M. Schaier: None declared, K. Ciechanowski: None declared, L. Harper Consultant for: ChemoCentryx, Inc., M. Jadoul: None declared, M. Segelmark Consultant for: ChemoCentryx, Inc., D. Selga: None declared, I. Szombati: None declared, M. Venning Consultant for: ChemoCentryx, Inc., C. Hugo: None declared, P. Van Daele: None declared, O. Viklicky: None declared, A. Potarca Consultant for: ChemoCentryx, Inc., T. Schall Shareholder of: ChemoCentryx, Inc., Employee of: ChemoCentryx, Inc., P. Bekker Shareholder of: ChemoCentryx, Inc., Employee of: ChemoCentryx, Inc. DOI 10.1136/annrheumdis-2014-eular.3728
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- 2014
25. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up
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Harper, Lorraine, primary, Morgan, Matthew D, additional, Walsh, Michael, additional, Hoglund, Peter, additional, Westman, Kerstin, additional, Flossmann, Oliver, additional, Tesar, Vladimir, additional, Vanhille, Phillipe, additional, Groot, Kirsten de, additional, Luqmani, Raashid, additional, Flores-Suarez, Luis Felipe, additional, Watts, Richard, additional, Pusey, Charles, additional, Bruchfeld, Annette, additional, Rasmussen, Niels, additional, Blockmans, Daniel, additional, Savage, Caroline O, additional, and Jayne, David, additional
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- 2011
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26. Deoxyspergualin in relapsing and refractory Wegener's granulomatosis
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Flossmann, O, primary, Baslund, B, additional, Bruchfeld, A, additional, Cohen Tervaert, J W, additional, Hall, C, additional, Heinzel, P, additional, Hellmich, B, additional, Luqmani, R A, additional, Nemoto, K, additional, Tesar, V, additional, and Jayne, D R W, additional
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- 2008
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27. Pulse versus daily oral cyclophosphamide for induction of remission in ANCA-associated vasculitis: long-term follow-up.
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Harper, Lorraine, Morgan, Matthew D., Walsh, Michael, Hoglund, Peter, Westman, Kerstin, Flossmann, Oliver, Tesar, Vladimir, Vanhille, Phillipe, de Groot, Kirsten, Luqmani, Raashid, Flores-Suarez, Luis Felipe, Watts, Richard, Pusey, Charles, Bruchfeld, Annette, Rasmussen, Niels, Blockmans, Daniel, Savage, Caroline O., and Jayne, David
- Abstract
Introduction The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies- associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L et al Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study. Methods Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised. Results Median duration of follow-up was 4.3 years (IQR, 2.95-5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs. Discussion Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial. [ABSTRACT FROM AUTHOR]
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- 2012
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28. Correspondence on 'EULAR recommendations for the management of systemic lupus erythematosus: 2023 update' by Fanouriakis et al .
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Kronbichler A, Anders HJ, Frangou E, Mirioglu S, Odler B, Quintana LF, Soler Romeo MJ, and Bruchfeld A
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- Humans, Rheumatology standards, Immunosuppressive Agents therapeutic use, Lupus Erythematosus, Systemic drug therapy, Lupus Erythematosus, Systemic therapy, Practice Guidelines as Topic
- Abstract
Competing Interests: Competing interests: None declared.
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- 2024
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